chronic hepatitis B virus (HBV) infection MedDRA version: 20.0 Level: LLT Classification code 10019182 Term: HBV System Organ Class: 100000004848 MedDRA version: 20.0 Level: LLT Classification code 10019743 Term: Hepatitis B virus (HBV) System Organ Class: 100000004848
Conditions
Sponsors
Immunocore Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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 1.2; *Hematologic, biochemical, and serologic criteria (transfusions or growth factors may not be used to achieve study entry requirements): Hemoglobin 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 pre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary (Part 1 – SAD) To evaluate the safety and tolerability of IMC-I109V when administered as a single dose in virally suppressed, HBeAg-negative participants Primary (Part 2 – MAD) To evaluate the safety and tolerability of IMC-I109V when administered in a multiple dose schedule up to Week 24 in virally suppressed, HBeAg-negative participants;Secondary Objective: 1) To characterize the PK profile of IMC-I109V in single dose and multiple dose schedules 2) To evaluate incidence of anti-IMC-I109V antibody formations following single and multiple infusions 3) To assess the antiviral effects of IMC-I109V following administration of SAD and MAD schedules using HBV biomarkers;Primary end point(s): • Incidence and severity of treatment-emergent adverse events (TEAEs) • Incidence of dose-limiting toxicities (DLTs) • Changes in safety laboratory parameters, vital signs, and electrocardiogram (QTcF), • Incidence of serious adverse events (SAEs) • Incidence of adverse events (AEs) leading to treatment discontinuation Through 28 days after the last infusion of study treatment;Timepoint(s) of evaluation of this end point: Through 28 days after the last infusion of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): IMC-I109V serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses Incidence of anti-IMC-I109V antibody formation following administration of 1 or more doses of study drug HBsAg, hepatitis core-related antigen (HBcrAg), HBV RNA, HBsAb changes from baseline through end of trial;Timepoint(s) of evaluation of this end point: -IMC-I109V serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses - Incidence of anti-IMC-I109V antibody formation following administration of 1 or more doses of study drug SAD – W1D1 and W4D1 MAD - pre-dose (dose 1, dose 3, dose 5, dose 16 and EOT (last dose) and Follow-up Week 24 (last FU week) - HBsAg, hepatitis B core-related antigen (HBcrAg), HBV RNA, HBsAb changes from baseline through end of trial SAD – W1D1, W1D3, W2D1, W3D1, W4D1, W5D1 MAD - performed weekly Week 1-Week 8, then every 4 weeks during Week 8-Week 24 | — |
Countries
Australia, Belgium, Denmark, Hong Kong, Korea, Republic of, New Zealand, Poland, Romania, Spain, Ukraine, United Kingdom
Contacts
Public ContactSheetal Thakur
Immunocore Ltd
Outcome results
None listed