SUBJECT INFORMATION AND INFORMED CONSENT FORM AND AUTHORIZATION TO DISCLOSE HEALTH INFORMATION Deerfield Ave, Suite 201 Lansdowne, VA 20176

Transcription

1 Gilead Sciences, Inc. / Protocol Number GS-US Page 1 of 28 SUBJECT INFORMATION AND INFORMED CONSENT FORM AND AUTHORIZATION TO DISCLOSE HEALTH INFORMATION Principal Investigator: (Study Doctor) Institution Address: Phone Number: Additional Contact(s): (Study Staff) Study Sponsor: Protocol Title: Protocol Number: Satinder Gill, M.D. Emeritas Research Group LLC Deerfield Ave, Suite 201 Lansdowne, VA (703) (24 Hours) Robert Baker Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA 94404, U.S.A. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects with Compensated Cirrhosis due to Nonalcoholic Steatohepatitis (NASH) GS-US WHAT IS A CLINICAL RESEARCH STUDY? You have been asked to take part in a clinical research study. This study will test an experimental drug named selonsertib for the treatment of advanced fibrosis of the liver due to Non-Alcoholic Steatohepatitis (NASH). Fibrosis means scarring, and it is often the end result of a disease or injury. An experimental drug is one that is currently being tested. It has not been approved by the Food and Drug Administration (FDA) for sale in the United States or by any regulatory authorities in any country in the world. Experimental drugs like selonsertib may be tested in research studies such as this one. This Subject Information and Informed Consent Form will explain the study to you. Your study doctor or study nurse will go over this form with you. Your study doctor or study nurse will answer all questions you have about the information in this form. You should understand the purpose of the study, how taking part may help you, any potential risks to you and what is expected of you during the study. If you agree to take part, you will be asked to sign and date this form. You will be given a signed and dated copy to keep. No one can force you to take part in this study. Even if you

2 Gilead Sciences, Inc. / Protocol Number GS-US Page 2 of 28 agree to take part now, you can change your mind and stop at any time without penalty or loss of benefits to which you would otherwise be entitled. WHAT IS THE PURPOSE OF THIS STUDY? You have been asked to participate in this study because you have liver cirrhosis as a result of NASH. NASH is a disease that results when fat accumulates in the liver. The body s immune system responds to the fat by attacking the liver cells. In time, enough liver cells are damaged that scar tissue forms (fibrosis) within the liver where the healthy cells used to be. When enough scarring is present, the liver is said to be cirrhotic. A cirrhotic liver is at risk for failing. NASH does not cause any symptoms even when the liver is cirrhotic. It is only once the liver begins to fail that symptoms appear. Once symptoms appear, the only known treatment is liver transplantation (removing the damaged liver and replacing it with a healthy one from someone else). It used to be believed that once cirrhosis developed, it could never be fixed. But scientists have discovered that this may not be the case. Selonsertib is being developed to reduce inflammation and fibrosis in the liver. The purpose of this study is to see if selonsertib is safe, well tolerated, and whether it can reduce fibrosis and associated complications in subjects with cirrhosis due to NASH. HOW DOES THIS STUDY WORK? If you agree to take part in this study, you will be one of 800 subjects in this study. This study will take place at about 430 sites worldwide. This study is open to male and female subjects, 18 to 70 years of age, who meet the study requirements. Your study doctor has asked you to come to the clinic for a screening visit to see if you are able to take part. This is a randomized, double-blind, placebo-controlled study. You cannot choose which group you are in. If you agree to take part in this study and meet all of the requirements, you will be randomized to one of the following three study treatment groups: Group A: 240 wes of selonsertib 6 mg tablet + placebo 18 mg tablet once daily Group B: 240 wes of selonsertib 18 mg tablet + placebo 6 mg tablet once daily Group C: 240 wes of placebo 6 mg tablet + placebo 18 mg tablet once daily Randomized means the study drug you take will be chosen by chance, like flipping a coin to receive one of the three study treatments. You will have 2 out of 5 chances (40%) of being assigned to Group A, 2 out of 5 chances (40%) of being assigned to Group B, and 1 out of 5 chances (20%) of being assigned to Group C. Placebo-controlled means that you may be taking a tablet with no medicine in it but looks like selonsertib. Double-blind means you and your study doctor will not know what study drug you will be taking. Two different doses of selonsertib are being studied because the right dose is not yet known.

