1. Clinical trial identification - Information about this trial. EU trial number:

Transcription

1 Summary of Clinical Trial Results in Plain Language Thank you! Thank you for taking part in the clinical trial for the trial drug LUM001. You and all of the participants helped researchers learn if LUM001 helps people with primary biliary cirrhosis, or PBC. Shire, the sponsor of this trial, thanks you for your help and thinks it is important for you to know the results of your trial. This summary of the trial results has been prepared for you in collaboration with an independent non-profit organization called CISCRP. We hope it helps you understand and feel proud of your important role in medical research. If you have questions about the results, please speak with the doctor or staff at your trial site. 1. Clinical trial identification - Information about this trial Title of the trial: Protocol number: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in Combination with Ursodeoxycholic Acid (UDCA) in Patients with Primary Biliary Cirrhosis LUM EU trial number: National Clinical Trial Number: NCT Researchers look at the results of many trials to decide which drugs work best and are safest for the patients. It takes participants in many trials all around the world to advance medical science. This summary only shows the results from this one trial. Other trials may find different results. 2. Name and contact details of the sponsor Shire has its headquarters in Lexington, MA, USA. The phone number for general information is

2 3. General information about the clinical trial 3.1. Where was this trial done? This trial took place in 24 centers in Canada, the United Kingdom, and the United States When was this trial done? This trial started in August 2013 and ended in April Why was this trial done? Researchers were looking for a better way to treat patients with a rare liver disease called primary biliary cirrhosis or PBC. PBC slowly destroys the bile ducts in the liver. Bile is a fluid the liver makes that helps you digest food and get rid of worn-out red blood cells, cholesterol, and toxins. Bile ducts are tubes that drain bile from the liver. If the bile ducts are destroyed, the bile builds up in the liver and damages it. This can cause lasting scarring of the liver, called cirrhosis. It can also make the skin itch a lot. Doctors usually give patients with PBC a drug called ursodeoxycholic acid, which is also called ursodiol or UDCA. Ursodiol can slow PBC and help people live longer. But it does not work in all patients and it usually does not stop itching. Researchers wanted to know if the trial drug LUM001, combined with ursodiol, could help relieve itching from PBC. LUM001 blocks the body s uptake from the gut of bile acid in the gut. This might help bring down the levels of bile acids in the liver and relieve itching from PBC. The main questions researchers asked in the trial were: What side effects did participants have? Did LUM001 and ursodiol relieve itching more than a placebo and ursodiol? A placebo is a pill that looks like the trial drug but does not have any medicine in it. Did LUM001 and ursodiol help prevent liver damage more than a placebo and ursodiol? How did LUM001 affect the amount of bile acids in the blood? 4. Population of subjects - Who took part in this trial? 4.1. subjects in the trial The trial had 66 participants from 3 countries: 1 participant from Canada 18 participants from the United Kingdom 47 participants from the United States 2

3 4.2. Age group and gender breakdown A total of 66 participants, including 6 men and 60 women, took part in this trial. A total of 42 participants, including 5 men and 37 women, took LUM001. A total of 24 participants, including 1 man and 23 women, took a placebo. ranged in age from 27 to 73 years old. A total of 52 participants were under 65 years old, and a total of 14 participants were 65 or older Inclusion and exclusion criteria - Who was allowed to take part in this trial? This trial was for men and women who: Were 18 to 80 years old Had PBC with itching Were taking ursodiol Patients could not participate in this trial if they: Had other liver diseases or problems Had certain medical conditions like HIV or cancer Took certain medicines Were pregnant, breastfeeding, or planned to become pregnant 5. Investigational medicinal products used - What treatments were studied? Researchers studied LUM001 and ursodiol or a placebo and ursodiol. A placebo is a pill that looks like the trial drug but does not have any medicine in it. Using a placebo helps researchers learn if the trial drug works better than no medicine at all. Neither the participants nor the trial doctors knew which treatment each participant got. Ursodiol is also called Actigall, Dom Ursodiol Cl, PHL-Ursodiol C, PMS-Ursodiol C, Urso, Urso 250, Urso DS, and Urso Forte. All participants were in the trial for about 5 months. For 13 weeks, they took pills every day with either: LUM001 and ursodiol A placebo and ursodiol Trial doctors put participants into 1 of 2 groups by chance (like flipping a coin). 42 participants in the LUM001 Group took: Different amounts of LUM001. The amounts used were 5, 10, and 20 milligrams (mg) The same amount of ursodiol they were taking before they joined the trial 24 participants in the Placebo Group took: A placebo The same amount of ursodiol they were taking before they joined the trial 3

4 The figure below shows the 2 groups in the trial. Groups in the trial 66 participants were in the trial 42 participants took LUM001 with ursodiol 24 participants took a placebo with ursodiol 13 weeks had 6 visits to their center during the trial. During these visits, doctors checked their blood pressure, heart rate, breathing rate, and weight. They also took blood samples. answered questions about their PBC and used an electronic diary twice a day to write about their itching. One month after taking their last dose of trial drug, all participants had a final check up. 6. Description of adverse reactions and their frequency - What side effects did participants have? Adverse reactions are also known as side effects related to the treatment. Side effects are unwanted medical problems that happen during the trial. Side effects are reported because they are thought to be related to the treatments in the trial. Relatedness is reported by trial doctors for a single trial. It takes many trials to determine if a drug actually causes a side effect. Not all of the participants in this trial had side effects. A side effect is called serious if it is life threatening, puts a trial participant in the hospital, causes lasting problems, or causes a birth defect to an unborn baby. A side effect is also called serious if a person needs medical care to keep any of these things from happening. No participants died during the trial. One participant in the LUM001 group who took the 10 mg dose had a serious side effect of belly pain. No other participants had serious side effects. 4

