The Regenerate Study
Research type
Research Study
Full title
A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects with Nonalcoholic Steatohepatitis
IRAS ID
186697
Contact name
Shawn Sheeron
Contact email
Sponsor organisation
Intercept Pharmaceuticals, Inc
Eudract number
2015-002560-16
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 8 months, 1 days
Research summary
Summary of Research
This study will evaluate the Safety and Efficacy of Obeticholic Acid (OCA) in Subjects with Nonalcoholic Steatohepatitis (NASH).
NASH is a serious, chronic liver disease with a large unmet medical need and no approved treatments. The incidence of NASH is increasing and NASH is likely to be the leading cause of liver transplant by 2020.
In view of the serious nature of the disease, the increasing number of patients, the complications that arise from the disease,and the unmet medical need, approved therapy for NASH is needed.
The Sponsor of this study, Intercept Pharmaceuticals, Inc., wants to study the investigational drug OCA and its effect on NASH.
OCA, is a modified (manmade) version of a compound made in the liver called a bile acid. Bile acids are used by the body to help with digestion and have additional effects on liver function. This study will look at the effect of OCA onimprovements in the condition of liver tissue for patients with NASH, all-cause mortality, and liver-related clinical outcomes.
Up to 300 medical centers in Latin America, North America, Asia Pacific Region and Europe are expected to participate in this study.
Subjects will be screened for a period of up to 12 weeks before entering the study. Approximately 2065 subjects (globally) with NASH will be randomized to receive OCA 10 mg, OCA 25 mg, or matching placebo in a 1:1:1 ratio for the duration of the study, in conjunction with local standard of care.
Once participation in the study is confirmed, patients will attend the clinic 8 times for the first 18 months they are in the study and then 2 times per year (every 6 months) for each additional year they are in the study.
The expected duration of this study is approx. 6 years.
Intercept Pharmaceuticals, Inc., a drug company, is funding the study.Summary of Results
OVERVIEW • In this study, researchers tested an experimental drug called obeticholic acid (OCA) to see how treatment with OCA compared to placebo in patients with Nonalcoholic Steatohepatitis (NASH), had any effect on all causes of death and liver-related clinical outcomes which occurred over the study.
• 825 participants received 10 mg OCA, 827 participants received 25 mg OCA, and 825 participants received placebo.
• At the end of the study, researchers found that there was not a major difference between the treatment groups and placebo with respect to how long it took for patients to suffer death or a significant liver event. There was a difference in how the patients responded to the medicine between the groups but was not significant.
• 2380 participants had one or more side effect during the study, and 709 had one or more serious side effect. 28 participants died while participating in the study.THANK YOU!
At Intercept, we think it is important for you to know the results of your study. We hope it helps you understand the important role you 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?
Nonalcoholic steatohepatitis (NASH) is a form of liver disease where the liver becomes inflamed and damaged due to a build-up of fat, causing scar tissue (called ‘fibrosis’) in the liver. It is a part of a group of conditions called nonalcoholic fatty liver disease. NASH, when left untreated, can progress to advanced scarring (called ‘cirrhosis’), liver failure, liver cancer, and liver-related death.NASH is now referred to as metabolic dysfunction associated steatohepatitis, or “MASH”.
Despite the seriousness of this disease, especially when advanced scarring is present, there is only 1 recently approved medicine available. Most current treatment is supportive, concentrating on managing complications, and as a last resort, liver transplantation.
Obeticholic acid (OCA) is a modified bile acid and farnesoid X receptor agonist, meaning that it has effects on bile acids and fat and sugar metabolism. It is possible that OCA can affect the formation of scarring in the liver and has some protective ability against bile acid-caused liver cell damage.
This study included:
• Three groups of participants which were randomly assigned to one of the following groups:
1) a once daily dose of 10 mg OCA
2) a once daily dose of 25 mg OCA
3) a placebo taken once dailyPlacebo is a treatment that looks like the study drug but has no active drugs in it. Using a placebo helps researchers learn if the study drug works better than no treatment at all.
This study had 2 parts: a screening part, and a double-blind, placebo-controlled part.
• In the double-blind part of the study, neither the participants nor the study doctor could choose the medicine the participants received. Participants agreed to be put into a medicine group by chance (“randomized”). This is like flipping a coin or drawing numbers out of a hat.
o This was done to make sure the study results were not influenced in any way.The main purpose of this study was to assess the effect of OCA compared to placebo.
The main question researchers asked in this study was:
What is the effect of OCA compared to placebo on all causes of death and liver-related clinical outcomes between the time the participant entered the study and the first time one of these events happened.The clinical outcomes included: a change in how bad the liver damage is, if the participant needed a liver transplant, if the participant was hospitalized for 24 or more hours due to liver-related complications, a fluid build-up in the belly due to liver damage, or progression of the liver scarring confirmed by microscope.
