WHAT DOES MY PARTICIPATION INVOLVE?

Transcription

1 PARTICIPANT INFORMATION SHEET AND CONSENT FORM Sponsor: Local Sponsor: Protocol No: Protocol Title: Investigator: Location: Teva Branded Pharmaceutical Products R&D, Inc. Pharmaceutical Research Associates Pty Ltd A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo Controlled, Parallel Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV versus Placebo for the Prevention of Episodic Cluster Headache Dr Nicole Limberg Wesley Medical Research PART 1 1. INTRODUCTION WHAT DOES MY PARTICIPATION INVOLVE? You are being invited to participate in a research study. This is because you have been diagnosed with Episodic Cluster Headaches (ECH). The research study is testing a new treatment for ECH. The new treatment is called TEV ("investigational drug"). This Participant Information Sheet/Consent Form tells you about the research study. It explains the tests and treatments involved. Knowing what is involved will help you decide if you want to take part in the research study. Please read this information carefully. Ask questions about anything that you don t understand or want to know more about. Before deciding whether or not to take part, you might want to talk about it with a relative, friend, or your local doctor. Participation in this research study is voluntary. If you don t wish to take part, you don t have to. You will receive the best possible care whether or not you take part. If you decide you want to take part in the research study, you will be asked to sign the consent section. By signing it you are telling us that you: Understand what you have read Consent to take part in the research study Consent to have the tests and treatments that are described Consent to the use of your personal and health information as described. You will be given a copy of this Participant Information and Consent Form to keep. Page 1 of 22

2 2. WHAT IS THE PURPOSE OF THIS RESEARCH STUDY? The purpose of this research study is to evaluate how effective and how safe TEV is for the prevention of ECH. Also 2 routes of administration will be compared: intravenous infusion (to drip into the blood vessel through a plastic tube) and subcutaneous injection (under the skin). This will be done by evaluating the number of cluster headache (CH) attacks during 12 weeks of treatment with TEV TEV is an investigational drug. Investigational means that the drug has not been approved by the Australian Government s Therapeutic Goods Administration (TGA). As part of this study, you may be given a placebo. Human studies have shown that TEV is effective in preventive treatment of migraine and it may be also useful for the preventive treatment of episodic cluster headache. This study is being conducted by a pharmaceutical company, Teva Branded Pharmaceutical Products R&D, Inc. (Teva, the Sponsor ) and sponsored in Australia by Pharmaceutical Research Associates Pty Ltd. ( PRA ). Approximately 300 participants (men or women 18 to 70 years of age inclusive) will take part in this research study. 3. WHAT DOES PARTICIPATION IN THIS RESEARCH INVOLVE? To participate in this study you can be male or female and you must be between 18 and 70 years of age, and diagnosed with ECH. If you are suitable and decide to participate in the study, then you will be one of approximately 300 participants. Sometimes it is not known which way of treating patients is best. To find out, researchers need to compare different treatments. People are put into groups and each group given a different treatment. The results are compared to see if one is better. In this study, TEV (administered intravenously and subcutaneously) will be compared with a placebo. A placebo is a medication which looks exactly like the investigational drug, but has no active ingredient. If you participate in this study, you have an equal 1 in 3 chance of receiving one of the following treatments; Group 1: - Visit 2: 1 hour of intravenous infusion of TEV mg followed by 3 subcutaneous injections of placebo - Visits 3 and 4: 1 subcutaneous injection of TEV mg Group 2: - Visit 2: 1 hour of intravenous infusion of placebo followed by 3 subcutaneous injections of TEV mg (You will receive 675 mg of TEV in total) - Visits 3 and 4: 1 subcutaneous injection of placebo Group 3: - Visit 2: 1 hour of intravenous infusion of placebo followed by 3 subcutaneous injections of placebo Page 2 of 22

3 - Visits 3 and 4: 1 subcutaneous injection of placebo To try to make sure the groups are the same to start with, each participant is put into a group randomly (by chance, like in flipping a coin). This study is called a double blind trial. It means that you and your study doctor will not know what study drug you will be taking (although, if your study doctor needs to find out he/she will be able to do so). Your participation in the study will last for a total of 13 weeks. This study requires 5 visits to the clinic over a period of 13 weeks. Study Visits will be conducted approximately every 4 weeks. The duration of treatment is 12 weeks. Overview of Study Procedures: Screening visit (Visit 1) and Run-In period: The purpose of this visit is for the study doctor to assess whether you meet all requirements for this study, which were defined as a standard for all study participants. The following procedures/assessments will be performed: The study doctor or study staff will ask you to give personal information such as your initials, date of birth and racial or ethnic origin. The study doctor will review your medical history, your prior medication history and psychiatric history (Up to 2 preventive medications are allowed to enter the study) You will undergo a complete physical examination, including weight and height measurements. Your vital signs will be measured: blood pressure, heart rate, and temperature. You will have an Electrocardiogram (ECG) - which measures the electrical activity of your heart. The study staff will take bloods by inserting a needle usually into a vein in your arm. The blood samples are collected: - To perform routine safety laboratory tests (including haematology and chemistry) - To test the presence for Hepatitis B and C virus (if required) You will receive electronic diary device. Research staff will explain how to use it to record information about your headaches. You should complete this diary daily; this day or in the following two days at home as instructed by your study doctor. This diary will be reviewed at visits 2, 3, 4 and 5 and between visits by study staff. You will answer two questionnaires which will be recorded in the electronic diary device at home. If you are a female of childbearing potential, you will have a blood pregnancy test performed. You cannot participate in this study if you are pregnant. If you are a postmenopausal female for example, you have not had your period for 12 months or more without interventions such as an IUD or other medications to prevent your period, you will have blood drawn for FSH (Follicle Stimulating Hormone) test to confirm menopause. Page 3 of 22

4 Visits 2, 3 and 4 You will be asked to return to the site at visit 2 to confirm if you are still suitable to take part in the study. If you are found suitable, the following procedures/assessments will be performed: You will undergo a complete physical examination, including weight The study staff will measure your vital signs including blood pressure, heart rate, and temperature Blood will be collected: - To perform routine safety laboratory tests (including haematology and chemistry) - To perform tests to measure blood concentrations of TEV (pharmacokinetic analysis) - To perform an Anti-Drug Antibody evaluation (ADA assay) (evaluation of amount of antibodies - proteins produced by immune cells that your body develops against the drug). This will be collected at visits 2, 3 and 4. Bloods and a urine sample will be taken for biomarker analysis. Biomarkers are any biological markers (like Deoxyribonucleic acid [DNA], ribonucleic acid [RNA] and proteins) that are associated with a disease, a treatment, or an outcome. This testing will help researchers understand the disease, and assess drug activity in your body, and response of your body to the drug. If you are a female of childbearing potential, a urine pregnancy test will be done at visits 2, 3 and 4 You will have an ECG at visit 2 only. You will receive study medication in the clinic. Local injection site will be assessed as well as evaluation of allergic reactions. The study staff will review your electronic diary. You will answer several questionnaires about your headaches and how you feel which will be entered into the investigational Site tablet Visit 5 (End-of-Treatment Visit (EOT) / Early Withdrawal) This visit will be done once you have completed the previous visits or if you leave the study early. The same procedures as those performed at visits 2, 3 and 4 will be performed at this visit as well. The only differences are: Local injection site will not be assessed. You will return electronic diary device You won t receive study medication. Blood pregnancy test will be performed ECG will be performed The blood tests will require approximately ml or a bit more than ½ cup in total of your blood to be collected during the entire study. An additional blood (30 ml) sample might be collected to ensure your liver works correctly. Table of study procedures The table below shows details of what will happen each time you visit the clinic. Page 4 of 22

5 Study period Pretreatment period (including screening visit and run-in period) Double-blind treatment period Visit number V1 V2 V3 V4 V5 Week number Week -1 Week 0 Week 4 Week 8 Week 12 Procedures and assessments (completed before dosing, when applicable, unless otherwise noted) Screening Baseline dose 1 day 0 (+3 days) Visit 3 day 28 (±3 days) Visit 4 day 56 (±3 days) EOT or early withdrawal day 84 (±3 days) Informed consent Medical and psychiatric history Prior medication history Record demographic characteristics Physical examination, including weight and height Electrocardiogram Vital signs measurement Adverse events Other medication inquiry Clinical laboratory tests Pregnancy test in blood ( female of childbearing potential only) Page 5 of 22

