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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05867056




Registration number
NCT05867056
Ethics application status
Date submitted
12/04/2023
Date registered
19/05/2023
Date last updated
19/03/2024

Titles & IDs
Public title
Study of IMC-I109V in Non-cirrhotic HBeAg-negative Chronic HBV Infection
Scientific 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
Secondary ID [1] 0 0
2019-004212-64
Secondary ID [2] 0 0
IMC-I109V-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IMC-I109V Single Ascending Dose
Treatment: Drugs - IMC-I109V Multiple Ascending Doses
Treatment: Drugs - HBV HCC Module MAD

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.

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 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.

Experimental: Part 3: HBV HCC Module MAD - 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.


Treatment: Drugs: IMC-I109V Single Ascending Dose
Single dose administration of IMC-I109V

Treatment: Drugs: IMC-I109V Multiple Ascending Doses
Multidose administration of IMC-I109V

Treatment: Drugs: HBV HCC Module MAD
Multidose administration of IMC-I109V
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts 1, 2, and 3: Incidence and treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [2] 0 0
Parts 1, 2, and 3: Incidence of serious adverse events (SAEs)
Timepoint [2] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [3] 0 0
Parts 1, 2, and 3: Incidence of adverse events (AEs) leading to treatment discontinuation
Timepoint [3] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [4] 0 0
Parts 1, 2, and 3: Incidence of dose-limiting toxicities (DLTs)
Timepoint [4] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [5] 0 0
Parts 1, 2, and 3: Changes in Vital Signs
Timepoint [5] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [6] 0 0
Parts 1, 2, and 3: Changes in electrocardiogram
Timepoint [6] 0 0
Up to 30 days after the last infusion of study treatment
Primary outcome [7] 0 0
Parts 1, 2, and 3: Change in safety laboratory parameters
Timepoint [7] 0 0
Up to 30 days after the last infusion of study treatment
Secondary outcome [1] 0 0
Parts 1, 2, and 3: Maximum drug concentration (Cmax)
Timepoint [1] 0 0
At designated timepoints up to 162 days post-dose
Secondary outcome [2] 0 0
Parts 1, 2, and 3: Area under the plasma concentration versus time curve (AUC)
Timepoint [2] 0 0
At designated timepoints up to 162 days post-dose
Secondary outcome [3] 0 0
Parts 1, 2, and 3: The time to reach maximum drug concentration (Tmax)
Timepoint [3] 0 0
At designated timepoints up to 162 days post-dose
Secondary outcome [4] 0 0
Parts 1, 2, and 3: The elimination half-life (t1/2)
Timepoint [4] 0 0
At designated timepoints up to 162 days post-dose
Secondary outcome [5] 0 0
Parts 1, 2, and 3: Incidence of anti-IMC-109V antibody formations
Timepoint [5] 0 0
At designated timepoints up to 162 days post-dose
Secondary outcome [6] 0 0
Parts 1, 2, and 3: Antiviral Effects: HBsAg change from baseline
Timepoint [6] 0 0
Up to 280 days post-dose
Secondary outcome [7] 0 0
Parts 1, 2, and 3: Antiviral Effects: HBcrAg change from baseline
Timepoint [7] 0 0
Up to 280 days post-dose
Secondary outcome [8] 0 0
Parts 1, 2, and 3: Antiviral Effects: HBV RNA change from baseline
Timepoint [8] 0 0
Up to 280 days post-dose
Secondary outcome [9] 0 0
Parts 1, 2, and 3: Antiviral Effects: HBsAb change from baseline
Timepoint [9] 0 0
Up to 280 days post-dose
Secondary outcome [10] 0 0
Part 3 only: Objective response rate (ORR) as determined by RECIST v1.1 as assessed by the Investigator
Timepoint [10] 0 0
Up to ~52 months
Secondary outcome [11] 0 0
Part 3 only: Overall survival (OS) as determined by RECIST v1.1 as assessed by the Investigator
Timepoint [11] 0 0
Up to ~52 months
Secondary outcome [12] 0 0
Part 3 only: Progression-free survival (PFS) as determined by RECIST v1.1 as assessed by the Investigator
Timepoint [12] 0 0
Up to ~52 months
Secondary outcome [13] 0 0
Part 3 only: Duration of response (DOR) as determined by RECIST v1.1 as assessed by the Investigator
Timepoint [13] 0 0
Up to ~52 months

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/12/2024
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [2] 0 0
The Alfred Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
VIC 3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
Denmark
State/province [3] 0 0
Aarhus
Country [4] 0 0
Hong Kong
State/province [4] 0 0
Hong Kong
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Busan
Country [6] 0 0
Romania
State/province [6] 0 0
Bucharest
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Madrid
Country [9] 0 0
Taiwan
State/province [9] 0 0
Kaohsiung City
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taipei city
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Immunocore Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Immunocore Medical Information
Address 0 0
Country 0 0
Phone 0 0
844-466-8661
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/ct2/show/NCT05867056