HOW A MEDICINE IS DEVELOPED –
Phase 1: In Phase 1 studies researchers look at the study drug to learn what happens to it in the body.
Phase 2: In Phase 2 studies researchers try to find out if a study drug could be effective in patients with a particular health condition.
Phase 3: In Phase 3 studies researchers compare the study drug to a standard treatment or placebo. This was a Phase 3 study.
Phase 4: Phase 4 studies are done to learn about the effects of the drug in a larger number of people.WHO WAS IN THE TRIAL?
Men and women aged 18 years and over who had a confirmed diagnosis of NASH with the presence of all 3 key findings, based upon the NASH Clinical Research Network (CRN) scoring system, diagnosed by a liver biopsy not more than 6 months before the study start, were invited to participate.• The NASH CRN score is a standardized score based on three areas. When you add up the total, if you have a score of five or more, it is “definite NASH”:
o The amount of fat in the liver is (steatosis) is scored from 0 to 3 o The amount of inflammation in the liver (lobular inflammation) is scored from 0 to 3 o The amount of swelling of the liver cells (hepatocellular ballooning) is scored from 0 to 2Patients also needed to have evidence of liver scarring (fibrosis).
2477 participants were enrolled in the study and received 1 or more doses of OCA or placebo.
1030 (42%) were men and 1447 (58%) were women; most patients (1964, or 79%) were 64 years or younger, with 516 (21%) being aged 65 to 84 years.This study took place at over 300 study centers across Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, United Kingdom, and the United States.
The numbers of participants in each country are shown below:
NORTH AMERICA; United States 1090; Canada 92.
EUROPE: Austria 11; Belgium 29; Denmark 24; Finland 16; France 126; Germany 75; Hungary 11; Israel 31; Italy 71; Poland 16; Portugal 13; Serbia 6; Spain 82; Sweden 11; Switzerland 21; United Kingdom 112.
AUSTRALASIA: Australia 69; New Zealand 20.WHAT TREATMENT DID PARTICIPANTS GET?
The basic design of this study is shown here:
SCREENING
GROUPS (Randomised):
OCA 10mg (once daily) 825 participants – Double Blind Treatment OCA 10mg OCA 25mg (once daily) 827 participants – Double Blind Treatment OCA 25mg Placebo (once daily) 825 participants – Double Blind Treatment PlaceboParticipants were assigned to each treatment by chance (“randomized”):
• Group 1: 825 participants were assigned to get 10 mg of OCA once daily.
• Group 2: 827 participants were assigned to get 25 mg of OCA once daily.
• Group 3: 825 participants were assigned to get placebo once daily.HOW LONG DID THE STUDY LAST?
Participants were supposed to be treated until the end of the double-blind phase. The study was initially planned to run for approximately 7 years.
The study began in December 2015 and ended earlier than planned in September 2023 due to business reasons. The study was not stopped because of safety reasons.WHAT WERE THE STUDY RESULTS?
The main question the researchers asked was, what is the effect of OCA compared to placebo on deaths from all causes and other negative outcomes related to the liver between the time the participant entered the study and the first time of one of these events happened?There was no major difference in the percentage of all causes of death and liver-related events in the participants taking OCA compared to placebo. There was a difference in the response that patients had across the treatment groups, but this was not significant.
Percentage of participants who had died or had a liver-related event:
Placebo (825 participants) – 19%
OCA 10mg (825 participants) – 16%
OCA 25mg (827 participants) – 15%This does not mean that everyone in this study had these results, 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 at 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. They may or may not be related to the medicine tested in the study. Side effects are also known as “adverse events.” Not all the participants in this study had side effects.Side Effects During the Study:
Placebo group there were 825 participants.
OCA 10mg Group there were 825 participants OCA 25mg group there were 827 participantsHow many participants had serious side effects?
Placebo 216 (26%); OCA 10mg 245 (30%); OCA 25mg 248 (30%)How many participants had non-serious side effects?
Placebo 772 (94%); OCA 10mg 795 (96%); OCA 25mg 813 (98%)How many participants died from side effects?
Placebo 9 (1%); OCA 10mg 8 (1%); OCA 25mg 11 (1%)How many participants stopped taking the study medicine because of side effects?
Placebo 111 (14%); OCA 10mg 118 (14%); OCA 25mg 206 (25%)
2380 participants (96%) had one or more side effects during the study.The table below shows the most common side effects that happened during the study.
