A FIH SAD/MAD Study in A3907
Research type
Research Study
Full title
A Phase I, Interwoven, First-in-Human, Double-blind, Single and Multiple Ascending Dose Study in Healthy Adult Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of A3907, a First-in-class IBAT Inhibitor
IRAS ID
288699
Contact name
Ashley Brooks
Contact email
Sponsor organisation
Albireo
Eudract number
2020-004423-17
Clinicaltrials.gov Identifier
20/NE/0216, REC Ref
Duration of Study in the UK
0 years, 9 months, 26 days
Research summary
Summary of Research
A3907 is an oral potent inhibitor of the apical sodium bile acid transporter (ASBT; also referred to as ileal bile acid transporter). Bile acids are synthesized in the liver from cholesterol and excreted into the small intestine via the gallbladder. A3907 is being investigated in this first-in-human study in support of subsequent clinical development in liver diseases including non-alcoholic steatohepatitis (NASH). ASBT inhibition has been shown to reduce low density lipoprotein cholesterol (LDL-C) levels, and so ASBT inhibition may also improve NASH associated disease risk.\n\nPart A\nPart A is a double-blind, randomized, placebo-controlled, single ascending dose (SAD), sequential group design. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Each subject will participate in 1 treatment period only. Subjects will reside at the clinical research unit (CRU) from Day -2 (2 days before dosing) to Day 4 (3 days [72 hours] after dosing). All subjects will have a follow-up phone call on Day 7 ± 1 and return for a follow-up visit on Day 10 ± 1.\n\nPart B\nPart B is a double-blind, randomized, placebo-controlled, interwoven, multiple ascending dose (MAD) design. Part B may start after completion of Group A3, at a dose where the predicted exposure is not expected to exceed an exposure shown to be safe and well tolerated in Part A. The MAD groups will be dosed sequentially within Part B, but may be interwoven with the SAD Group A4 and beyond. Part A: 48 subjects will be studied in 6 groups (Groups A1 to A6). One optional group of 8 subjects may be added (Group A7). Part B: 32 subjects will be studied in 4 groups (Groups B1 to B4). Up to 2 optional groups of 8 subjects may be added (Groups B5 and B6).\nSummary of Results
CLINICAL TRIAL RESULTS SUMMARY A FIH SAD/MAD Study in A3907 THANK YOU!
Thank you to those who participated in this research trial for A3907. Without trial participants, drug development would not be possible. Participation in this trial has helped the researchers learn how A3907 works and how safe it is to use.
The trial information given in this summary is from one trial only and must not be used to make medical decisions. This drug is not yet approved for marketing, and the outcomes of this trial may not apply to all patients. Do not change your current medical treatment without consulting your doctor.
WHAT WAS THE PURPOSE OF THIS CLINICAL TRIAL?
This trial was designed to learn about any potential side effects of A3907 treatment.
HOW WAS THIS TRIAL DONE?
Who took part in this trial?
This trial included 67 healthy men and 8 healthy women between the ages of 18 and 60 years.Where did this trial take place?
This trial took place in the United Kingdom.When did this trial take place?
This trial started in February 2021 and ended in September 2021.What treatments were tested in this trial?
This trial studied A3907 capsules compared to a placebo by mouth. A placebo is an identical looking capsule that does not have any medical ingredients in it.What has been completed?
Before treatment, the trial doctor checked the health of every person to ensure they could be in the trial.
This trial was done in 2 parts. In both parts of the study, people were split into 2 treatments. Around 3 in every 4 people took A3907 and around 1 in every 4 people took placebo. The treatment a person was given was determined by chance (randomised) to reduce differences between the treatments. Reducing differences between the treatments makes the comparison between the treatments fairer.
