Safety and Immunotherapeutic Activity of Cemiplimab in Participants With HBV on Suppressive Antiviral Therapy

NCT04046107 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: ACTG A536838410
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 8

Brief Summary

The purpose of this study is to evaluate the safety and immunotherapeutic activity of cemiplimab in participants with hepatitis B virus (HBV) on suppressive antiviral therapy.

Conditions

Hepatitis B Virus

Keywords

Hepatitis B; Chronic hepatitis B; Functional cure; Immunotherapy; Checkpoint inhibitor therapy

Outcome Measures

Primary Outcomes (3)

• Number of participants who experienced any targeted safety event that is related to study treatment

  Targeted safety events include: * Hepatic encephalopathy * Ascites * Grade 2 or higher ALT elevation with INR greater than 1.5 or direct bilirubin greater than 1.5, unless occurring as part of HBeAg or HBsAg seroconversion to anti-HBe or anti-HBs or greater than 1 log decline in quantitative HBsAg with ALT resolution to Grade 1 or less within 60 days of elevation. * Non-hepatic AE of Grade 3 or higher * Adrenal insufficiency or adrenal crisis, confirmed, Grades 1-3 * Myocarditis, Grades 1-3 * Pneumonitis, Grades 2-3 * Infusion-related reaction, Grade 3 * Rash, Grade 3 * Uveitis, Grades 1-3 * Immune mediated hyper- or hypothyroidism, Grades 2-3 * Colitis, Grade 3 or higher * Myositis, Grades 2-3 * Immune-mediated hepatitis * Death DAIDS AE Grading Table (V2.1) is used.

  From Week 6 to Week 18

• Number of participants who discontinue treatment and/or study which is related to any adverse event

  Attributed to any adverse event as reported by the site

  From Week 6 to Week 18

• Number of participants with any AE

  Study protocol requires reporting of all targeted events (listed in Primary Outcome Measure 1 above), all Grade 1 or higher AEs, and any AE that occurs during the infusion or within 24 hours after infusion. DAIDS AE Grading Table (V2.1) is used.

  From entry to Week 90

Secondary Outcomes (6)

• Change in quantitative HBsAg from pre-treatment

  Entry and Weeks 6, 8, 12, 14, 18, 24, 36, 54, 72, 90

• Number of participants with detectable HBsAg

  Entry and Weeks 6, 12, 18, 36, 54, 72, Week 90

• Number of participants with anti-HBs conversion from negative (at study Week 6) to positive at a subsequent visit

  Weeks 6, 12, 18, 36, 54, 72, 90

• Number of participants with anti-HBe conversion from negative (at study Week 6) to positive at a subsequent visit

  Entry and Weeks 6, 12, 18, 36, 54, 72, 90

• Change in quantitative HBeAg from pre-treatment

  Entry and Weeks 6, 12, 18, 36, 54, 72, 90

Study Arms (3)

Cohort 1: Cemiplimab (0.3 mg/kg)

EXPERIMENTAL

Participants will receive cemiplimab 0.3 mg/kg dosed in two infusions, one infusion at Week 6 and Week 12.

Biological: Cemiplimab

Cohort 2: Cemiplimab (1 mg/kg)

EXPERIMENTAL

Participants will receive cemiplimab 1 mg/kg dosed in two infusions, one infusion at Week 6 and Week 12.

Biological: Cemiplimab

Cohort 3: Cemiplimab (3 mg/kg)

EXPERIMENTAL

Participants will receive cemiplimab 3 mg/kg dosed in two infusions, one infusion at Week 6 and Week 12.

Biological: Cemiplimab

Interventions

Cemiplimab BIOLOGICAL

Administered as an intravenous (IV) infusion

Also known as: REGN2810

Cohort 1: Cemiplimab (0.3 mg/kg); Cohort 2: Cemiplimab (1 mg/kg); Cohort 3: Cemiplimab (3 mg/kg)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic HBV infection (defined as hepatitis B surface antigen \[HBsAg\] positive).
• Receiving treatment at the time of study entry and for ≥12 months prior to study entry with HBV-active nucleos(t)ides, with tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), TDF/emtricitabine (FTC), TAF/FTC, or entecavir.
• Ability and willingness of participant to provide informed consent.
• Ability and willingness of participant to continue HBV antiviral therapy throughout the study.
• Weight ≥40 kg and \<200 kg.
• Evidence of limited or no evidence of fibrosis (F0-F2) by liver biopsy or non-invasive alternative, as defined in the study protocol.
• The following laboratory values obtained within 60 days prior to study entry:
• HBV DNA level \<20 IU/mL
• Documentation of hepatitis B e antigen (HBeAg) status (positive or negative)
• Hemoglobin ≥14.0 g/dL for male, ≥12.0 g/dL for female participants
• Platelets ≥150,000/mm\^3
• Absolute neutrophil count (ANC) \>1500/mm\^3
• International normalized ratio (INR) ≤1.1
• Albumin ≥3.5 g/dL
• Creatinine Clearance ≥60 mL/min, as calculated by the Cockcroft-Gault equation

You may not qualify if:

• Any malignancy within the 5 years prior to study entry or current malignancy requiring cytotoxic therapy.
• Current chronic, acute, or recurrent bacterial, fungal, or viral (other than HBV) infections that are serious, in the opinion of the site investigator, and that required systemic therapy within 30 days prior to study entry.
• Prior history of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, hypophysitis, multiple sclerosis, or sarcoidosis.
• NOTE: For questions related to the definition of autoimmune disorders, sites should contact the team per the study protocol.
• Any known acquired or congenital immune deficiency.
• History of chronic obstructive pulmonary disease (COPD).
• History of significant pulmonary conditions.
• Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring:
• Daily steroid or long-acting beta-agonist prevention
• Hospitalization in the 2 years prior to entry
• A history of chronic congestive heart failure or other significant cardiac condition.
• Any active clinically significant medical condition that, in the opinion of the site investigator, would place the participant at increased risk.
• History of non-infectious pneumonitis within the last 5 years prior to study entry.
• Retinopathy or uveitis within 180 days prior to study entry.
• Any acute or chronic psychiatric diagnoses that, in the opinion of the investigator, make the participant ineligible for participation.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (8)

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

12201, Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, 91350-200, Brazil

Location

12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, Brazil

Location

Toronto General Hospital CRS

Toronto, Ontario, M5G 2N2, Canada

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site # 31802)

Bangkok, 6850, Thailand

Location

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (Site ID: 31784)

Chiang Mai, 50200, Thailand

Location

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Debika Bhattacharya, MD

  UCLA CARE Center CRS

  STUDY CHAIR

• Jordan Feld, MD, PhD

  University Health Network / Toronto Centre for Liver Disease

  STUDY CHAIR

• Raymond T. Chung, MD

  Massachusetts General Hospital CRS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 6, 2019
• Study Start: January 1, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data."

Locations

US (3); BR (2); TH (2); CA (1)