The Most Common Side Effects
Itching: Placebo 207 (25%); OCA 10mg 289 (35%); OCA 25mg 466 (56%) An increase of ‘bad’ cholesterol: Placebo 83 (10%); OCA 10mg 172 (21%); OCA 25mg 180 (22%) Feeling sick: Placebo 141 (17%); OCA 10mg 140 (17%); OCA 25mg 156 (19%)
COVID-19 infection: Placebo 155 (19%); OCA 10mg 155 (19%); OCA 25mg 117 (14%)
Tiredness: Placebo 130 (16%); OCA 10mg 143 (17 %); OCA 25mg 128 (16%) Urinary tract infection: Placebo 120 (15%); OCA 10mg 125 (15%); OCA 25mg 124 (15%) Stomach pain: Placebo 123 (15%); OCA 10mg 125 (15%); OCA 25mg 123 (15%)
Constipation: Placebo 81 (10%); OCA 10mg 112 (14%); OCA 25mg 125 (15%) Back pain: Placebo 113 (14%); OCA 10mg 126 (15%); OCA 25mg 95 (12%) Joint pain: Placebo 127 (15%); OCA 10mg 105 (13%); OCA 25mg 115 (14%)
Diarrhoea: Placebo 139 (17%); OCA 10mg 108 (13%); OCA 25mg 92 (11%) Diabetes mellitus: Placebo 85 (10%); OCA 10mg 100 (12%); OCA 25mg 88 (11%) Upper stomach pain: Placebo 92 (11%); OCA 10mg 89 (11%); OCA 25mg 94 (11%) High blood pressure: Placebo 80 (10%); OCA 10mg 96 (12%); OCA 25mg 81 (10%) Nose and throat infection: Placebo 79 (10%); OCA 10mg 78 (10%); OCA 25mg 96 (12%) Increased fats in the blood: Placebo 26 (3%); OCA 10mg 71 (9%); OCA 25mg 88 (11%)WHAT SERIOUS SIDE EFFECTS DID PARTICIPANTS HAVE DURING THE STUDY?
Some side effects are considered “serious,” which means they may be life-threatening, cause long-term problems, or cause a person to need hospital care.709 participants (29%) had 1 or more serious side effect during the study.
Most of the serious side effects were reported in fewer than 5 participants in each group; the events which were reported more than 5 times within a group were: sudden damage to the kidneys (11 times in OCA 25 mg, 6 times in OCA 10 mg); viral lung infection (9 times in OCA 25 mg, 8 times in OCA 10 mg); inflammation of the gall bladder (9 times in OCA 25 mg); gall stones (8 times in OCA 25 mg); breakdown of flexible tissue (7 times in OCA 25 mg); COVID-19 infection (6 times in OCA 25 mg); chest pain unrelated to the heart (6 times in OCA 25 mg); pancreatitis (6 times in OCA 25 mg group); blood stream infection (7 times in placebo group, 7 times in OCA 10 mg); stomach pain (7 times in OCA 10 mg); cancer of the liver cells (7 times in OCA 10 mg); herniated disc (6 times in placebo group).
28 (1%) participants died during the study; 9 participants (1%) were in the placebo group, 8 (1%) were in the OCA 10 mg group, and 11 (1%) were in the OCA 25 mg group.
Most events leading to death were reported only once, the events which were reported more than once overall were: sudden damage to the kidneys, (1 in the OCA 25 g group, 1 in the OCA 10 mg group); COVID-19 infection (2 in the OCA 25 mg group); death due to unknown cause (2 in the OCA 25 mg group); viral lung infection (2 in the placebo group, and 2 in the OCA 25 mg group); suicide (2 in the placebo group and 1 in the OCA 10 mg group).
This report only shows the most frequently reported side effects and serious side effects that happened during the study. Information about other side effects 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%7C02%7Csheffield.rec%40hra.nhs.uk%7Cc390f0930caf4ea1924808dcd34e781f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638617581173052420%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=EMHuljnmu9hABPZI2P%2Fx%2F1j9DwdCv%2FGXsFq8UlUl8x4%3D&reserved=0 Use the study identifier NCT02548351
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Csheffield.rec%40hra.nhs.uk%7Cc390f0930caf4ea1924808dcd34e781f%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638617581173061379%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=Qrncl7i8AF6%2F88JL4V0QfvY4IIxYjtWVgCTto5%2FKDD8%3D&reserved=0 Use the study identifier 2015-002560-16 Intercept Study ID: 747-303Thank you again for being a part of this study.
We do research to try to find the best ways to help patients, and you helped us do that.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
15/YH/0478
Date of REC Opinion
10 Dec 2015
REC opinion
Further Information Favourable Opinion