Study of IMC-I109V in Non-cirrhotic HBeAg-negative Chronic HBV Infection

NCT05867056 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: IMC-I109V-1012019-004212-64
• Study Type: interventional
• Target: N/A
• Locations: 9 countries
• Sites: 15

Brief Summary

IMC-I109V is an immune-mobilizing monoclonal T cell receptor (TCR) against viruses (ImmTAV®), a new class of bispecific protein therapeutics designed for the treatment of chronic hepatitis B virus (HBV) infection (CHB). This is the first in-human study of IMC-I109V in persons with CHB.

Conditions

Hepatitis B, Chronic

Keywords

HBeAg negative; HLA-A*02;01 Positive; T Cell Receptor (TCR)

Outcome Measures

Primary Outcomes (7)

• Parts 1, 2, and 3: Incidence and treatment-emergent adverse events (TEAEs)

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Incidence of serious adverse events (SAEs)

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Incidence of adverse events (AEs) leading to treatment discontinuation

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Incidence of dose-limiting toxicities (DLTs)

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Changes in Vital Signs

  Number of participants with, and rate of, Grade 1, Grade 2, Grade 3, and Grade 4 (as applicable per NCI CTCAE v5.0) vital sign abnormalities.

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Changes in electrocardiogram

  QTcF interval absolute values and changes from baseline.

  Up to 30 days after the last infusion of study treatment

• Parts 1, 2, and 3: Change in safety laboratory parameters

  Number of participants with, and rate of, Grade 1, Grade 2, Grade 3, and Grade 4 (as applicable per NCI CTCAE v5.0) laboratory abnormalities.

  Up to 30 days after the last infusion of study treatment

Secondary Outcomes (13)

• Parts 1, 2, and 3: Maximum drug concentration (Cmax)

  At designated timepoints up to 162 days post-dose

• Parts 1, 2, and 3: Area under the plasma concentration versus time curve (AUC)

  At designated timepoints up to 162 days post-dose

• Parts 1, 2, and 3: The time to reach maximum drug concentration (Tmax)

  At designated timepoints up to 162 days post-dose

• Parts 1, 2, and 3: The elimination half-life (t1/2)

  At designated timepoints up to 162 days post-dose

• Parts 1, 2, and 3: Incidence of anti-IMC-109V antibody formations

  At designated timepoints up to 162 days post-dose

Study Arms (3)

Part 1: Single Ascending Dose (SAD)

EXPERIMENTAL

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 8 visits. Visits will take place on Day -1 and Days 1, 2, 3, 8, 15, 22, and 29. Follow-up may be extended in participants who achieve a decrease in HBsAg of \> 0.5 log10 IU/mL at Day 29.

Drug: IMC-I109V Single Ascending Dose

Part 2: Multiple Ascending Doses (MAD)

EXPERIMENTAL

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 29 visits. Visits will take place on Day -1 and Days 1, 3 and 8, Weeks 3 (Day 15) through 24, Weeks 28, 36, 48 and 49. Participants who have achieved HBsAg \<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, in order to minimize unnecessary drug exposure in participants who are unlikely to achieve reductions in viral biomarkers with further doses.

Drug: IMC-I109V Multiple Ascending Doses

Part 3: HBV HCC Module MAD

EXPERIMENTAL

Enrollment into Part 3 may begin at the discretion of the Sponsor and will involve a maximum 42-day screening period, a treatment period comprising weekly administration of the target dose until the criteria for treatment discontinuation are met. Visits will take place on Day 1-2 and Day 8, Week 3 (Day 15), with this cycle being repeated until treatment stops, then 30 and 90 days post-last dose, then every 3 months after last dose, after which there will be a safety follow-up period of 30 days.

Drug: HBV HCC Module MAD

Interventions

IMC-I109V Single Ascending Dose DRUG

Single dose administration of IMC-I109V

Also known as: SAD

Part 1: Single Ascending Dose (SAD)

IMC-I109V Multiple Ascending Doses DRUG

Multidose administration of IMC-I109V

Also known as: MAD

Part 2: Multiple Ascending Doses (MAD)

HBV HCC Module MAD DRUG

Multidose administration of IMC-I109V

Part 3: HBV HCC Module MAD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts 1 and 2:
• ≥18 to 65 years old at time of informed consent
• HLA-A\*02:01 positive
• 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.
• Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for ≥12months prior to screening and are willing to continue.
• HBV DNA negative at screening
• No history of liver cirrhosis AND prior assessment of fibrosis demonstrating non-cirrhotic status at screening
• Participants of childbearing potential who are sexually active with a non-sterilized 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
• Part 3:
• ≥18 years old at time of informed consent
• HLA-A\*02:01 positive
• ECOG ≤1
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology / cytology, or clinically by American Association for the Study of Liver Diseases criteria
• Failed or intolerant of ≥1 systemic therapy
• At least one measurable lesion (per RECIST 1.1) which is either not previously treated or, if treated, has clearly progressed prior to enrollment

You may not qualify if:

• Parts 1 and 2:
• Pregnant or lactating persons
• Known co-infection with any of the following: HIV, Hepatitis C virus, OR Hepatitis D virus
• Changes in HBeAg status within 3 months prior to the screening visit
• Known HBV genotype A
• 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 including, but not limited to: Immunologically-mediated disease, e.g. inflammatory bowel disease (Crohn's disease, ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, scleroderma, or sarcoidosis within 5 years of the screening visit.
• Current or history of any clinically significant cardiac abnormalities/dysfunction, e.g. congestive heart failure, myocardial infarction ≤6 months prior to the screening visit, pulmonary hypertension, complex congenital heart disease, significant arrhythmia, or active cardiac ischemia.
• Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, or hepatic encephalopathy.
• 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 ≤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
• Receiving or planning to receive systemic immunosuppressive medications during the study or ≤ 2 months prior to Day1, including but not limited to prednisone \>10 mg/day (or equivalent), methotrexate, cyclosporine, or interferon. NOTE: Local steroid therapy is allowed (eg, inhaled, otic, ophthalmic, or intra-articular medications)
• 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.
• Treatment with any investigational drug or enrollment in any other clinical study ≤ 3 months prior to Day1, or at any time during participation in the study.
• 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.

Sponsors & Collaborators

• Immunocore Ltd: lead

Study Sites (15)

University of Southern California Keck School of Medicine

Los Angeles, California, 90033, United States

Location

University Hospitals Cleveland Medical Center Case Western Reserve

Cleveland, Ohio, 44106, United States

Location

St. Vincent's Hospital

Fitzroy, 3065, Australia

Location

The Alfred Centre

Melbourne, VIC 3004, Australia

Location

Aarhus University

Aarhus, 8200, Denmark

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

ARENSIA Exploratory Medicine Research Clinic

Bucharest, 010458, Romania

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Hospital Universitari Vall d'Hebron de Barcelona

Barcelona, 08035, Spain

Location

Hospital Ramón and Cajal

Madrid, 28034, Spain

Location

Kaohsiung Medical University Chung-Ho

Kaohsiung City, 80756, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Guy's Hospital, Dept. of Infectious Disease

London, SE1 9RT, United Kingdom

Location

Chelsea and Westminster Hospital, Research and Development, Clinical Trials Facility

London, SW10 9NH, United Kingdom

Location

Nottingham University Hospitals NHS Trust Biomedical Research Centre

Nottingham, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive a single dose of IMC-I109V-101 in Part 1 (SAD) and 24 weekly doses in Part 2 (MAD). Participants in Part 3 will receive weekly doses of IMC-I109V until disease progression, unacceptable toxicity, or other reason for treatment discontinuation occurs.

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 19, 2023
• Study Start: August 12, 2020
• Primary Completion: September 10, 2024
• Study Completion: December 15, 2024
• Last Updated: October 15, 2024

Record last verified: 2024-10

Locations

DK (1); GB (3); RO (1); HK (1); KR (1); AU (2); ES (2); US (2); TW (2)