3 Gilead Sciences, Inc. / Protocol Number GS-US Page 3 of 28 Selonsertib and placebo will be supplied to your study doctor by Gilead Sciences, Inc., which is the Sponsor of this study. HOW LONG WILL YOU BE ON THE STUDY? Taking part in this study will last about 240 wes (a little longer than 4 ½ years), not including the screening visit, post-study-treatment Follow-Up visit (4 wes after last dose) and Telephone Follow-Up visit (12 wes after the 240 visit). During this time, you will be required to visit the clinic at least 32 times. WHAT ARE YOUR RESPONSIBILITIES? If you decide to take part in this study, there are some rules you must follow. Some of the rules are listed below. There could be other rules that your study doctor will review with you. You must not get pregnant or get someone pregnant during this study. It is very important that you tell your study doctor all of the information you know about your health and medications or supplements you are taking now or start taking while in the study. If you do not tell the study doctor everything you know, you may be putting your health at risk. You cannot skip doses of study drug. It is important that doses be taken on time. You are not allowed to take the following medications while in this study: Disallowed 2 wes prior to Day 1 through the end of study treatment phenobarbital, phenytoin, carbamazepine, oxcarbazepine rifampin, rifabutin, rifapentine St. John s Wort, Echinacea, milk thistle (silymarin), Chinese herb sho-saikoto (or iao-shai-hu-tang) Disallowed 30 days prior to Day 1 through the end of study treatment Chronic systemic corticosteroids, tacrolimus, sirolimus, cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate obeticholic acid, elafibranor, and cenicriviroc There may be additional medications or supplements that should be used with caution that can be discussed with your study doctor. You must bring back all unused study drug and all study drug containers (even if they are empty or used). You must follow all instructions given to you while you are taking part in this study. If you do not, you may no longer be able to take part in the study. If you are unsure about what you are supposed to do, ask your study doctor.

4 Gilead Sciences, Inc. / Protocol Number GS-US Page 4 of 28 Some insurance companies require people who are renewing a policy or getting a new policy to tell them about participating in a clinical study. You should check with your insurer to determine if taking part in this study will affect your existing insurance policy. WHAT WILL HAPPEN AT EACH STUDY VISIT? The study is made up of the following parts: Screening: One or more visits to your study doctor The screening period may last up to 8 wes before the study drug is given to you. Your study doctor will review the study with you and answer any questions you may have. If you agree to take part in this study, no study-related procedures can start until this form is signed and dated. Your study doctor will also ask whether you are willing to participate in optional genomic research to test for genetic markers of disease. If you decide you do not want to take part in genomic research, you can still take part in the main study. After you have signed and dated this consent form (indicating that you understand and agree to take part in this study), your study doctor will review your medical history and the medications you are currently taking. You will be asked to participate in screening tests and procedures as described in detail in the tables below. These will help your study doctor decide if you are eligible to take part in this study. They include a complete physical exam, measurement of your vital signs, blood collection, urine drug test, a serum pregnancy test (if you are a female who can have children), an electrocardiogram (ECG), liver biopsy, and review of adverse events and concomitant medications. You will need to fast for approximately 8 hours (no food or drink, except water) prior to the screening visit so that a fasting blood sample can be collected. If your study doctor finds that you qualify for the study and you agree to continue, your first visit (Baseline/Day1) will be scheduled. If the results of the screening tests show that you do not qualify for the study, you will not be allowed to participate even if you want to. Screening information from another Gilead Sciences Phase 3 study with selonsertib (GS-US ) may be used to determine eligibility and fulfill screening visit assessments for this study. Study Treatment Phase: Thirty visits to your study doctor (Baseline/Day1, 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60,72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240). The Study Treatment Phase consists of the Randomized and Open-Label Phase.

5 Gilead Sciences, Inc. / Protocol Number GS-US Page 5 of 28 You will return to the study site at Baseline/Day 1 for your first study visit. During this visit your study doctor will confirm that you are still eligible to participate in the trial. If you are, you will be randomized to your study treatment. During your study visits, your study doctor will ask you about any medications you are taking or have taken since your last study visit. You will also be asked whether you have experienced any changes in your health (illnesses or health problems). You will undergo a series of tests and procedures which are described in detail in the tables below. Different tests and procedures are performed at different visits, but can include completion of questionnaires, a physical exam, measurement of your vital signs, blood and urine collection, a urine pregnancy test (if you are a female who can have children), an electrocardiogram (ECG), and liver biopsy. You will need to fast for approximately 8 hours prior to all study visits. You will receive your first dose of study drug(s) at your Baseline/Day 1 visit. After this you will be responsible for taking study drug tablets daily. You should take the study drug(s) once daily approximately the same time each day. If you have consented to optional genomic research a single blood sample will be drawn at the Day 1 visit and at s 48, 96, 144, 192 and 240. Open Label: If you experience a significant worsening of your liver function and have not permanently discontinued study drugs prior to completing the 240 Visit of the Randomized Study Treatment Phase, you may rollover into an Open-Label (OL) Phase of the study. Open-label means you and your study doctor will know what study drug you will be taking. The worsening of liver function will require confirmation by a Hepatic Events Adjudication Committee. If you undergo liver transplantation, you are not eligible to participate in the OL Phase of the study and should discontinue from the study immediately. After confirmation by the Hepatic Events Adjudication Committee, you will no longer participate in the Randomized Study Treatment Phase and will be offered the option to receive selonsertib 18 mg in the OL Phase for total treatment duration of 240 wes including the time that you participated in the Randomized Study Treatment Phase. Rollover into the OL Phase of the study must occur within 60 days of confirmation by the Hepatic Events Adjudication Committee. If you start the OL Phase of the study, you will complete the same study procedures as during the Randomized Study Treatment Phase of the study, starting with the Day 1 visit with the exception of liver biopsy. Follow-Up: One visit to your study doctor, 4 wes after your last dose in the Study Treatment Phase. Once you have completed the Study Treatment Phase, you will return to the study site for a Follow-Up visit. During this visit you will undergo a number of safety assessments and tests. These are described in detail in the tables below and include a physical exam, measurement of your vital signs, blood collection, and urine pregnancy test (if you are a female who can have children). Your study doctor will also

6 Gilead Sciences, Inc. / Protocol Number GS-US Page 6 of 28 ask about any medications you have been taking and whether you have experienced any changes to your health. Telephone Follow-Up: You will be contacted by telephone 12 wes after your 240 visit. You will be asked whether you have experienced any changes in your health since your last visit. If you have any side effects or unusual symptoms, your study doctor may require you to return to the clinic.

7 Gilead Sciences, Inc. / Protocol Number GS-US Page 7 of 28 The table below shows what will happen each time you visit the clinic. The procedures or tests are described after the table: Study Procedures Table Screening to 48 Assessments Scree ning Clinical Assessments Written Informed Consent Determine Eligibility Review your health history Physical Examination Waist Circumference Height D a y On-study-treatment Visits W ee k e k Measure your vital signs including body weight: (blood pressure, heart rate, breathing rate, and temperature) 12-lead ECG Assess liver function Liver Biopsy (Randomized Phase only) Elastography (if available) Abdominal ultrasound to check for Hepatocellular Carcinoma (HCC) Complete quality of life questionnaires Stool Frequency Assessment a b

8 Gilead Sciences, Inc. / Protocol Number GS-US Page 8 of 28 Assessments Lifestyle Modification Counseling Review any changes in your health since last visit Review medications you are taking Get study drug Bring back unused study drug and all containers since last visit Scree ning Laboratory Assessments D a y On-study-treatment Visits W ee k e k 44 Fasting Take blood samples for routine health and main study tests (chemistry, hematology, coagulation, biomarkers, blood pregnancy test at screening for women who are able to have children) Pregnancy test for women who are able to have children Take blood sample for pharmacokine tic testing c (2 ml) Urine samples will be taken for routine and main study tests x 48

9 Gilead Sciences, Inc. / Protocol Number GS-US Page 9 of 28 On-study-treatment Visits Assessments Scree ning D a y W ee k e k Urine Drug screen (amphetamine, cocaine, methadone and opiates) HIV-1, HBV, HCV Serology Optional genetic test Approximate total amount of blood taken (tablespoons) Approximate total amount of blood taken (ml)

10 Gilead Sciences, Inc. / Protocol Number GS-US Page 10 of 28 Study Procedures Table 60 to Follow Up On-study-treatment Visits Follow Up Telephone Follow-Up Assessments (EOT) Physical Examination Waist Circumference Measure your vital signs including body weight: (blood pressure, heart rate, breathing rate, and temperature) Liver Biopsy (Randomized Phase only) Assess liver function d Elastography (if available) Abdominal ultrasound to check for Hepatocellular Carcinoma (HCC) Complete quality of life questionnaires Stool Frequency Assessment Lifestyle Modification Counseling Review any changes in your health since last visit Review medications you are taking Get study drug e Bring back unused study drug and all

11 Gilead Sciences, Inc. / Protocol Number GS-US Page 11 of 28 On-study-treatment Visits Assessments containers since last visit 60 Laboratory Assessments (EOT) 156 Subject Fasting Take blood samples for routine health and main study tests (chemistry, hematology, coagulation, biomarkers, blood pregnancy test at screening for women who are able to have children) Pregnancy test for women who are able to have children Take blood sample for pharmacokinetic testing c (2 ml) Urine samples will be taken for routine and main study test Optional genetic test Approx. total blood taken (tablespoons) Approx. total blood taken (ml) Follow Up Telephone Follow-Up a b c d e Optional measurement of liver stiffness using transient elastography (FibroScan ) may be performed at Screening Perform liver stiffness measurement by elastography, if available and if optional transient elastography (Fibroscan ) was not performed at Screening (to be completed at Day 1 before or after dosing) Sample will only be collected at 1, 4, 12, 24, and 48 during the Randomized Phase and all study visits for subjects experiencing both liver and kidney impairment during the OL Phase Not to be performed at the 144 visit Not to be performed at the 240 visit

12 Gilead Sciences, Inc. / Protocol Number GS-US Page 12 of 28 Procedure or Test ECG Liver Biopsy (Randomized Phase only) Vital Signs Elastography Magnetic Resonance Elastography (MRE) Elastography Ultrasound based elastography: - FibroScan - Acoustic Radiation Force Impulse (ARFI) - Shear-Wave Elastography (SWE)) Abdominal Ultrasound Physical Exam Description Several small, sticky pads will be placed on your chest, arms, and legs. A wire from each pad goes to a machine that makes a recording of your heart rhythm. This test takes about 5 minutes. The most common type of liver biopsy is called percutaneous liver biopsy A needle will be inserted through the skin on your right side and into your liver. A small tissue sample will be collected. This test is done with local anesthetic and takes about 10 minutes. A transjugular liver biopsy may be performed at your study doctor s discretion under certain conditions. A transjugular biopsy is when a liver biopsy is performed through a catheter that has been inserted into the neck and passed into the liver, sometimes under x-ray guidance. Includes measurement of your body temperature, heart rate, breathing rate, weight, and blood pressure You will lie on an exam table that slides into a Magnetic Resonance Imaging (MRI) unit (a large, tube-shaped magnet that is open on both ends). A paddle attachment will be wrapped around your waist and sound waves will be sent through your body while you are inside the MRI unit. You will not feel the magnetic field of the MRI machine. You may feel vibrations from the paddle attachment on your skin. This test lasts about 15 minutes. You will be asked to hold your breath at least four times during the MRE scan. Each breath hold will last about seconds. A water-based gel will be applied to the skin on your right side. A probe will be held against your skin with slight pressure. The test takes about 5-10 minutes. A water-based gel will be applied to the skin on your right side. A probe will be held against your skin with slight pressure. The test takes about 5-10 minutes. A full physical examination will be performed at screening. Height will be measured at screening only. Full physical examinations will not be

