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Hepatitis B, ChronicPhase 1NCT05867056

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

A Phase 1 study testing IMC-I109V Single Ascending Dose, IMC-I109V Multiple Ascending Doses and HBV HCC Module MAD in people with Hepatitis B, Chronic, run by Immunocore Ltd at 15 sites in 9 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Hepatitis B, Chronic
What is being tested?
IMC-I109V Single Ascending Dose, IMC-I109V Multiple Ascending Doses and HBV HCC Module MAD
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
15 sitesin 9 countries
Study dates
12 Aug 2020to 15 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

15 sites in 9 countries.

15 sites in 9 countries

United Kingdom3 sites
  • Guy's Hospital, Dept. of Infectious Disease

    London, SE1 9RT

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

    London, SW10 9NH

  • Nottingham University Hospitals NHS Trust Biomedical Research Centre

    Nottingham, NG7 2UH

Other trials in United Kingdom

United States2 sites
  • University Hospitals Cleveland Medical Center Case Western Reserve

    Cleveland, Ohio, 44106

  • University of Southern California Keck School of Medicine

    Los Angeles, California, 90033

Other trials in United States

Australia2 sites
  • St. Vincent's Hospital

    Fitzroy, 3065

  • The Alfred Centre

    Melbourne, VIC 3004

Other trials in Australia

Spain2 sites
  • Hospital Universitari Vall d'Hebron de Barcelona

    Barcelona, 08035

  • Hospital Ramón and Cajal

    Madrid, 28034

Other trials in Spain

Taiwan2 sites
  • Kaohsiung Medical University Chung-Ho

    Kaohsiung City, 80756

  • Taipei Veterans General Hospital

    Taipei, 112

Other trials in Taiwan

Denmark1 site
  • Aarhus University

    Aarhus, 8200

Other trials in Denmark

Hong Kong1 site
  • Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

Romania1 site
  • ARENSIA Exploratory Medicine Research Clinic

    Bucharest, 010458

Other trials in Romania

South Korea1 site
  • Pusan National University Hospital

    Busan, 49241

Other trials in South Korea

About this study

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

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.

Read the 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 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.

Being tested
IMC-I109V Single Ascending Dose, IMC-I109V Multiple Ascending Doses, HBV HCC Module MAD
Keywords
HBeAg negative, HLA-A*02;01 Positive, T Cell Receptor (TCR)
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMC-I109V Single Ascending DoseDrug

    Also called SAD

    Single dose administration of IMC-I109V

  • IMC-I109V Multiple Ascending DosesDrug

    Also called MAD

    Multidose administration of IMC-I109V

  • HBV HCC Module MADDrug

    Multidose administration of IMC-I109V

Study groups in NCT05867056
Study groupRoleWhat they receive
Part 1: Single Ascending Dose (SAD)ExperimentalSAD 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.
Receives: Drug: IMC-I109V Single Ascending Dose
Part 2: Multiple Ascending Doses (MAD)ExperimentalMAD 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.
Receives: Drug: IMC-I109V Multiple Ascending Doses
Part 3: HBV HCC Module MADExperimentalEnrollment 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.
Receives: Drug: HBV HCC Module MAD

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 30 days after the last infusion of study treatment

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

    Measured: Up to 30 days after the last infusion of study treatment

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

    Measured: Up to 30 days after the last infusion of study treatment

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

    Measured: Up to 30 days after the last infusion of study treatment

  5. 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.

    Measured: Up to 30 days after the last infusion of study treatment

  6. Parts 1, 2, and 3: Changes in electrocardiogram

    QTcF interval absolute values and changes from baseline.

    Measured: Up to 30 days after the last infusion of study treatment

  7. 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.

    Measured: Up to 30 days after the last infusion of study treatment

Secondary outcomes (13)
  1. Parts 1, 2, and 3: Maximum drug concentration (Cmax)

    Measured: At designated timepoints up to 162 days post-dose

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

    Measured: At designated timepoints up to 162 days post-dose

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

    Measured: At designated timepoints up to 162 days post-dose

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

    Measured: At designated timepoints up to 162 days post-dose

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

    Measured: At designated timepoints up to 162 days post-dose

  6. Parts 1, 2, and 3: Antiviral Effects: HBsAg change from baseline

    Measured: Up to 280 days post-dose

  7. Parts 1, 2, and 3: Antiviral Effects: HBcrAg change from baseline

    Measured: Up to 280 days post-dose

  8. Parts 1, 2, and 3: Antiviral Effects: HBV RNA change from baseline

    Measured: Up to 280 days post-dose

  9. Parts 1, 2, and 3: Antiviral Effects: HBsAb change from baseline

    Measured: Up to 280 days post-dose

  10. Part 3 only: Objective response rate (ORR) as determined by RECIST v1.1 as assessed by the Investigator

    Measured: Up to ~52 months

  11. Part 3 only: Overall survival (OS) as determined by RECIST v1.1 as assessed by the Investigator

    Measured: Up to ~52 months

  12. Part 3 only: Progression-free survival (PFS) as determined by RECIST v1.1 as assessed by the Investigator

    Measured: Up to ~52 months

  13. Part 3 only: Duration of response (DOR) as determined by RECIST v1.1 as assessed by the Investigator

    Measured: Up to ~52 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2023
  2. Study start12 Aug 2020
  3. Primary completion10 Sep 2024 (estimated)
  4. Study completion15 Dec 2024 (estimated)

Why it stopped: Enrollment into the phase 2 portion was never initiated.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
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 in Part 3 will receive weekly doses of IMC-I109V until disease progression, unacceptable toxicity, or other reason for treatment discontinuation occurs.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05867056
Sponsor's protocol ID
IMC-I109V-101
Other IDs
2019-004212-64, 2019
Status last verified
Oct 2024
First submitted
12 Apr 2023
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IMC-I109V Single Ascending Dose, IMC-I109V Multiple Ascending Doses and HBV HCC Module MAD in people with Hepatitis B, Chronic, run by Immunocore Ltd at 15 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United Kingdom, United States, Australia, Spain, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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