A Dose Finding Study In Pediatric Subjects With Biliary Atresia.
Research type
Research Study
Full title
A Multicenter, Randomized, Open-Label, Single- and Multiple-Dose, Dose Finding Study and Open-Label Extension to Assess the Effects of Obeticholic Acid in Pediatric Subjects with Biliary Atresia
IRAS ID
170862
Contact name
Linda Robertson, PhD
Contact email
Sponsor organisation
Intercept Pharmaceuticals, Incorporated
Eudract number
2014-004693-42
Duration of Study in the UK
1 years, 7 months, 31 days
Research summary
Research Summary
Biliary atresia is a disease where children are born without a duct connecting the gall bladder to the intestine. The gall bladder makes bile, which is important for digestion. Without this duct, bile builds up and damages the liver. Surgery (hepatoportoenterostomy; Kasai) to repair the duct helps, but children still may experience long-term liver damage, and many eventually need a liver transplant.
The overall goal of the clinical program is to see if the study drug, obeticholic acid (OCA) helps prevent liver damage after the repair surgery. This study is the first of three planned clinical studies in biliary atresia using OCA as the study drug. It will determine the safety of this drug in children, and how the drug is absorbed and retained by the body. The study will also measure if the drug has an effect on liver health, and if this effect is related to how much drug is taken. The study will measure levels of the drug in the body after a single dose, and also after taking the drug multiple times (once a day for 8 weeks).
This study will compare the liver health of subjects who receive the study drug to subjects who do not receive study drug. Approximately 60 subjects will be enrolled in this study. Of those 60 subjects, there will be some subjects who are randomly assigned by a computer to receive OCA (the “OCA treated” group), and some who are randomly assigned to not receive OCA (the “non-OCA treated” group). All subjects will be able to stay on medication, if any, that they are currently taking.
The safety of the drug will be measured by a doctor examining the subject and asking about his or her health, for example, any side effects he or she might be experiencing. In OCA treated subjects, the levels of the drug in the body will be measured by drawing a small amount of blood at specific times after the subject has taken the drug, and measuring the amount of drug in the blood sample using a laboratory test.
It is important to note that the non-OCA treated subjects will not participate in the drug measurement blood sample collection in order to avoid undue pain to the subject. All subjects will have their liver health measured by laboratory tests run on blood and urine samples.
There will be three possible dose of the drug, and the study will start by testing the lowest dose first. Once the low dose is determined to be safe, after a thorough review of 4 subjects, then the medium dose group can start to be enrolled. Once the medium dose group has been determined safe, then the high dose group can start to be enrolled. Additionally, the dose will be tailored to the weight of the pediatric subject, so they will not receive a dose that is too high for them.
This study will begin by testing children who are 2 years of age to less than 18 years of age. The results from these older children will help determine if the study doses should change for younger subjects (0 to less than 2 years of age). The first subjects will be children who are able to swallow a tablet with the correct dose for their weight. Later, the drug will be made in liquid form to be given to babies or those who cannot swallow tablets.
After subjects complete the study, they may be able to continue taking the study drug once the Sponsor has initiated this phase of the study. This phase should be approved in the next protocol amendment. All subjects will be eligible to take the drug at this point, even if they were in the group that did not receive study drug previously.Summary of Results
OVERVIEW • In this study, researchers tested an experimental drug called obeticholic acid (OCA) to see how safe and how well tolerated, and blood levels a single dose and multiple doses were in children with biliary atresia.
• 8 participants were enrolled, with 7 receiving 1 or more doses of OCA.
• The study ended earlier than planned, so only the safety of the medicine was analyzed.
• 4 out of the 8 participants had side effects related to the medicine tested in the study. No participants had serious side effects related to the medicine tested in the study; 1 participant stopped taking the study medicine because of a side effect, and no participants died during the study.At Intercept, we think it is important for you to know the results of your, or your child’s study. We hope it helps you understand the important role you and your child played in supporting medical research.
This is a summary of the main results of your study. If you have questions about these results, the doctor or staff at your study site may be able to answer them.
WHY WAS THIS STUDY DONE?
Biliary atresia is a condition in infants in which the bile ducts outside and inside the liver are scarred and blocked. Bile can’t flow into the intestine, so bile builds up in the liver and damages it. The damage leads to scarring, loss of liver tissue, and function. Biliary atresia is the main indication for liver transplantation in children. However, why it occurs needs more research.The current treatment for biliary atresia is a surgery called hepatoportoenterostomy (HPE). There are no approved medicines, though sometimes medicines such as ursodeoxycholic acid (UCDA), steroids, and antibiotics are used to improve bile flow and reduce inflammation in the bile duct.
OCA has been shown to increase bile flow and have liver-protective properties.
OCA is a tablet which is taken by mouth.
This study included:
• A placebo during the 2-week screening period to see if you or your child can swallow the tablets. o A placebo is identical in size and shape to the study medicine but does not contain any medicine.• OCA in a single dose and in multiple doses.