13 Gilead Sciences, Inc. / Protocol Number GS-US Page 13 of 28 Assess Liver Function Stool Frequency Assessment Lifestyle modification counseling Quality of life questionnaires performed at other study visits if there is no change in your health. Your study doctor will look at physical examination and labs to determine if there has been any change in your liver health. Your study doctor or study nurse will ask about your stool frequency in the past 3 days. You will receive counseling regarding lifestyle modifications including the maintenance of a healthy diet and participating in regular exercise. You will be asked questions to assess your health, well-being from your point of view.

14 Gilead Sciences, Inc. / Protocol Number GS-US Page 14 of 28 Lab Tests and Biologic Sample Collection Main study test Routine health test Urine drug screen HCV, HBV and HIV tests Pharmacokinetic test (PK) Pregnancy test Stored samples from liver biopsy, blood, urine and pharmacokinetic testing Genetic test- OPTIONAL Future research test- OPTIONAL Description Samples of your blood, urine, and liver tissue will be used to help answer the study questions. Samples of your blood and urine will be tested to check your health. Sample of your urine will be tested for amphetamines, cocaine, and opiates (for example, heroin, morphine) Samples of your blood will be collected to check whether or not you have HCV, HBV or HIV. Samples of your blood will be tested to see how much study drug is in your body. If you are a woman who can get pregnant, a sample of your blood will be taken during the screening visit to test for pregnancy. To take part in this study, the pregnancy test must be negative. Urine pregnancy tests will be performed at Baseline/Day 1, and every 4 wes thereafter. Starting at the 48 Visit, urine pregnancy testing kits will be provided for home testing every 4 wes between in-clinic study visits. You will be contacted every 4 wes to ask you the results of your home pregnancy tests. Samples collected for any of these tests may be stored to use for additional and/ or future testing. Your stored samples will be used for research purposes only as permitted by this consent. If you agree, extra blood samples will be collected to do genetic testing. If you do not agree, you can still take part in the main study. More information is below. If you agree, leftover blood, urine, tissue samples may be stored for future testing. If you do not agree, you can still take part in the main study. More information is below. Blood samples will be taken approximately 32 times throughout the course of the study. The blood volume for each visit varies but up to 70 ml (about 4 ½ tablespoons) of blood may be drawn at a visit. The total amount of 872 ml (about 3 ¾ cups) of blood may be drawn for the 5 years duration of the study. For comparison, a standard blood donation at a blood collection center, once in any 56-day period, is about 500 ml (approximately 2 cups of blood). If you roll over in to the Open-Label Phase of the study, the total amount of blood drawn may vary. Additional blood samples may be required if any of your blood tests are not normal. It is possible that more than one attempt to obtain a blood sample may be necessary.

15 Gilead Sciences, Inc. / Protocol Number GS-US Page 15 of 28 Study Drug Get study drug Take study drug Bring back study drug and containers Description At the visits marked on the table, you will be given study drugs to take home with you. You will receive your first dose of study drugs at your Baseline/Day 1 visit. Study drugs should be stored at room temperature between 15 C and 30 C (59 F and 86 F). Take your study drug tablets (one from each type of bottle) by mouth once daily at approximately the same time each day. The tablets should be swallowed whole with water and can be taken with or without food. If you miss a dose, you should take your next dose at the regular dosing time. Bring back all unused study drug and all study drug containers (even if they are empty or used). Your study doctor or study nurse will count how many doses you have taken. Your study doctor or study nurse will ask about any doses you did not take or if you took any extra doses. WHAT RESTRICTIONS ARE THERE DURING THIS STUDY? Fasting (no food or liquids except water) is required for tests at all study visits. You may not eat or drink (except water) for approximately 8 hours prior to each of those visits. There are certain medications that you cannot take during this study. Your study doctor will go over these with you during your screening visit. WHAT SAMPLES WILL BE STORED? WHAT TESTS WILL BE DONE ON THESE SAMPLES? Some of your blood, urine, and liver biopsy samples drawn during the study will be stored. Your stored samples and the information collected about you during the study may be used by the Study Sponsor or its research partners to help answer study questions about the study drug or your illness. At the end of this study, leftover samples may be held in storage by Gilead Sciences, Inc. for up to 15 years. Your samples will be assigned a unique identifying code, but not your name or other individually identifiable information. You may request that your stored samples be destroyed at any time by writing to the study doctor at the address listed in this form. Your stored samples will be used for research purposes only as permitted by this consent. No human genetic testing will be done without your separate written consent.

16 Gilead Sciences, Inc. / Protocol Number GS-US Page 16 of 28 WHAT ARE THE POSSIBLE RISKS OF BEING IN THIS STUDY? Selonsertib COMMON ADVERSE EVENTS Selonsertib (SEL, formerly GS-4997) has been studied in 13 Phase 1 and 2 clinical studies involving approximately 800 subjects including patients and healthy volunteers. In 3 Phase 2 studies of 423 SEL treated subjects (62 with non-alcoholic steatohepatitis [NASH], 113 with pulmonary artery hypertension [PAH], and 248 with diabetic kidney disease [DKD]), most side effects reported were mild. The most common side effects occurring in greater than 10% of SEL treated subjects in any of the 3 Phase 2 studies were: Headache Diarrhea Nausea Sinusitis (inflammation of the sinuses) Nasopharyngitis and upper respiratory tract infection (common cold) Cough Dizziness Fatigue (feeling tired) Abnormal liver tests have been observed with SEL. If this happens to you, your study doctor may request additional tests. In animal studies, SEL has been associated with embryofetal toxicity (malformations in fetuses and spontaneous abortions). Please talk to your study doctor for more details about risks or adverse events related to Selonsertib. LIVER BIOPSY RISKS A percutaneous liver biopsy is a common test used to confirm the diagnosis for hepatitis. Many doctors also do a liver biopsy to help confirm how serious the liver is damaged. Risks and complications of liver biopsy may include: Pain and discomfort located at or near the puncture site and radiating upwards toward the right shoulder region Bleeding at the biopsy site Possible internal bleeding after the procedure Infections at the biopsy site or internal organs Puncture of internal organs (gall bladder, lung, intestine or kidney) Allergic reaction to the anesthetic 1 in 10,000 risk of death from a complication resulting from a liver biopsy Additional risks of a transjugular liver biopsy may include: Blood may pool around the site where the catheter was inserted, potentially causing pain and swelling

17 Gilead Sciences, Inc. / Protocol Number GS-US Page 17 of 28 Rarely, the transjugular procedure can injure nerves and affect the face and eyes, causing short-term problems, such as a drooping eyelid You may be hoarse, have a weak voice or lose your voice for a short time If the needle accidentally sticks your lung, the result may be a collapsed lung (pneumothorax) If the procedure is performed under x-ray, there may be risks associated with the radiation exposure including an increased risk of cancer later in life The risks and complications of liver biopsy mentioned above is by no means a complete list. Your study doctor will discuss all the risks and complications of the biopsy with you. You may be asked to read, understand and sign a separate consent for a liver biopsy by your study doctor. LIVER STIFFNESS MEASUREMENT BY ELASTOGRAPHY RISKS: MAGNETIC RESONANCE ELASTOGRAPHY (MRE) Magnetic resonance elastography (MRE) imaging uses a strong magnetic field, which is not harmful in itself, but implanted medical devices that contain metal may malfunction or cause problems during an MRE exam. If you have any implanted devices please inform the study doctors before the procedure. Some people may feel claustrophobic during this procedure. Please let the study team know if you have experienced claustrophobia before. ULTRASOUND BASED ELASTOGRAPHY (FIBROSCAN, ARFI, AND SWE) There are no known risks for these procedures. ABDOMINAL ULTRASOUND There are no known risks for this procedure. ECG After you have an ECG, you may have mild irritation, slight redness, and itching on your skin where the recording patches are attached. You may have your chest shaved for this procedure. BLOOD DRAWS Collecting a blood sample from a vein may cause pain, bruising, lightheadedness, fainting, and very rarely, infection at the site of the needle stick. QUESTIONNAIRES Some of the questions may seem personal and may make you feel uncomfortable. If you have any questions or concerns while answering these questions, please talk to your study doctor.

18 Gilead Sciences, Inc. / Protocol Number GS-US Page 18 of 28 FASTING Fasting could cause dizziness, headache, stomach discomfort, or fainting. ALLERGIC REACTION Allergic reaction is always possible with a drug you have not taken. Serious allergic reactions that can be life-threatening may occur. Some things that happen during any allergic reaction to any type of medication are: rash having a hard time breathing wheezing when you breathe sudden drop in blood pressure swelling around the mouth, throat, or eyes fast pulse sweating If any of these symptoms happen to you while you are in the study you should se medical help right away and be sure to tell the study doctor as soon as you can. PRIVACY RISKS If your genetic research data are shared with unauthorized users, you may be at risk of loss of the privacy of your health data. This risk is minimized by protections described in the WHO WILL HAVE ACCESS TO YOUR MEDICAL RECORDS? section below. UNKNOWN/UNEPECTED RISKS AND DISCOMFORTS There are adverse events (side effects) that are not known or happen rarely when subjects take these study drugs. You will be told of any new information that might cause you to change your mind about continuing to take part in this study. As with any new drug, extra care has to be taken to monitor the side effects that are not always obvious. If you feel any side effects or unusual symptoms, please notify your study doctor as soon as possible at the phone number listed in this form PREGNANCY AND BREAST-FEEDING While the effects of selonsertib on an unborn baby or a nursing infant are not known, selonsertib treatment caused malformations (birth defects) in the fetuses (unborn babies) of pregnant rats and rabbits. These birth defects happened at doses of selonsertib 3 times higher than those given in this study. Based on this animal data, selonsertib may cause birth defects in humans. Do not participate in this study unless you understand and accept this risk and are willing to take appropriate measures to avoid pregnancy. For this reason, pregnant women,

19 Gilead Sciences, Inc. / Protocol Number GS-US Page 19 of 28 women who wish to become pregnant, and breast-feeding women will not be enrolled in this study. If you are breast-feeding, you must stop nursing before your first dose of study drug(s). You must refrain from egg donation or harvest for the duration of the study and for 30 days after the last dose of study drug(s). It is very important to prevent pregnancy from screening to study completion and for 30 days after stopping the study drug(s). You must either completely avoid sexual intercourse with a person of the opposite sex, or MUST choose from the methods of birth control listed below. CONTRACEPTION REQUIREMENTS FOR FEMALE SUBJECTS OF CHILDBEARING POTENTIAL If you are a female of childbearing age, you must have a negative serum pregnancy test at screening and a negative pregnancy test on the Day 1 visit prior to randomization. Pregnancy tests will be performed at monthly intervals thereafter. You must agree to one of the following from Screening until 30 days following the last dose of study drug. Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable method of contraception only when it is in line with the subject s preferred and usual lifestyle. Consistent and correct use of one of the following methods of birth control listed below: 1) Intrauterine device (IUD) with a failure rate of less than 1% per year 2) Tubal sterilization 3) Essure micro-insert system (provided confirmation of success 3 months after procedure) 4) Vasectomy in the male partner (provided that the partner is the sole sexual partner and had confirmation of surgical success 3 months after procedure) The above described methods are considered preferred methods of highly effective contraception in this protocol. Should you wish to use a hormonally based method, use of a male condom by your male partner is required. If you utilize a hormonal contraceptive as one of your birth control methods, you must have used the same method for at least three months prior to receiving your first study drug. Hormonallybased contraceptives permitted for use in this study are as follows: Hormonal methods (each method must be used with a condom in the male partner): 1) Oral contraceptives (either combined or progesterone only) 2) Injectable progesterone 3) Implants of levonorgestrel 4) Transdermal contraceptive patch 5) Contraceptive vaginal ring

20 Gilead Sciences, Inc. / Protocol Number GS-US Page 20 of 28 CONTRACEPTION REQUIREMENTS FOR MALE SUBJECT Male subjects with female partners of childbearing potential must use condoms during treatment until 30 days after the last dose of study drug. Female partners of male study subjects are asked to select one of the above methods. WHAT ARE THE POSSIBLE BENEFITS OF THIS STUDY? You may not receive any benefit from taking part in this study. Studies are a way for doctors to see if a drug is useful in fighting a disease. Your taking part in this study may help scientists, doctors and people with fibrosis of the liver understand more about the treatment of your disease. By taking part in this study, your health will be monitored closely at study visits. WHAT ARE YOUR TREATMENT OPTIONS? ight loss with diet and exercise is the only therapeutic strategy that has been shown to be helpful in NASH; however, weight loss has never been shown to reverse cirrhosis in NASH patients. There are no medicines available today that are specifically designed to treat NASH and none for liver fibrosis (scarring) or cirrhosis. Your study doctor will discuss appropriate treatment options and the risks and benefits with you. You can discuss if you want to have any treatment or if you want to choose another treatment such as other investigational drugs or medications that can treat the symptoms of your disease. These treatments include those that are already approved and sold. You will be made aware of any new findings that become available during the course of the study that may affect your willingness to take part. WHAT HAPPENS IF YOU DO NOT WANT TO TAKE PART IN THIS STUDY? WHAT HAPPENS IF YOU NO LONGER WANT TO TAKE PART IN THE STUDY? Your decision to take part in this study is voluntary. You can refuse to take part or stop taking part at any time without giving a reason. If you decide to stop the study at any time, your exit from this study will not affect the medical care which you otherwise may receive. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Your participation in this study may be stopped at any time by your study doctor, Gilead Sciences, Inc., or regulatory authorities. If you discontinue study treatment early, you are encouraged to complete all the study visits through 240, the Follow-Up Visit which should occur 4 wes after the 240 visit and Telephone Follow-Up Visit 12 wes after your 240 visit. This is to ensure your safety as well as to collect important information.

21 Gilead Sciences, Inc. / Protocol Number GS-US Page 21 of 28 If you decide to leave the study, you are strongly urged to return to the study doctor for the 240 visit, Follow-Up Visit which should occur 4 wes after last dose and Telephone Follow-Up Visit 12 wes after your 240 visit. This is to ensure your safety as well as to collect important information. Your taking part in this study may be stopped at any time by a) your study doctor, b) Gilead Sciences, Inc., c) the FDA, d) Chesapeake IRB (Institutional Review Board - a review group that gives approval to your study doctor to conduct this study), and other appropriate regulatory agencies. Your study doctor may decide for your medical safety to stop your study drug(s) or take you off the study. You may be taken off the study if your study doctor learns you did not give a correct medical history or did not follow instructions for the study. If you are taken off the study, you will no longer receive the study drug(s). If your study drug(s) is stopped, your study doctor will closely monitor your overall health. If you stop participating in this study, information about whether you are alive or deceased may be collected. This information may also be gathered from public records such as government census or death records. HOW MUCH WILL STUDY TREATMENT COST YOU? The study drug used in this study will be given to you at no charge. All study visits and fees for lab tests and procedures that are part of this study will be provided at no cost to you. You or your usual health care payer will be responsible for any other health care costs. WILL YOU BE PAID TO BE PART OF THIS STUDY? You will not be paid for participating in this study. WHAT HAPPENS IF YOU ARE INJURED? If you become sick or injured as a direct result of taking the study drug and/or following the study procedures, the study site will provide you with medical treatment. The Sponsor, Gilead Sciences, Inc., will reimburse you or the study site for the reasonable and necessary costs of such medical treatment, provided that you have followed the instructions of the Study Doctor. No other form of reimbursement for study-related injury or illness is offered by the Sponsor. You should immediately contact your Study Doctor at the contact information shown on the first page of this form in the event you experience any study-related illness or injury. If you receive Medicare benefits, the Sponsor, Gilead Sciences, Inc., is required by law to report payments made to you for treatment, complications, and injuries that arise from this Study. Information that you are taking part in the Study, medical treatments received, Medicare claims, and other personal information about you such as your

22 Gilead Sciences, Inc. / Protocol Number GS-US Page 22 of 28 name, social security number, and date of birth, will be provided to the Centers of Medicare and Medicaid Services and its agents and/or contractors for this purpose. You do not give up any legal rights by signing this form. You are not precluded from seing to collect compensation for injury related to malpractice, fault, or blame on the part of those involved in the research. GETTING ANSWERS TO YOUR QUESTIONS OR CONCERNS ABOUT THE STUDY You can ask questions about this consent form or the study (before you decide to start the study, at any time during the study, or after completion of the study). Questions may include: Who to contact in the case of a research-related injury or illness; Payment or compensation for being in the study, if any; Your responsibilities as a study subject; Eligibility to participate in the research; The study doctor s or study site s decision to exclude you from participation; Results of tests and/or procedures; Other questions, concerns, or complaints. Contact the study doctor or study staff listed on the first page of this form with any questions, concerns or complaints. GETTING ANSWERS TO YOUR QUESTIONS ABOUT YOUR RIGHTS AS A RESEARCH SUBJECT This study has been reviewed by an Institutional Review Board (IRB). This Committee reviewed this study to help ensure that your rights and welfare are protected and that this study is carried out in an ethical manner. For questions about your rights as a research subject, contact: By mail: Study Subject Adviser Chesapeake IRB 6940 Columbia Gateway Drive, Suite 110 Columbia, MD or call toll free: or by adviser@chesapeakeirb.com Please reference the following number when contacting the Study Subject Adviser: Pro

23 Gilead Sciences, Inc. / Protocol Number GS-US Page 23 of 28 WHO WILL HAVE ACCESS TO YOUR MEDICAL RECORDS? Records identifying you will be kept confidential and, to the extent permitted by applicable laws and/or regulations, will not be made publicly available. In the event of any publication regarding this study, your identity will remain confidential. Representatives from government agencies, including the U.S. Food and Drug Administration ( FDA ), the institutional review board (IRB), the Sponsor and/or the Sponsor s authorized representatives may need access to your original medical records and study records for the purpose of checking data collected for the study. By signing this consent form, you authorize this access. Your coded study information may also be used for additional unanticipated medical and/or scientific research projects in the future relating to your disease or similar diseases and development of the study drug (but at all times in compliance with applicable law and regulation). By signing this consent form you agree that you will not be able to have access to your personal health information related to this study until the study is over. This is done to maintain the scientific integrity of the study. After the study is complete, you can obtain access to your information through your Study Doctor. A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for health insurance companies, group health plans and most employers to discriminate against you based on your genetic information. This law generally will protect you in the following ways: Health insurance companies and group health plans may not request your genetic information that the sponsor will get from this research. Health insurance companies and group health plans may not use your genetic information when making decisions regarding your eligibility or premiums. Employers with 15 or more employees may not use your genetic information that the sponsor will get from this research when making a decision to hire, promote, or fire you or when setting the terms of your employment. All health insurance companies and group health plans and all employers with 15 or more people must follow this law. Be aware that this Federal law does not protect you against genetic discrimination by companies that sell life insurance, disability insurance or long-term care insurance. Authorization to Use and Disclose Records During this study your Study Doctor, nurses and other study personnel will record information about you, your health and your participation in the study on forms provided by Sponsor. These forms are known as case report forms. You will not be able to participate in this study if you do not consent to the collection of this information about you.

24 Gilead Sciences, Inc. / Protocol Number GS-US Page 24 of 28 The information collected about you, will be held by the study site, Sponsor and Sponsor s authorized representatives. To ensure that your personal information is kept confidential, your name and any other information that allows you to be identified directly will not be entered on the case report forms or included in any records or samples your study doctor provides to Sponsor or Sponsor s authorized representatives. Instead, you will only be identified by a code. The code is used so that your study doctor can identify you if necessary. The Sponsor and its authorized representatives will analyze and use the coded information they receive for the purposes of this study. Such purposes include: checking your suitability to take part in the study, monitoring your treatment with the study drug, comparing and pooling your study treatment results with those of other subjects in clinical studies, establishing whether the study drug meets the appropriate standards of safety set by the authorities, establishing whether the study drug is effective, supporting the development of the study drug, supporting the licensing application for regulatory approval of the study drug anywhere in the world, supporting the marketing, distribution, sale and use of the study drug anywhere in the world, and/or as otherwise required or authorized by law. Your coded study information may also be used for additional unanticipated medical and/or scientific research projects in the future relating to your disease or similar diseases and development of the study drug (but at all times in compliance with applicable law and regulation). If necessary for these purposes, the Sponsor may share your information with its affiliates, people and companies with whom the Sponsor works, and regulatory or other governmental agencies, such as the FDA. Although efforts will be made to protect your privacy, absolute confidentiality of your records cannot be guaranteed. Your medical information and records may be re-disclosed and no longer protected by federal privacy law. As explained in this consent form, your participation in this study is voluntary and you may withdraw from the study at any time by informing your Study Doctor. By signing this consent, you authorize the collection and use of information about you as described in this consent. You may revoke (take back) this authorization for the collection and use of information about you by informing your Study Doctor in writing at the address listed on the first page of this form. If you withdraw from the study or if you revoke your authorization for the collection and use of information about you, your participation in the study will end and the study personnel will stop collecting information from you. The Sponsor will need to keep and use any research results that have already been collected. The Sponsor must do this to comply with its legal obligations and to maintain

25 Gilead Sciences, Inc. / Protocol Number GS-US Page 25 of 28 the scientific integrity of the study. Your decision to withdraw from the study or to revoke your authorization for the collection and use of information about you will not result in any penalty or loss of access to treatment or other benefits to which you are entitled. This authorization has no expiration date, unless and until you revoke it. In California and any other state that requires an expiration date, this authorization will expire 50 years after you sign this authorization document. If you have any questions about the collection and use of information about you, you should ask your Study Doctor. WHERE CAN YOU FIND MORE INFORMATION ABOUT THIS STUDY? A description of this clinical trial will be available on as required by U.S. Law. This b site will not include information that can identify you. At most, the b site will include a summary of the results. You can search this b site at any time.

26 Gilead Sciences, Inc. / Protocol Number GS-US Page 26 of 28 AGREEMENT TO BE IN THE STUDY By signing this informed consent form, I acknowledge that: (1) I have carefully read and understand the information in this form. (2) The purpose and procedures of this research study have been fully explained to me. I was able to ask questions and all of my questions were answered to my satisfaction. (3) I have been informed of the study drugs and procedures of the study that are being tested. I have been informed of possible risks as a result of taking part in this study that could happen from both known and unknown causes. (4) I understand that I am free to withdraw my consent and to stop my participation in this study at any time. The possible effect on my health, if any, of stopping the study early has been explained to me. (5) I understand that stopping the study will not impact my medical care and treatment options. Subject Subject Printed Name Signature Date Person Obtaining Consent Printed Name & Title Signature Date Witness (if applicable) Witness Printed Name Signature Date

27 Gilead Sciences, Inc. / Protocol Number GS-US Page 27 of 28 Optional Future Research Consent You are being asked to take part in future research, including genomic (genetic) research. If you decide to not take part in this optional future research, you can still take part in the main study. This research may help scientists to better understand: How your disease and related diseases work The effect of the study drug and/or other medications on the body How the study drug is processed by the body Who could benefit from the study drug Why some people have adverse events The results of the tests done on your blood, urine, and tissue samples (also called biologic sample(s)) will not be given to you or your study doctor. Information from these tests may be printed in a medical journal or presented at scientific meetings. Only a summary of data from all subjects will be used. The results of this research may lead to an approved product for the treatment, prevention or confirmation of disease. You understand and agree that by consenting to the storage and testing of your samples for possible future research, you authorize the use of your sample, the by-products of the sample, and any products developed from the sample as described by this form. The Study Sponsor, other researchers, or companies may patent or sell discoveries that result from this research. You will not be paid any money if this happens. Genomic research is the study of your genes (factors inherited from our parents) and how they work. All genomic research will be done collectively and the Study Sponsor will take every step to protect your identity by giving your sample a code. Results of your genomic testing will NOT be made available to you or your study doctor. This is done to decrease the risk of accidental disclosure of genetic research data. This means that these results will not be made available to you, your family members, your private doctor, your employer, your insurance company or any other party unless required by law. You may choose to take part in none, some, or all of the optional future research, listed below. If you decide you no longer want to take part in this future testing of your biologic sample(s), your unused sample(s) will be destroyed. The Study Sponsor may continue to use and disclose the results from samples that were tested before you withdrew your consent. If you decide to no longer take part in the main study or are taken off the main study by your study doctor, the biologic samples you provided for future research will still be kept and may be used for future testing. If you decide you no longer want to take part in this