IMC-I109V-101
Research type
Research Study
Full title
An Open-label Study Evaluating the Safety, Antiviral Activity, and Pharmacokinetics of IMC-I109V in HLA-A*02:01 Positive Patients with Chronic HBV who are Non-Cirrhotic, Hepatitis B e Antigen-negative, and Virally Suppressed
IRAS ID
283967
Contact name
Kaushik (Kosh) Agarwal
Contact email
Sponsor organisation
Immunocore Ltd,
Eudract number
2019-004212-64
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 3 months, 0 days
Research summary
This study will be performed in adult male and female participants with chronic hepatitis B virus (HBV) infection (CHB) and who are receiving long-term nucleoside analogue (NA) therapy.
The study is sponsored by Immunocore Ltd, UK.
This is a first in human study which means this is the first time the study drug has been tested in people.
The study drug being investigated is called IMC-I109V. IMC-I109V has been developed to treat HBV by activating the body’s own immune system to fight the virus. The study drug has 2 parts. The first part, called a “T cell receptor”, sticks very tightly to virus cells that make markers called “HLA-A*02:01”. The second part, called “anti-CD3 scFv”, sticks to a T cell (a type of white blood cell that helps protect the body against disease). IMC I109V makes the T cell stick to the hepatitis virus cell, which then sends a signal to attack the virus.
The purpose of this study is to find out how safe and effective IMC-I109V is for treating CHB.
The study will be divided into two parts: Part 1 Single Ascending Doses (SAD); and
Part 2 Multiple Ascending Doses (MAD).
The duration of the entire study period will be:
Part 1 - SAD will be approximately 10 weeks for each participant, comprising a maximum 42-day screening period, a 1-day treatment period involving a single administration of IMC-I109V and a 28 day follow-up period, for a total of 9 visits.
Part 2 - MAD will be approximately 54 weeks for each participant, comprising a maximum 42-day screening period, a 24-week treatment period involving weekly administration of IMC-I109V, and a 24-week follow-up period, with a total of 30 visits.
Participants will be enrolled in various countries as follows: New Zealand, Australia, Hong Kong, South Korea, Romania, Belgium, Poland, UK, Spain and Ukraine.Lay summary of study results: The IMC-I109V-101 study was an early clinical trial carried out at hospitals in Australia, Belgium, Hong Kong, Poland, Romania, South Korea, Spain and the United Kingdom (UK). The UK sites were Nottingham University Hospital, Chelsea & Westminster Hospital, Oxford University Hospitals NHS Trust and Guy’s and St Thomas’ Hospital.
This study tested a new experimental drug, IMC-I109V, for hepatitis B, a virus that causes serious liver damage and cancer. Standard treatments for hepatitis B keep the virus in check but rarely clear it from the body. IMC-I109V was designed to help the immune system target and kill the cells in the liver where hepatitis B hides.
The study had 3 parts. The first two parts were for people with chronic hepatitis B who met certain criteria, and the third part was for people with hepatitis B-related liver cancer. However, only the first part of the study was completed. The company decided not to continue with the next parts because it was not practical to proceed at this time. This study started in May 2021 and ended in December 2024.
In this study, researchers looked at how a single dose of IMC-I109V works in people with chronic hepatitis B. Researchers did tests on men and women before and after they were given IMC-I109V to find out:
- if there were any unwanted side effects
- how the body processed the drug
- what effects the drug had on the immune system
- what effects the drug had on levels of hepatitis B markers in the blood.The study included adults aged 18 to 65 who had chronic hepatitis B without liver cirrhosis, who were already taking standard hepatitis B medication. Only people with a certain genetic marker (HLA-A*02:01) could take part, as this marker is necessary for the drug to work. The other main criteria that allowed participation in the study were: testing negative for a marker of high viral activity (hepatitis B e antigen), having a low level of another viral marker (hepatitis B surface antigen, or HBsAg, which is the outer coat of the virus) and having normal or near-normal tests for liver health. These criteria were chosen to ensure that the chance of severe side effects due to the drug would be as low as possible.
Participants were given IMC-I109V through a drip into the vein and stayed under medical supervision in hospital for one night. Researchers closely watched for any side effects for 24 hours after the infusion. The participants then had check-ups, including tests for liver health, the following day and then once a week for four weeks.Twenty people took part in the study (17 men and 3 women); 5 (25%) were from the UK. They were placed in 4 groups, which each received a different single dose of IMC-I109V, starting with a low dose that was gradually increased for each group. One participant at the highest dose had a moderately severe reaction to IMC-I109V with symptoms of fever, difficulty breathing and low blood pressure. This is called cytokine release syndrome. It is caused by an overreaction of the immune system. It was treated quickly and resolved within a few hours. This was considered a serious side effect because the person stayed in the hospital a bit longer, but it did not meet the criteria for stopping the study. Five of the 20 participants (25%) experienced symptoms or changes in blood tests that were thought to be caused by IMC-I109V. These side effects included mild to moderate short-term symptoms, such as feverishness and tiredness, within a day after getting the drug. They occurred mainly in people in the higher dose groups. Three (15%) participants had temporary increases in a liver enzyme (ALT), which is a sign of liver inflammation, but these returned to normal or near-normal within two weeks. The side effects did not last long because IMC-I109V rapidly leaves the body. Everyone completed the study treatment and all the study visits. No deaths occurred during the study.
The researchers also monitored the levels of HBsAg in the blood. If the blood test does not detect this viral marker, it is a sign that the body has overcome the chronic hepatitis B infection, but this rarely happens with current treatments. After receiving IMC-I109V, 14 participants (70%) had lower levels of HBsAg in their blood, particularly those who received higher doses of the drug. In 4 participants, the drop in HBsAg was bigger than what the researchers had set as a meaningful change (a drop of at least 37%). For 3 of these 4 people, the lower HBsAg levels lasted until the end of the study, about a month later. There were also temporary increases in a marker of immune activity (a change in a chemical in blood called interleukin-6) at higher doses, which happened at the same time as the changes in liver enzyme and HBsAg.
Overall, the side effects and the changes in immune activity and HBsAg levels matched what was expected based on how the drug is designed to work.
No further studies of IMC-I109V are planned at the current time. However, findings from this study will be used to design next-generation drugs for hepatitis B that could lead to a ‘functional cure’, meaning that the body’s immune system keeps the virus under control without the need for lifelong treatment.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
20/YH/0276
Date of REC Opinion
16 Dec 2020
REC opinion
Further Information Favourable Opinion