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.
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 3 main parts: Part 1 - Single Ascending Dose (SAD); Part 2 - Multiple Ascending Dose (MAD), in HBeAg-negative CHB; Part 3 will evaluate safety, tolerability, antiviral activity, PK and anti-tumor efficacy of Multiple Ascending Doses of IMC-I109V in participants with HBV-associated hepatocellular carcinoma (HBV HCC) who are virally suppressed on NA therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Single dose administration of IMC-I109V
Multidose administration of IMC-I109V
Multidose administration of IMC-I109V
University of Southern California Keck School of Medicine
Los Angeles, California, United States
University Hospitals Cleveland Medical Center Case Western Reserve
Cleveland, Ohio, United States
Parts 1, 2, and 3: Incidence and treatment-emergent adverse events (TEAEs)
Time frame: Up to 30 days after the last infusion of study treatment
Parts 1, 2, and 3: Incidence of serious adverse events (SAEs)
Time frame: 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
Time frame: Up to 30 days after the last infusion of study treatment
Parts 1, 2, and 3: Incidence of dose-limiting toxicities (DLTs)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 30 days after the last infusion of study treatment
Parts 1, 2, and 3: Maximum drug concentration (Cmax)
Time frame: At designated timepoints up to 162 days post-dose
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St. Vincent's Hospital
Fitzroy, Australia
The Alfred Centre
Melbourne, Australia
Aarhus University
Aarhus, Denmark
Queen Mary Hospital
Hong Kong, Hong Kong
ARENSIA Exploratory Medicine Research Clinic
Bucharest, Romania
Pusan National University Hospital
Busan, South Korea
Hospital Universitari Vall d'Hebron de Barcelona
Barcelona, Spain
Hospital Ramón and Cajal
Madrid, Spain
...and 5 more locations
Parts 1, 2, and 3: Area under the plasma concentration versus time curve (AUC)
Time frame: At designated timepoints up to 162 days post-dose
Parts 1, 2, and 3: The time to reach maximum drug concentration (Tmax)
Time frame: At designated timepoints up to 162 days post-dose
Parts 1, 2, and 3: The elimination half-life (t1/2)
Time frame: At designated timepoints up to 162 days post-dose
Parts 1, 2, and 3: Incidence of anti-IMC-109V antibody formations
Time frame: At designated timepoints up to 162 days post-dose
Parts 1, 2, and 3: Antiviral Effects: HBsAg change from baseline
Time frame: Up to 280 days post-dose
Parts 1, 2, and 3: Antiviral Effects: HBcrAg change from baseline
Time frame: Up to 280 days post-dose
Parts 1, 2, and 3: Antiviral Effects: HBV RNA change from baseline
Time frame: Up to 280 days post-dose
Parts 1, 2, and 3: Antiviral Effects: HBsAb change from baseline
Time frame: Up to 280 days post-dose
Part 3 only: Objective response rate (ORR) as determined by RECIST v1.1 as assessed by the Investigator
Time frame: Up to ~52 months
Part 3 only: Overall survival (OS) as determined by RECIST v1.1 as assessed by the Investigator
Time frame: Up to ~52 months
Part 3 only: Progression-free survival (PFS) as determined by RECIST v1.1 as assessed by the Investigator
Time frame: Up to ~52 months
Part 3 only: Duration of response (DOR) as determined by RECIST v1.1 as assessed by the Investigator
Time frame: Up to ~52 months