5 Five participants stopped participating in the trial early: 2 participants stopped because of side effects 1 participant had belly pain 1 participant had diarrhea 2 participants just decided to stop participating 1 participant had to stop because she got pregnant A total of 41 participants had side effects that were not serious: 30 participants who took LUM participants who took a placebo The number of common and serious side effects observed during this trial are listed here. Side effects in this trial How many participants had serious side effects? How many participants had side effects that were not serious? How many participants stopped taking trial drug because of side effects? LUM001 5 mg Out of 1 LUM mg Out of 20 LUM mg Out of 21 Placebo Out of (5%) (100%) 14 (70%) 15 (71.4%) 11 (45.8%) 1 (100%) 1 (5%) 0 0 5

6 The table below shows the side effects that were not serious and happened in at least 4 participants during the trial. LUM001 5 mg Out of 1 Common side effects in this trial LUM mg Out of 20 LUM mg Out of 21 Placebo Out of 24 Diarrhea 1 (100.0%) 13 (65.0%) 9 (42.9%) 4 (16.7%) Nausea 1 (100.0%) 4 (20.0%) 2 (9.5%) 4 (16.7%) Upper belly pain 0 4 (20.0%) 5 (23.8%) 1 (4.2%) Belly pain 1 (100.0%) 1 (5.0%) 4 (19.0%) 1 (4.2%) Belly swelling (bloating) 0 3 (15.0%) 0 3 (12.5%) Headache (4.8%) 5 (20.8%) Indigestion 0 1 (5.0%) 1 (4.8%) 2 (8.3%) 7. Overall results of the clinical trial - What were the trial results? Below is a summary of the main questions researchers asked during this trial. Did LUM001 and ursodiol help relieve itching more than a placebo and ursodiol? No. Overall, participants in both the LUM001 and placebo groups had less itching at the end of the trial. But the average decrease in itching was about the same in both groups. Overall, the results did not show that one treatment was better than the other. The difference seen between the treatment groups could have been due to chance. rated their itching on a scale of 0 (no itching) to 10 (very severe itching) twice a day. Researchers looked at the average score for each week over 13 weeks of treatment. Itching decreased by: 26.5 points for participants who took LUM points for participants who took a placebo 6

7 The figure below shows the decreases. Decrease in amount of itching after 13 weeks No change in the amount of itching 0-5 LUM001 Group Placebo Group Amount of itching decreased Researchers also used a questionnaire to measure how bad participants itching was. The amount of change was about the same in the LUM001 and placebo groups. Did LUM001 and ursodiol help prevent liver damage more than a placebo and ursodiol? No. To see if LUM001 worked better than a placebo, researchers measured the amount of something called alkaline phosphatase (ALP) in the blood. If the liver is damaged, the amount of ALP often increases. Researchers used blood samples from participants to measure ALP. The amount of ALP in the blood was about the same in the LUM001 and placebo groups after 13 weeks of treatment. How did LUM001 affect the amount of bile acids in the blood? If the bile ducts are destroyed, the bile builds up in the liver and damages it. Bile acids are acids found in bile. In this study, researchers found that: Bile acids levels in the blood decreased over time in the LUM001 group Bile acids levels in the blood increased slightly in the placebo group Researchers also used blood samples to measure a protein that helps make bile called 7αC4. Bile helps digest food and get rid of worn-out red blood cells, cholesterol, and toxins. After 13 weeks of treatment, the amount of 7αC4 in the blood: Increased in the LUM001 group Decreased in the placebo group 8. Comments on the outcome of the clinical trial - What is important to know about these results? LUM001 did not help relieve itching from PBC more than a placebo in this trial. Bile acids in the blood were slightly reduced by LUM001. 7

8 Some participants had side effects like diarrhea, nausea, and abdominal pain. Only 1 participant had a serious side effect. These results are only for the participants in this trial and may be different for other people with PBC. The results for any individual could have been better or worse than the overall results for the group. Also, no single clinical trial can give a complete picture of the benefits and risks of an experimental treatment. Other trials may find different results. It takes many trials to know whether a drug might one day be a treatment option for certain patients. 9. Indication if follow up clinical trials are foreseen - Will there be more trials with this drug? There are no other trials with LUM001 now in patients with PBC. LUM001 is currently being tested in patients with other liver diseases. 10. Indication where additional information could be found - Where can I learn more about this trial? You can find more information about this trial at: Thank you It is said that the greatest gift is one which is given anonymously, giving when you do not know whether you will get direct personal benefit. This is the gift that you have given by taking part in a clinical trial. It is a brave and selfless act, one that advances medical knowledge and benefits public health. Thank you for the gift of your participation in clinical research. The Center for Information & Study on Clinical Research Participation (CISCRP) is a non-profit organization focused on educating and informing the public about clinical research participation. CISCRP is not involved in recruiting patients for clinical trials, nor is it involved in conducting clinical trials. CISCRP 56 Commercial Wharf East, Boston, MA MED-HERO 8