6 Study period Pretreatment period (including screening visit and run-in period) Double-blind treatment period Visit number V1 V2 V3 V4 V5 Week number Week -1 Week 0 Week 4 Week 8 Week 12 Procedures and assessments (completed before dosing, when applicable, unless otherwise noted) Screening Baseline dose 1 day 0 (+3 days) Visit 3 day 28 (±3 days) Visit 4 day 56 (±3 days) EOT or early withdrawal day 84 (±3 days) Pregnancy test in urine ( female of childbearing potential only) Provide electronic diary device Enter cluster headache attack information and scale in the electronic diary device Review electronic diary data Return electronic diary device Blood samples ( 4 ml) for pharmacokinetics analysis Blood samples (5 ml) for Antidrug- Antibody analysis Optional Blood sample (6 ml) for pharmacogenomic analysis Page 6 of 22

7 Study period Pretreatment period (including screening visit and run-in period) Double-blind treatment period Visit number V1 V2 V3 V4 V5 Week number Week -1 Week 0 Week 4 Week 8 Week 12 Procedures and assessments (completed before dosing, when applicable, unless otherwise noted) Screening Baseline dose 1 day 0 (+3 days) Visit 3 day 28 (±3 days) Visit 4 day 56 (±3 days) EOT or early withdrawal day 84 (±3 days) Blood collection for serum, plasma, and RNA biomarker analysis (17 ml) Urine collection for biomarker analysis (5 ml) Complete questionnaires. (Depending on the visit you will be asked to complete different questionnaires about your health and wellbeing, how your disease affects your work and daily activities, the severity of your illness and the intensity of pain. In all visits you will answer a questionnaire to evaluate your psychological well-being). (Only 1 questionnaire to evaluate in case you have suicidal ideation) Page 7 of 22

8 Study period Pretreatment period (including screening visit and run-in period) Double-blind treatment period Visit number V1 V2 V3 V4 V5 Week number Week -1 Week 0 Week 4 Week 8 Week 12 Procedures and assessments (completed before dosing, when applicable, unless otherwise noted) Screening Baseline dose 1 day 0 (+3 days) Visit 3 day 28 (±3 days) Visit 4 day 56 (±3 days) EOT or early withdrawal day 84 (±3 days) Impact on Partner and Family questionnaire. ( If applicable to be completed by partners/family members) Receive study drug Hypersensitivity/anaphylaxis reaction assessment Injection site assessments Page 8 of 22

9 4. WHAT ARE MY RESPONSIBILITIES? As a participant in this study, you have certain responsibilities to help ensure your safety. These responsibilities are listed below. You must: Follow study doctor s instructions; Complete all required visits to the study clinic; you should remain in the clinic for safety observation for at least 60 minutes after you receive study drug; Report your medication history and prior and concomitant medication (concomitant means any medication that you are currently taking which may include herbal remedies, vitamins and any over-the-counter medications) if you start to take new medicines. The study doctor will let you know which medicines you aren t allowed to take during your participation in this clinical trial. Report all side effects and medical problems to your study doctor or staff; Report immediately if you (or your partner, if you are a man) become pregnant; Complete electronic diaries daily; this day or in the following two days, at home and in the clinic; Inform the study doctor or the study staff if you decide you no longer wish to participate in the study. For your own safety we recommend you to attend a close out visit. You must not donate blood during the study for approximately 7.5 months after the study. 5. OTHER RELEVANT INFORMATION ABOUT THE RESEARCH STUDY a) Cost: You will not have any additional costs if you participate in this study. You will receive the study drug used for this study free of charge and there will be no charges for the visits, tests or procedures that are part of this study. All costs not related to the study, including those related to the normal treatment of your disease, will be your responsibility. b) Payments: You will not be paid for your participation in the study, but you will be reimbursed for any reasonable expenses incurred by taking part, for example travel to and from the study site for your visits and/or parking at the hospital. Furthermore if you complete all questions asked in the electronic headache diary between study visits, you will receive $26 for visits 2-5. If you miss more than 1 day per week of diary entries, you will not receive the additional payment for that study visit. The study doctor or study staff can tell you more about when you will get reimbursed. 6. DO I HAVE TO TAKE PART IN THIS RESEARCH STUDY? Your participation in this research study is voluntary. If you do not wish to take part, you do not have to. If you decide to take part and later change your mind, you are free to withdraw from the study at any stage. If you do decide to take part, you will be given this Participant Information Sheet and Consent Form to sign and you will be given a copy to keep. Your decision whether or not to take part, or to take part and then withdraw, will not have an adverse impact on your present or future health care, your relationship with those treating you or your relationship with Wesley Medical Research. You should be aware that data collected by Page 9 of 22

10 the sponsor up to the time you withdraw will form part of the research study results. If you do not want them to do this, you should not participate in the study To ensure your safety, you will be asked to undergo a final evaluation visit. If you wish to withdraw from the study, you should contact the study doctor. Your partner/family member will also be asked to be part of this study by completing an Impact on Partner and Family questionnaire at different time points. This is optional, if they agree then they will be asked to sign a separate Informed Consent Form. If your partner/family member agrees to take part then they will be asked to attend the following study visits with you; Visit 2 (week 0), Visit 3 (week 4) and Visit 5 (week 12) or 3 days after or 3 days before if they are unable to appear at the same time. 7. WHAT ARE THE ALTERNATIVES TO PARTICIPATION? If you do not wish to participate in this study, you will continue to be treated by your normal doctor and your care will not be affected in any way. There are currently no other alternative treatments available for the prevention of episodic headache, however your doctor may be able to provide treatment to help with some of your symptoms. These treatments should be discussed with your doctor. 8. WHAT ARE THE POSSIBLE BENEFITS OF TAKING PART? We cannot promise that participating in the study will help you. The study drug may result in an improvement in the prevention of your of episodic cluster headache or you may have no improvement at all. It is possible that you may feel worse. The information we get from this study may help improve the prevention episodic cluster headache. 9. WHAT ARE THE POSSIBLE RISKS AND DISADVANTAGES OF TAKING PART? Medical treatments often cause side effects. You may have none, some or all of the effects listed below, and they may be mild, moderate or severe. If you have any of these side effects, or are worried about them, talk with your study doctor. Your study doctor will also be looking out for side effects. There may be side effects that the researchers do not expect or do not know about and that may be serious. Tell your study doctor immediately about any new or unusual symptoms that you get. Many side effects go away shortly after treatment ends. However, sometimes side effects can be serious, long lasting or permanent. If a severe side effect or reaction occurs, your study doctor may need to stop your treatment. Your study doctor will discuss the best way of managing any side effects with you. Page 10 of 22

11 Your family and or caregivers will be instructed to monitor you in case you have any unusual changes in your behaviour as well as any suicidal thoughts or behaviour. They will be instructed to report these symptoms to your study doctor immediately. The possible discomforts, side effects and risks related to TEV treatment are not all known yet. The study drug is generally well tolerated. A total of 484 participants/patients (118 healthy participants and 366 patients with migraine) have been treated with at least 1 dose of TEV in the past in clinical trials. Also there are 5 other ongoing trials with the study drug for migraines. This section describes the most frequent side effects which occurred in participants who were treated with TEV : Overall side effects of TEV-48125: Injection site disorders/reactions in some of the patients that received TEV as subcutaneous injections: Injection site erythema (redness of the skin that is often a sign of infection or inflammation) Injection site pain Injection site pruritus (itchiness). injection site dermatitis (inflammation of the skin) drug hypersensitivity (was observed in one patient treated with intravenous administration (infusion related reaction) and one patient with subcutaneous injection of TEV-48125) -Infusion-related reaction for the patients for patients treated with intravenous TEV-48125: administration site pain infusion-related reaction Other reported side effects were headache, back pain, and upper respiratory tract infection. Potential risks for taking study drug include inflammation of your blood vessels, development of antidrug antibodies (ADAs), raised liver enzymes, and cardiovascular effects (e.g. on blood pressure, heart rates, other). Drug interactions: Taking certain other medicines together with TEV may increase the chance of unwanted effects. The risk will depend on how much of each medicine you take every day, and on how long you take the medicines together. Like in the case of infusion of any drug of this type, there is the infusion associated risks of fever, headache, nausea, vomiting or hypotension (low blood pressure). If your study doctor instructs you to take these medicines together on a regular basis, follow his or her directions carefully. Page 11 of 22

12 Unknown side effects: There may be risks or side effects related to the study drug or other study procedures that are unknown at this time. Let your study doctor know if you experience any side effects, even those which are not mentioned in this Information Sheet. Risks of Procedures Conducted During the Study: Blood Tests Risks: Blood samples will be collected during this study. A needle is inserted into a vein in your arm and a small blood sample is withdrawn. Although one blood draw is usually sufficient, a second one may be necessary if the first is not successful. Collecting blood samples may cause fainting and some pain and/or bruising at the site on your arm where the blood was taken. In rare occasions, infection may occur. Pregnancy/Birth Control The risks of taking TEV to pregnant women or an unborn baby (foetus) are unknown. There have been studies in animals however the evaluation is ongoing. There has been no data in Women. Because of this, it is important that female participants are not pregnant or breastfeeing and do not become pregnant during the course of the study and for 7.5 months after the last dose of study drug. If you are male, you should not father a child or donate sperm for 7.5 months after the last dose of study drug. For female participants: Women must have a pregnancy test before the study starts and again just before receiving TEV If you are pregnant you cannot be in this study. You must not become pregnant during this study. If you are a woman of childbearing potential, you must use an effective form of birth control during this study and continue until 7.5 months after the last dose. Acceptable methods of birth control include: - Hormonal methods: oral contraceptive (birth control pill), an implantable contraceptive, an injectable contraceptive, intravaginal contraceptive or transdermal contraceptive. These are only considered effective if used properly and started at least 7 days prior to the first time you receive study drug. -Intrauterine device (IUD) or Intrauterine hormone releasing system (IUS) need to be in place at least 2 months prior to the first time you receive the study drug. - Barrier method (.e.g. diaphragm, condom) - Bilateral tubal occlusion and vasectomy for male partners of female patients - Sexual abstinence is only considered a highly effective method if you refrain from heterosexual intercourse in the defined period. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), your declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception. Some drugs (e.g. antibiotics) may interact with hormonal contraceptives, making them not work properly. Please inform your study doctor of all other medications you are taking. If you Page 12 of 22

13 suspect that you may have become pregnant during the study, you must contact your study doctor immediately. Your study doctor may want to follow you and the progress of your pregnancy until the baby is born and until 8 weeks after delivery. For male participants: The effects of the study drug on the male reproductive system are not known at this time, and contraceptive methods should be used throughout the study and for 7.5 months after completion of the study. It is requested that you and your partner use contraception. If you suspect your partner may be pregnant, you must contact the study doctor immediately. Your study doctor may want to follow the progress of your partner s pregnancy until the baby is born. The Sponsor would like to collect information on your partner s pregnancy, its outcome and the birth and health of the baby. Your partner will be asked to sign a separate consent form to allow her to give the study doctor information about the pregnancy and its outcome. This may include information related to your partner s health, date of conception, course of the pregnancy, medical treatments that your partner may receive and the health of the baby after birth up to 8 weeks of age. The signature of this consent is voluntary. In case your partner doesn t accept, your participation in this study will not be affected. This will help the Sponsor to understand the effects, if any, that TEV may have on your partner s pregnancy and/or unborn baby. As the risk to your partner and unborn baby are not known, it is recommended for your partner to receive appropriate prenatal care from her own doctor The information will be collected by the study doctor and the study staff and will be provided to the Sponsor to further evaluate the effect of TEV The information may also be shared with the Human Research Ethics Committee (HREC) that reviewed and approved the study and with regulatory authorities such as the TGA. 10. WHAT WILL HAPPEN TO MY TEST SAMPLES? As part of this research study, you will have a number of blood and urine samples collected for tests as described above. Your test samples will be transferred to a central laboratory chosen by Sponsor, Q2 Solutions in Singapore and the United States. Some of your samples for pharmacokinetic analysis and for antidrug antibody testing will be transferred to the bioanalytical laboratory, Teva Branded Pharmaceuticals R&D, Inc. in United States. These samples are a mandatory part of the study and samples collected will not be used for any procedures other than those outlined in this Participant Information Sheet and Consent Form. This is not an optional part of the study. If you do not wish for this to occur, you should not participate in the study. Samples collected for biomarker testing may be stored by BioStorage Technologies, GmbH, in Singapore for up to 15 years after all the participants have finished the study, after which time any remaining samples will be destroyed. This is not an optional part of the study. If you do not wish for this to occur, you should not participate in the study. All of your samples, such as blood and urine, will be key-coded. If analysed, the samples will be analysed by third-party vendors who will only receive study identifier and barcode numbers and report results for those identifiers. Only the study doctor and his/her study staff will be able to Page 13 of 22

14 link your samples to you. All information obtained from your samples will be kept confidential as stated in the What will happen to information about me? section 16 of this form. Your signature at the end of this form means that you allow the study doctor and his/her study staff to complete the set plan of study procedures (called a study protocol), including the collection of samples. Your signature also allows Teva and its authorised representatives to use these samples for tests outlined in the study protocol or for tests necessary to ensure your safety. If you stop participating in this study, Teva and its authorised representatives may continue to use the samples collected during your participation in the study for tests and procedures described in this section. The proposed blood tests include a screening test Hepatitis. This is because the study doctors need to know if you currently have Hepatitis B or C infection. You will receive information and counselling before the test. If a test shows you have Hepatitis, you will have follow-up counselling and medical advice. If your test results are positive, the study doctors are required by law to notify government health authorities. Signing the consent form means that you agree to have this testing; it will not be done without your consent. Use of Samples for Pharmacogenomic Testing (Optional) In addition to the study already described, you have the option to participate in additional research additional blood samples collected from you. If you give us permission to do so, samples collected from you may be used for pharmacogenomic testing. These samples can be used to find the genetic differences in patients and their response to study drug. DNA is the material in your body s cells (genes) that pass on characteristics that are inherited from one generation to the next (like hair and eye color). DNA is extracted from blood sample in a laboratory so that genetic information can be used to study if response to treatment with a drug, and any side effects that people may have developed, are related to their genetic identity. This area of research is called pharmacogenomics or pharmacogenetics because we are striving to understand how genes influence different responses that people have to the same drug. Samples collected for pharmacogenomic testing may be stored at BioStorage Technologies, in Singapore for up to 15 years after all the participants have finished the study, after which time any remaining samples will be destroyed. This is an optional part of the study. 11. WHAT IF NEW INFORMATION ARISES DURING THE RESEARCH STUDY? Sometimes during research we get new information about the treatment being studied. If this happens, your study doctor will tell you and discuss whether you should continue in the study. If you decide not to carry on, your study doctor will make arrangements for your care to continue. If you decide to continue in the study, doctor may ask you to sign an updated consent form. Also, on receiving new information, the study doctor might consider it to be in your best interests to withdraw you from the research study. If this happens, the doctor will explain the reasons and arrange for your regular health care to continue. 12. CAN I HAVE OTHER TREATMENTS DURING THIS RESEARCH STUDY? Whilst you are participating in this research study, you may not be able to take some or all of the medications or treatments you have been taking for your condition or for other reasons. It is important to tell your study doctor and the study staff about any treatments or medications you Page 14 of 22

15 may be taking, including over-the-counter medications, vitamins or herbal remedies, acupuncture or other alternative treatments. You should also tell your study doctor about any changes to these during your participation in the research study. Your study doctor should also explain to you which treatments or medications need to be stopped for the time you are involved in the research study. 13. WHAT IF I WITHDRAW FROM THE RESEARCH STUDY? If you decide to withdraw from the study, please notify a member of the research team before you withdraw. This notice will allow that person or the research supervisor to discuss any special requirements linked to withdrawing. If you do withdraw your consent during the research study, the study doctor and relevant study staff will not collect additional personal information from you, although personal information already collected will be retained to ensure that the results of the research study can be measured properly and to comply with the law. 14. COULD THIS RESEARCH STUDY BE STOPPED UNEPECTEDLY? Your participation in this study may be discontinued without your consent by the study doctor or the sponsoring company if you fail to follow the investigator s instructions. You may also be withdrawn from the study if, in the study doctor s opinion, the study drug is ineffective, harmful, or has medically unacceptable side effects, or for other reasons at the discretion of the Sponsor, investigator or Regulatory Agency such as the TGA. If you are withdrawn from the study, you will be asked to have the appropriate medical tests and follow-up to evaluate your health and safety. 15. WHAT HAPPENS WHEN THE RESEARCH STUDY ENDS? At the end of the research, the study doctor will evaluate treatment options (if required) specific to your circumstance. If you complete the final visit of this study, you may be offered to participate in a long-term safety study (Study TV48125-CNS-30058) and receive TEV This study will be subject to the approval of the HREC of UnitingCare Health. If you will not receive TEV for any reason or if you early withdrawal early from this study, you may still be able to participate in the long-term study. Instead of receiving study drug you will be treated with standard of care but you will still undergo study procedures related to safety and Anti-Drug Antibody evaluation. Before joining in the long term study, you will receive a separate Participant Information Sheet and Consent Form detailing all the study information and you will be asked to confirm your consent to participate by signing on the document. If you accept to participate in the long term study the first visit will take place on same day as Visit 5 (End-of-Treatment Visit (EOT) / Early Withdrawal). It is anticipated that the results of this research project will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission. PART 2 HOW IS THE RESEARCH STUDY BEING CONDUCTED? Page 15 of 22

16 16. WHAT WILL HAPPEN TO INFORMATION ABOUT ME? The Sponsor will be a data controller for personal data collected about you during the study. It is represented in Australia by Pharmaceutical Research Associates Pty Ltd. The study doctor will also be a data controller for your information, and will provide you with his/her own privacy statement. Your medical records and the information collected about you during this study will be kept confidential at Wesley Medical Research for a minimum of 15 years, as per the statutory requirement for storage of research data in Australia. Your medical records and information will be managed as follows. During the study, the study doctor will collect certain personal data about you as reasonably necessary for the conduct of the Study. This may include general personal data (for example, your initials, date of birth, gender, height, weight, racial or ethnic origin) and health information (for example, medical history and physical and mental health condition) as permitted by local laws and regulations. Health information is sometimes called sensitive personal data. Before the study doctor sends any personal data resulting from the study outside of the hospital/clinic, the information will be key-coded so that only the study site personnel can identify you personally. In addition, personal data collected in the clinical trial may be used in connection with safety and efficacy monitoring activities, product registration, reporting of adverse events, and other administrative, regulatory and legal obligations of Sponsor. Records of clinical trials, including personal data, may be sent to, inspected and/or reviewed by study site personnel, members of the Human Research Ethics Committee, representatives from Sponsor and/or Sponsor s affiliates, clinical research organisations and third party contractors working on behalf of the Sponsor, and authorised government regulatory authorities (such as the TGA) as required or permitted by law. Samples will be kept by the Sponsor in key-coded form and will only be identifiable by the coded identification number and initials assigned to each participant. Biomarker and Pharmacogenomic samples intended for genetic analyses will be stored in a country where there is an adequate level of genetic data protection (Biostorage Technologies, GmbH, Germany). All the study samples and any data generated from them can only be linked back to you by your clinical site personnel, and will be kept confidential to the extent required by applicable law. Your sample and records will only be used for investigations related to disease and response to TEV or class of drugs under study in the context of this clinical programme. Neither the study doctor nor you will receive results of this research, nor will the results be put in your health record. By signing the consent form, you are agreeing that your personal data will be collected, used, and processed as described above, as well as the transfer of key-coded data to Sponsor and/or Sponsor s affiliates and its third-party contractors, including countries where the data protection laws differ from the laws of your country. However, an adequate level of protection will apply in these countries to keep your personal data confidential. Page 16 of 22

17 In accordance with Australian privacy and other relevant laws, you have the right to request access to your personal data and, if needed, to request correction of any information which is wrong or incomplete under applicable law. This right of access and correction can be exercised through the study doctor. In the event of any publication or presentation resulting from the research, no personal data will be disclosed and your identity will remain confidential. A description of this clinical trial will be available on as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. You can withdraw your authorisation at any time. 17. COMPLAINTS AND COMPENSATION If you suffer any injuries or complications as a result of this research study, you should contact the study team as soon as possible and you will be assisted with arranging appropriate medical treatment. If you are eligible for Medicare, you can receive any medical treatment required to treat the injury or complication, free of charge, as a public patient in any Australian public hospital. There are two avenues that may be available to you for seeking compensation if you suffer an injury as a result of your participation in this research study: The pharmaceutical industry has set up a compensation process, with which the local sponsor (Pharmaceutical Research Associates Pty Ltd) of this research study has agreed to comply. Details of the process and conditions are set out in the Medicines Australia Guidelines for Compensation for Injury Resulting from Participation in a Company-Sponsored Clinical Trial. In accordance with these Guidelines, the local sponsor will determine whether to pay compensation to you, and, if so, how much. A copy of the Guidelines is available to you from the research staff on request. If you have any questions about the Guidelines, please contact Kelley Foster (Theme Leader - Neuroscience). You may be able to seek compensation through the courts. 18. WHO IS ORGANISING AND FUNDING THE RESEARCH STUDY? Teva Branded Pharmaceutical Products R&D, Inc. (Teva) is the sponsor of this study and the manufacturer of TEV This means Teva, is providing the investigational drug and financial support to the study centre and the study doctor to conduct the research study. The local Australian sponsor is Pharmaceutical Research Associates Pty Ltd. 19. WHO HAS REVIEWED THE RESEARCH STUDY? All research in Australia involving humans is reviewed by an independent group of people called a Human Research Ethics Committee (HREC). The ethical aspects of this research project have been approved by the HREC of UnitingCare Health. This study will be carried out according to the National Statement on Ethical Conduct in Human Research (2007). This Page 17 of 22