This trial was also “double-blinded.” This means that neither the people taking part in the trial nor doctors knew who was given which treatment. This was done to make sure that the trial results were not influenced in any way.The first part of the trial had 7 groups that were given their treatment one time. A different dose of trial medicine (A3907) was tested in the first 6 groups, starting at the lowest strength in the first group. The sixth and seventh groups got the same dose of trial medicine. Each group started with 1 person getting A3907 and 1 person getting placebo. Two days later, the trial doctor reviewed their medical tests and what side effects, if any, these people got. If there were no safety concerns in these 2 people, the rest of the people in that group were treated. People stayed in the clinic for 4 days, from the day before treatment until 2 days after treatment. They returned to the clinic 7 days later for an additional check-up.
The second part of the trial had 3 groups that were given their treatment once a day for 7 days. A different dose of trial medicine was tested in each group, starting with the lowest strength in the first group. People stayed in the clinic for 10 days, from the day before treatment started until 2 days after treatment ended. They returned to the clinic 7 days later for an additional check-up.
Blood tests were done to see how much medicine was in the blood. The trial doctor checked for any side effects from the medicine. After each group completed, researchers reviewed the amount of medicine in people’s blood, blood tests, vital signs, the electrical activity of their heart, and what side effects they got to decide if the next planned group could be treated and what strength of trial medicine to give to this next group.
WHAT ARE THE MAIN RESULTS OF THIS TRIAL?
The purpose of this study was to learn about any potential side effects of A3907 treatment. A3907 was well tolerated when administered as one and multiple doses. There were no serious side effects during the study. There were some nonserious side effects as described below.
WHAT WERE THE SIDE EFFECTS?
In this trial, some people experienced side effects. Side effects are unwanted medical events that happen during the trial that the trial doctor (investigator) thinks could have been caused by the treatments in the trial. Not all the people in this trial had side effects. All of the side effects that happened in this study were mild.In the first part of the trial when people were treated one time, there were more side effects in people treated with the 2 highest doses of A3907 than in people treated with placebo. In these groups:
• Between 3 out of 5 people (60.0%) and 5 out of 6 people (83.3%) had side effects after A3907
• 4 out of 14 people (28.6%) had side effects after placebo
The most common side effects in people treated with A3907 one time were:
• 12 out of 39 people (30.8%) had diarrhoea after A3907
• 3 out of 39 people (7.7%) had stomach pain after A3907
Stomach pain side effects were more common in people treated with A3907 compared to people treated with placebo:
• 3 out of 39 people (7.7%) had stomach pain after A3907
• 0 people had stomach pain after placeboIn the second part of the trial when people were treated for 7 days, in all 3 groups there were more side effects in people treated with A3907 than in people treated with placebo:
• Between 1 out of 5 people (20.0%) and 6 out of 6 people (100%) had side effects after A3907
• 0 people had side effects after placebo
The most common side effects in people treated with A3907 for 7 days were:
• 10 out of 17 people (58.8%) had diarrhoea after A3907
• 4 out of 17 people (23.5%) had headache after A3907
Both of these side effects were more common in people treated with A3907 compared to people treated with placebo.
WHAT WAS LEARNED FROM THIS TRIAL?
The side effects that happened in this study were mild enough that A3907 should be studied further.
WHERE CAN I FIND MORE INFORMATION ABOUT THIS TRIAL?
Results from this trial may be presented in a different way in other documents.
Trial Title A Phase I, Interwoven, First-in-Human, Double-Blind, Single and Multiple Ascending Dose Study in Healthy Adult Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of A3907, a First-in-Class IBAT Inhibitor
Public Trial Title A FIH SAD/MAD Study in A3907
Protocol Number A3907-001
Eudra CT Number 2020-004423-17
Study Sponsor Albireo AB https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.albireopharma.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C34a1020595f54074fd3e08da8a82534d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637974589594062524%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=1Gdskol6goPTpqnY1sHgYboDOmom4XAJkhpGGUEIdYA%3D&reserved=0
Please email any questions to medinfo@albireopharma.com This trial was registered on ISRCTN ARE THERE PLANS FOR FURTHER TRIALS?
There are currently no ongoing trials with A3907, but additional trials with A3907 are being planned.REC name
North East - York Research Ethics Committee
REC reference
20/NE/0216
Date of REC Opinion
16 Nov 2020
REC opinion
Further Information Favourable Opinion