Study of IMC-I109V in Non-cirrhotic HBeAg-negative Chroni... | NCT05867056

ID	Type	Description	Link
2019-004212-64	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Name	Type	Description	Arm Group Labels	Other Names
IMC-I109V Single Ascending Dose	Drug	Single dose administration of IMC-I109V	Part 1: Single Ascending Dose (SAD)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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

Eligibility Module

Eligibility Criteria

Inclusion Criteria

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
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
Life expectancy >3 months from time of enrolment
Have compensated cirrhosis with a Child-Pugh score ≤ 7 (A or B7)
On entecavir and/or tenofovir (disoproxil fumarate or alafenamide) with HBV DNA <100IU/ml at screening; willingness to continue for at least 6 months after the last dose of study drug
Quantitative HBV surface antigen ≤ 5,000 IU/mL 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:

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.

Part 3:

Pregnant or lactating persons
Untreated or symptomatic CNS metastases
Significant ongoing toxicity from prior anticancer treatment -
Ascites requiring recurrent paracentesis
Inadequate washout from prior anticancer therapy
Prior cellular therapy for HBV-associated HCC
Known HBV genotype A
Decompensated liver disease
Surgical intervention or local / loco-regional therapy for HBV HCC within 28 days of planned first dose of study treatment
Active hepatitis C virus (HCV) infection
Untreated HIV infection
Significant secondary malignancy
Clinically significant lung, heart, or autoimmune disease
Ongoing requirement for immunosuppressive treatment
Prior solid organ or bone marrow transplant
Hypersensitivity to study drug or excipients, or pre-medications
Systemic antibiotics, vaccines or major surgery within 2-4 weeks prior to the first dose of study intervention
Out-of-range laboratory values, including ALT or AST > 3x upper limit of normal (ULN), total bilirubin and direct bilirubin > 1.5x ULN, Albumin ≤ 28 g/L, International normalized ratio (INR) > 1.3

ID	Term
D006509	Hepatitis B
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms