Phase 1/2 study of IMC-I109V in non-cirrhotic HBeAg-negative chronic HBV infectio

Phase 1

• Conditions: chronic hepatitis B virus (HBV) infection; MedDRA version: 20.0Level: LLTClassification code 10019182Term: HBVSystem Organ Class: 10022891 - Investigations; MedDRA version: 20.0Level: LLTClassification code 10019743Term: Hepatitis B virus (HBV)System Organ Class: 10022891 - Investigations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2019-004212-64-DK
• Lead Sponsor: Immunocore Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-30
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

1. Aged 18 to 65 years inclusive, at the time of signing the informed consent.
2. HLA-A*02:01 positive (central laboratory testing)
3. 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.
4. If previously HBeAg-positive, participants must be HBeAg-negative at the screening visit and have historical HBeAg-negative status >3 months prior to the screening visit available for review.
5. Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for = 12 months prior to screening and are willing to continue.
6. HBV DNA negative (below the LLOQ) at screening
7. Quantitative HBV surface antigen = 3000 IU/mL at the screening visit. Participants with HBsAg levels = 3000 IU/mL and = 5000 IU/mL may be eligible after consultation with, and approval by, the Sponsor’s Medical Monitor.
8. 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 < 9 kPa.
NOTE: A confirmatory Fibroscan® is required within 6 months prior to Day 1.
9. Liver imaging confirming absence of clinically significant abnormalities is required within 6 months prior to Day 1.
10. 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 3 months after the final dose of the study intervention or longer if required by local regulations; cessation of birth control after this point should be discussed with a responsible physician. *Male participants are not allowed to donate sperm from the time of enrollment until 3 months post-administration of study interventions or longer if required by local regulations.
*Female participants must refrain from egg donation during the course
of the study
11. Capable of giving signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 103
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Medical Conditions
1. Known co-infection with any of the following:
a. HIV
b. Hepatitis C virus OR
c. Hepatitis D virus
2. Changes in HBeAg status within 3 months prior to the screening visit
3. Known HBV genotype A
4. Gilbert's syndrome
5. 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
6. Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia
7. Evidence of active or suspected malignancy, or a history of malignancy = 3 years prior to the screening visit (except adequately treated carcinoma in situ, basal cell carcinoma of the skin, or stage 0 HCC that has been treated). NOTE: Participants under evaluation for malignancy are not eligible
8. Known or suspected hypersensitivity or previous severe reactions to any of the constituents of IMC-I109V, or the drugs used in the pretreatment
regimen (eg, dexamethasone, ibuprofen and paracetamol)
9. Pregnant or lactating women
Prior/Concomitant Therapy
10. Receiving or planning to receive systemic immunosuppressive medications during the study or = 2 months prior to Day 1, including but not limited to prednisone > 10 mg/day (or equivalent), methotrexate, cyclosporine, or interferon. NOTE: Local steroid therapy are allowed (eg, inhaled, otic, ophthalmic, or intra-articular medications).
Prior/Concurrent Clinical Study Experience
11. Use of any live vaccines against infectious diseases within 4 weeks of the first planned administration of study intervention or use of any non-live vaccines against infectious diseases within 2 weeks of the first planned administration of study intervention.
12. Treatment with any investigational drug or enrollment in any other clinical study = 6 months prior to Day 1, or at any time during participation in the study
Laboratory Exclusion Criteria
13. If any of the laboratory exclusion criteria are met, then the site may have the participant retested. If a single value is within ±10% of the listed laboratory exclusion criterion value upon retest, and the value is considered to be not clinically significant by the physician investigator, the participant may be considered for enrollment:
*ALT > 1.5 x ULN;
*AST > ULN;
*Total bilirubin and direct bilirubin > ULN;
*Albumin < 32 g/L;
*INR > 1.2;
*Hematologic, biochemical, and serologic criteria (transfusions or growth factors may not be used to achieve study entry requirements): Hemoglobin < 110 g/L for females and < 120 g/L for males, Neutrophils < 1.5 x 109/L (African descent: < 1.2 x 109/L); Platelets < 120 x 109/L
*Poorly controlled diabetes mellitus with whole blood hemoglobin A1c = 8.5%.
*Estimated glomerular filtration rate < 60 mL/min/1.73 m2
*AFP > 200 ng/mL. NOTE: For participants with alpha-fetoprotein results of 50 to 200 ng/mL, a liver ultrasound, computerized tomography scan, or magnetic resonance imaging scan is required to rule out malignancy. Participants with elevated AFP may be eligible, provided malignancy is ruled out and after consultation with, and approval by, the Sponsor’s Medical Monitor.
Other Exclusions
14. Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine = 12 months prior to the screening visit, except for those participants monitored in an opioid substitution maintenance program
15. Poor venous access that precludes routine peripheral bloo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified