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

Sponsor

Immunocore Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05867056

Collaborator

(none)

108

Enrollment

Locations

Arms

52.1

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: IMC-I109V-101 Single Ascending Dose Drug: IMC-I109V-101 Multiple Ascending Doses	Phase 1

Detailed Description

IMC-I109V-101 is a first-in-human (FIH) study designed to assess the safety, tolerability, and pharmacokinetic (PK) profile of IMC-I109V in single and multiple dose regimens and to provide a preliminary assessment of antiviral activity, when administered to virally suppressed hepatitis B e-antigen (HBeAg)-negative participants receiving long-term NA therapy. The aim of this study is to identify safe, tolerable, and clinically active dose (CAD) regimens of IMC-I109V for further clinical development. The IMC-I109V study is divided into 2 main parts: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Participants will receive a single dose of IMC-I109V-101 in Part 1 (SAD) and 24 weekly doses in Part 2 (MAD).Participants will receive a single dose of IMC-I109V-101 in Part 1 (SAD) and 24 weekly doses in Part 2 (MAD).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Study Evaluating the Safety, Antiviral Activity, and Pharmacokinetics of IMC-I109V in HLA-A*02:01 Positive Participants With Chronic HBV Infection Who Are Non-Cirrhotic, Hepatitis B e Antigen-negative, and Virally Suppressed

Actual Study Start Date :

Aug 12, 2020

Anticipated Primary Completion Date :

Sep 10, 2024

Anticipated Study Completion Date :

Dec 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Single Ascending Dose (SAD) 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-101 Single Ascending Dose Single dose administration of IMC-I109V-101 Other Names: SAD
Experimental: Part 2: Multiple Ascending Doses (MAD) 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 29visits. 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/mLat 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-101 Multiple Ascending Doses Multidose administration of IMC-I109V-101 Other Names: MAD

Arm

Intervention/Treatment

Experimental: Part 1: Single Ascending Dose (SAD)

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-101 Single Ascending Dose

Single dose administration of IMC-I109V-101

Other Names:

SAD

Experimental: Part 2: Multiple Ascending Doses (MAD)

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 29visits. 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/mLat 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-101 Multiple Ascending Doses

Multidose administration of IMC-I109V-101

Other Names:

MAD

Outcome Measures

Primary Outcome Measures

Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 280 days post-dose]
Incidence of serious adverse events (SAEs) [Up to 280 days post-dose]
Incidence of adverse events (AEs) leading to treatment discontinuation [Up to 280 days post-dose]
Incidence of dose-limiting toxicities (DLTs) [Up to 280 days post-dose]
Changes in Vital Signs [Up to 280 days post-dose]
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.
Changes in electrocardiogram [Up to 280 days post-dose]
QTcF interval absolute values and changes from baseline.
Change in safety laboratory parameters [Up to 280 days post-dose]
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.

Secondary Outcome Measures

Maximum drug concentration (Cmax) [Up to 162 days post-dose]
Area under the plasma concentration versus time curve (AUC) [Up to 280 days post-dose]
The time to reach maximum drug concentration (Tmax) [Up to 280 days post-dose]
The elimination half-life (t1/2) [Up to 280 days post-dose]
Incidence of anti-IMC-109V antibody formations [Up to 280 days post-dose]
Antiviral Effects: HBsAg change from baseline [Up to 280 days post-dose]
Antiviral Effects: HBcrAg change from baseline [Up to 280 days post-dose]
Antiviral Effects: HBV RNA change from baseline [Up to 280 days post-dose]
Antiviral Effects: HBsAb change from baseline [Up to 280 days post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California Keck School of Medicine	Los Angeles	California	United States	90033
2	New York Presbyterian Hospital Cornell University Joan & Sanford I. Weill Medical College	New York	New York	United States	10021
3	University Hospitals Cleveland Medical Center Case Western Reserve	Cleveland	Ohio	United States	44106
4	Linear Clinical Research	Crawley		Australia	6009
5	St. Vincent's Hospital	Fitzroy		Australia	3065
6	Scienta Clinical Research	Randwick		Australia	2031
7	Universitair Ziekenhuis Antwerp	Antwerpen		Belgium	2060
8	Queen Mary Hospital	Hong Kong		Hong Kong
9	Pusan National University Hospital	Busan		Korea, Republic of	49241
10	Asan Medical Center	Seoul		Korea, Republic of	05505
11	Gangnam Severance Hospital-Yonsei University Health System	Seoul		Korea, Republic of	06273
12	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
13	Auckland Clinical Studies	Grafton		New Zealand	1010
14	ID Clinic Myslowice	Mysłowice		Poland	41-400
15	ARENSIA Exploratory Medicine Research Clinic	Bucharest		Romania	010458
16	Hospital Universitari Vall d'Hebron de Barcelona	Barcelona		Spain	08035
17	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda		Spain	28222
18	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29071
19	Chelsea and Westminster Hospital, Research and Development, Clinical Trials Facility	London		United Kingdom	SW10 9NH
20	Nottingham University Hospitals NHS Trust Biomedical Research Centre	Nottingham		United Kingdom	NG7 2UH