18 statement has been developed to protect the interests of people who agree to participate in human research studies. 20. FURTHER INFORMATION AND WHO TO CONTACT The person you may need to contact will depend on the nature of your query. If you want any further information concerning this project or if you have any medical problems which may be related to your involvement in the project (for example, any side effects), you can contact the principal study doctor on or any of the following people: Clinical contact person Name Michelle Cybulski Position Clinical Research Coordinator Telephone For matters relating to research at the site at which you are participating, the details of the local site complaints person are: Complaints contact person Name Kelley Foster Position Theme Leader - Neuroscience Telephone kfoster@wesleyresearch.com.au If you have any complaints about any aspect of the project, the way it is being conducted or any questions about being a research participant in general, then you may contact: Reviewing HREC name UnitingCare Health HREC HREC Executive Officer Dr Douglas Killer Telephone ethics@uchealth.com.au Page 18 of 22

19 CONSENT FORM Sponsor: Local Sponsor: Protocol No: Protocol Title: Investigator: Location: Teva Branded Pharmaceutical Products R&D, Inc. Pharmaceutical Research Associates Pty Ltd A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo Controlled, Parallel Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV versus Placebo for the Prevention of Episodic Cluster Headache Dr Nicole Limberg Wesley Medical Research Declaration by Participant: By signing my name below, I confirm the following: I have had sufficient time to read the above information, have had it explained to me in words and terms that I understand, I have been given the opportunity to ask questions, and my questions have been answered to my satisfaction. I understand the purposes, procedures and risks of the research described in the study. The physician in charge of the study will inform me of any new findings developed during the course of this study, which may affect my willingness to continue my participation. I am also authorising the use and disclosure of my personal health information. I cannot participate in this research study without this authorisation. If I refuse to give my authorisation, my medical care will not be affected. I give permission for my doctors, other health professionals, hospitals or laboratories outside this hospital to release information to Wesley Medical Research concerning my disease and treatment for the purposes of this project. I understand that such information will remain confidential. I authorise the release of my study-related medical records to Sponsor, the regulatory authorities, and the Human Research Ethics Committee I understand that I have not waived any of the legal rights that I have as a participant in a research study. I consent to the collection, use, transfer to other countries, storage of my personal information and medical data in databases and disclosure, as notified by this form, under a duty of confidentiality. I understand that my right of access and correction remain and will be possible through the Sponsor as data controller. I voluntarily agree to participate in this study. I understand I can withdraw my consent at any time. Page 19 of 22

20 I understand that I will be provided a copy of this signed consent. Please tick the one of the boxes below to indicate whether or not you agree to participate to pharmacogenomic testing I agree to participate in the Pharmacogenomics analysis Yes No Name of Participant (please print) Signature Date Name of Witness* to Participant s Signature (please print) Signature Date * Witness is not to be the investigator, a member of the study team or their delegate. In the event that an interpreter is used, the interpreter may not act as a witness to the consent process. Witness must be 18 years or older. Declaration by Study Doctor/Senior Researcher I have given a verbal explanation of the research project, its procedures and risks and I believe that the participant has understood that explanation. Name of Study Doctor/ Senior Researcher (please print) Signature Date A senior member of the research team must provide the explanation of, and information concerning, the research project. Note: All parties signing the consent section must date their own signature. Page 20 of 22

21 FORM FOR WITHDRAWAL OF PARTICIPATION Sponsor: Local Sponsor: Protocol No: Protocol Title: Investigator: Location: Teva Branded Pharmaceutical Products R&D, Inc. Pharmaceutical Research Associates Pty Ltd A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo Controlled, Parallel Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV versus Placebo for the Prevention of Episodic Cluster Headache Dr Nicole Limberg Wesley Medical Research Declaration by Participant I wish to withdraw from participation in the above research project and understand that such withdrawal will not affect my routine treatment, my relationship with those treating me or my relationship with Wesley Medical Research. Name of Participant (please print) Signature Date In the event that the participant s decision to withdraw is communicated verbally, the Study Doctor/Senior Researcher will need to provide a description of the circumstances below. Page 21 of 22

22 Declaration by Study Doctor/Senior Researcher I have given a verbal explanation of the implications of withdrawal from the research project and I believe that the participant has understood that explanation. Name of Study Doctor/ Senior Researcher (please print) Signature Date A senior member of the research team must provide the explanation of and information concerning withdrawal from the research project. Note: All parties signing the consent section must date their own signature. Page 22 of 22