Phase 1/2 study of IMC-I109V in non-cirrhotic HBeAg-negative chronic hepatitis B (HBV) infection
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
Immunocore Ltd
80 participants
May 18, 2021
Interventional
Conditions
Summary
Hepatitis B is the most common liver infection in the world and is caused by the hepatitis B virus (HBV). HBV enters the body and travels to the liver via the bloodstream. In the liver, the virus attaches to healthy liver cells and multiplies. The liver is the main site of HBV replication. Hepatitis B infection can lead to cirrhosis (scarring of the liver), liver cancer, or liver failure, if it is not diagnosed and managed appropriately. The purpose of this study is to test IMC-I109V in people with chronic hepatitis B virus (HBV) infection. The main goal of the study is to assess the safety and effectiveness a new treatment, called IMC-I109V. IMC- I109V has been developed to treat HBV by activating the body’s own immune system to fight the virus.
Eligibility
Inclusion Criteria17
- Aged 18 to 55 years inclusive, at the time of signing the informed consent.
- HLA-A*02:01 positive (central laboratory testing)
- Documented evidence of CHB based on one of the following:
- a. Positive HBsAg and HBV DNA at least 6 months prior to the screening visit; OR
- b. Historical liver biopsy consistent with CHB infection available.
- If previously HBeAg-positive, participants must be HBeAg-negative at the screening
- visit and have historical HBeAg-negative status greater than 3 months prior to the screening visit available for review.
- Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for
- greater than or equal to 12 months prior to screening and are willing to continue.
- HBV DNA negative at screening.
- Quantitative HBV surface antigen less than or equal to 1000 IU/mL at the screening visit. Participants with HBsAg levels greater than or equal to 1000 IU/mL and less than or equal to 3000 IU/mL may be eligible after consultation with, and approval by, the Sponsor’s Medical Monitor.
- All participants must have no history of liver cirrhosis AND prior assessment of fibrosis demonstrating non-cirrhotic status at screening. as defined by one of the following:
- a. Liver biopsy demonstrating a Metavir Fibrosis Score of F0-2 (or equivalent);
- OR
- b. Fibroscan® result of less than 9 kPa.
- Male and female participants of childbearing potential who are sexually active with a nonsterilized partner must agree to use highly effective methods of birth control from the trial screening date until 6 months after the final dose of the study intervention.
- Capable of giving signed informed consent.
Exclusion Criteria15
- Participants are excluded from the study if ANY of the following criteria apply:
- Known co-infection with any of the following:
- a. HIV
- b. Hepatitis C virus OR
- c. Hepatitis D virus
- Changes in HBeAg status within 3 months prior to the screening visit.
- Known HBV genotype A
- History of HCC
- Gilbert’s syndrome
- Any known pre-existing medical or psychiatric condition that could interfere with the participant’s ability to provide informed consent or participate in study conduct, or that may confound study findings.
- Significant immunosuppression from, but not limited to immunodeficiency conditions
- such as common variable hypogammaglobulinemia.
- Evidence of active or suspected malignancy, or a history of malignancy less than or equal to 3 years prior to the screening visit (except adequately treated carcinoma in situ and basal cell carcinoma of the skin).
- Known or suspected hypersensitivity or previous severe reactions to any of the constituents of IMC-I109V, or the drugs used in the pre-treatment regimen (eg, dexamethasone, ibuprofen and paracetamol).
- Pregnant or lactating women.
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Interventions
The purpose of this study is to test IMCI109V in people with chronic hepatitis B virus (HBV) infection and to assess the safety and effectiveness a new treatment, called IMC-I109V. IMC- I109V has been developed to treat HBV by activating the body’s own immune system to fight the virus. This is the first time that IMC-I109V is being tested in humans. The study consists of 2 parts as follows; Part 1 – Single Ascending Dose (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 (by intravenous (IV) infusion) and a 28 day follow-up period, for a total of 9 visits. The first cohort will receive a single IMC-I109V starting dose of 0.8 mcg, and subsequent cohorts up to 60.0 mcg. Visits will take place on Day -1 and Days 1, 2, 3, 5, 8, 15, 22, and 29. Follow up may be extended in participants who achieve a decrease in HBsAg of greater than 0.5 log10 IU/mL at Day 29. Approximately 5 to 9 cohorts will be enrolled. Part 2 – Multiple Ascending Dose (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 (by intravenous (IV) infusion), and a 24-week follow-up period, with a total of 30 visits. The initial dose in Part 2 – MAD will be the lowest dose evaluated during Part 1 – SAD i.e. 0.8 mcg. Visits will take place on Day -1 and Days 1, 3, 5, and 8, Weeks 3 (Day 15) through 24, Weeks 28, 36, 48 and 49. Participants who have achieved HBsAg less than 100 IU/mL at end of Week 24 may be considered for further study treatments of up to Week 48 and follow-up visits every 12 weeks to Week 72. Treatment will be discontinued at Week 16 in participants who have not shown evidence of a response to IMC-I109V. Approximately 3 to 6 dose cohorts will be enrolled and the maximum possible dose that may be administered to a cohort will be 60.0 mcg. The participant groups in SAD and MAD are exclusive.
Locations(11)
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ACTRN12620000403932