The main purpose of this study was to assess the safety, tolerability, and blood levels of OCA.
The main questions researchers asked in this study were:
1. How safe is OCA, and how well is it tolerated? To study this, researchers looked at how many participants had side effects. They also measured blood levels of OCA after a single dose and at set time periods after multiple doses to see how the blood levels of OCA and associated products (called “conjugates”) changed.WHAT HAPPENED DURING THE STUDY?
Phase 2 – In Phase 2 studies researchers try to find out if a study drug could be effective in patients with particular health condition This trial was Phase 2 studyWHO WAS IN THE TRIAL?
Boys and girls aged 2 and over to less than 18 years, who had biliary atresia, a successful HPE, and were able to swallow tablets were invited to participate.8 participants entered the study and 7 participants received 1 or more doses of OCA.
• 1 participant was a boy and 7 were girls.
• 4 participants were aged 2-11 years; 4 were aged 12-17 years.This study was done at study centers in Belgium, Denmark, and the United Kingdom.
WHAT TREATMENT DID PARTICIPANTS GET?
Participants were enrolled in the Single Dose (SD) and Multiple Dose (MD) low dose cohort. If they were suitable, they could also participate in an open-label extension (OLE) study. No participants were enrolled in the medium or high dose groups.
This was an open-label study, which means that both the researchers and the participants knew what treatment they received.HOW LONG DID THE STUDY LAST?
Participants were supposed to be treated until the end of the OLE phase. Of the 8 participants who entered the study, 6 left the study before its end:
• 1 participant did not take any study medication and was a ‘control’ subject. This participant was discontinued from the MD part by their doctor.
• 1 participant discontinued due to not taking the study medicine according to the protocol (non-compliance).
• 1 participant discontinued due to an interrupted supply of the study medicine from the Sponsor.
• 1 participant was discontinued by the Sponsor due to high OCA levels in the blood.
• 1 participant discontinued due to high lipase (pancreas enzyme) in the blood.
• 1 participant was discontinued by their doctor.2 participants were still taking part when the Sponsor ended the study.
The study began 29 January 2016 and ended 09 March 2023. The study ended earlier than planned due to slower than expected enrollment.WHAT WERE THE STUDY RESULTS?
Was the medicine safe and well tolerated?
Because the study ended early, only the safety part was analyzed. The side effects experienced by the participants are in the next section.
This does not mean that everyone in this study had the same experience, and individual results could be better or worse than the overall group. Other studies may have different results. These are just some of the main results of this study. More results may be available on the websites listed at the end of this summary.
WHAT SIDE EFFECTS DID PARTICIPANTS HAVE DURING THE STUDY?
Side effects are unwanted health problems that happen during the study. Side effects that are thought to be related to the medicine tested in the study are reported here. Side effects are also known as “adverse effects” or “adverse reactions.” Not all the participants in this study had side effects.
4 participants had one or more side effects reported during the study. The table below shows the most common side effects that happened during the study.
The Most Common Side Effects
Low Dose
(7 Participants taking study medicine)
Headache 2
Itching 1
Symptoms of depression 1
Tiredness 1
Increased bilirubin in the blood 1WHAT SERIOUS SIDE EFFECTS DID PARTICIPANTS HAVE DURING THE STUDY?
Some side effects are considered “serious,” which means they may cause a person to need hospital care, may be life-threatening, or may cause long-term problems.
No participant had a serious side effect which was related to the medicine being studied during the study. No participants died during the study.
This report only shows the most frequently reported side effects and serious side effects that happened during the study. Information about other side effects or medical problems may be available at the websites listed at the end of this summary.WHERE CAN I LEARN MORE ABOUT THIS STUDY?
Researchers will use the information from this study and other similar studies to help determine if OCA is safe and well tolerated. Additional studies with OCA are ongoing.
For more information about this study, check these websites:
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Cedgbaston.rec%40hra.nhs.uk%7Cf90616a8c3b6426620c808dbb2d40cc3%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638300396033459345%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=baBD3TGT6dGd8u3H3eGbgctMf%2BDFPI1p9hXgm8re%2B9c%3D&reserved=0 Use the study identifier NCT05321524
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Cedgbaston.rec%40hra.nhs.uk%7Cf90616a8c3b6426620c808dbb2d40cc3%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638300396033459345%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=sLl2%2BSuZGg4gsEvEcAGr%2FOOs%2B4wWVWzQPl6pjr8LMGo%3D&reserved=0 Use the study identifier 2014-004693-42 Intercept Study ID: 747-206 Date of This Report: 31 August 2023Thank you again for being a part of this study!
We do research to try to find the best ways to help patients, and you, and your child, helped us to do that.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
15/WM/0015
Date of REC Opinion
6 Mar 2015
REC opinion
Further Information Favourable Opinion