Purpose

This is a first-in-human, placebo-controlled, single dose, dose-escalation phase 1 study to evaluate the safety, pharmacokinetics and antiviral activity of a highly potent neutralizing anti-HBV monoclonal antibody (mAb), HepB mAb19, which targets the S-protein in individuals with chronic hepatitis B (CHB) on nucleos(t)ide analog therapy (NRTI).

Condition

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age 18 to 70; - HBV infection confirmed by positive HBsAg for >/= 6 months; - On HBV-active nucleos(t)ide therapy for >/= 6 months without change in NRTI in the previous 3 months; - The following laboratory values within 49 days from study entry (day 0): - HBV DNA below lower limit of quantification; - HBsAg </= 3,000 IU/mL; - HBs antibody negative; - HBeAg negative; - Ability and willingness to provide informed consent; - For participants who can become pregnant (i.e., participants who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative serum or urine pregnancy test at screening and on day 0 (study entry). - Participants who can become pregnant must agree to use two methods of contraception. - Partner sterilization with documentation of azoospermia prior to the participant's entry into the study, and this partner is the sole partner for that participant. The documentation of partner sterility can come from the site personnel's review of medical records or medical history interview provided by the participant or the partner. Self-reported documentation of reproductive potential should be entered in the source documents. - Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms from 10 days prior to study entry and during study follow up to avoid impregnating a partner who can get pregnant.

Exclusion Criteria

  • Clinical symptoms, imaging studies or liver histology suggestive of advanced fibrosis (exclude fibrosis grade 3 and 4 by FibroScan (Fibroscan┬«< 9 kpa) within 12 months from entry or done at the pre-infusion visit. Note: If FibroScan results from within 12 months are not available, imaging will be performed at the pre-infusion visit. - Presence of a LI-RADS4 or 5 liver lesion on imaging within 12 months from entry or done at pre-infusion visit, if prior results not available. - Alpha fetoprotein > 20 ng/ml Note: AFP above normal but < 20 is acceptable for entry if earlier AFP levels (older than 6 months) are within normal range and imaging is negative in last 3 months). - HIV-1, HCV or hepatitis delta virus infection within 12 months from entry or done at screen, if prior results not available. - History of hematopoietic stem cell transplant or solid organ transplant; - Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, monoclonal antibody or vaccine, or multiple drug allergies (non-active hay fever is acceptable); - History of cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death); - History or presence of clinically significant ECG abnormalities based on the average of the triplicate ECG recordings (e.g., PQ/PR interval > 210 ms, QT corrected for heart rate using the Fridericia's correction factor [QTcF] > 450 ms for males and QTcF > 470 ms for females); - History of systemic corticosteroids, immunosuppressive anti-cancer, systemic interferons or interleukins within the last 6 months; - History of chronic liver disease from another cause, immune complex disease, or autoimmune diseases that in the opinion of the investigator would preclude participation. - Any significant acute infection (e.g. influenza, COVID-19) or any other clinically significant illness within 2 weeks prior to Day 0. - Laboratory abnormalities in the parameters listed below: - Absolute neutrophil count < 1,000 /mm3 - Hemoglobin < 10 gm/dL - Platelet count < 150,000 /mm3 - ALT > 2.0 x ULN - AST > 2.0 x ULN - Total bilirubin > 1.5 ULN (except individuals with known Gilbert's) - Albumin < 3.5 gm/dL - Calculated creatinine clearance < 70 mL/min (using the Cockcroft Gault formula). - INR >/= 1.2 - Pregnancy or lactation; - Any vaccination within 14 days prior to IP administration; - Receipt of anti-HBV mAb therapy of any kind in the past (including HBIG); - Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
In Groups 1-4, eligible participants will be randomized at a 3:1 ratio to receive a single intravenous infusion of HepB mAb19 or placebo (normal saline) at one of four increasing dose levels (1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg). In Group 5 participants will receive HepB mAb19 at the maximum tolerated dose (MTD)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group 1a: HepB mAb19 1 mg/kg, IV
Single intravenous infusion of HepB mAb19, dosed at 1 mg/kg.
  • Biological: HepB mAb19
    HepB mAb19 is a human mAb of IgG1kappa isotype that specifically binds to the "a" determinant of the extracellular loop of the HBV surface antigen (HBsAg).
Experimental
Group 2a: HepB mAb19 3 mg/kg, IV
Single intravenous infusion of HepB mAb19, dosed at 3 mg/kg.
  • Biological: HepB mAb19
    HepB mAb19 is a human mAb of IgG1kappa isotype that specifically binds to the "a" determinant of the extracellular loop of the HBV surface antigen (HBsAg).
Experimental
Group 3a: HepB mAb19 10 mg/kg, IV
Single intravenous infusion of HepB mAb19, dosed at 10 mg/kg.
  • Biological: HepB mAb19
    HepB mAb19 is a human mAb of IgG1kappa isotype that specifically binds to the "a" determinant of the extracellular loop of the HBV surface antigen (HBsAg).
Experimental
Group 4a: HepB mAb19 30 mg/kg, IV
Single intravenous infusion of HepB mAb19, dosed at 30 mg/kg.
  • Biological: HepB mAb19
    HepB mAb19 is a human mAb of IgG1kappa isotype that specifically binds to the "a" determinant of the extracellular loop of the HBV surface antigen (HBsAg).
Experimental
Group 5: Maximum tolerated dose, IV
Single intravenous infusion of HepB mAb19, dosed at the MTD
  • Biological: HepB mAb19
    HepB mAb19 is a human mAb of IgG1kappa isotype that specifically binds to the "a" determinant of the extracellular loop of the HBV surface antigen (HBsAg).
Placebo Comparator
Group 1b: Placebo 1 mg/kg, IV
Single intravenous infusion of placebo - normal saline, dosed at 1 mg/kg.
  • Other: Sterile Saline
    Placebo will be normal sterile saline (NaCl 0.9%).
Placebo Comparator
Group 2b: Placebo 3 mg/kg, IV
Single intravenous infusion of placebo - normal saline, dosed at 3 mg/kg.
  • Other: Sterile Saline
    Placebo will be normal sterile saline (NaCl 0.9%).
Placebo Comparator
Group 3b: Placebo 10 mg/kg, IV
Single intravenous infusion of placebo - normal saline, dosed at 10 mg/kg.
  • Other: Sterile Saline
    Placebo will be normal sterile saline (NaCl 0.9%).
Placebo Comparator
Group 4b: Placebo 30 mg/kg, IV
Single intravenous infusion of placebo - normal saline, dosed at 30 mg/kg.
  • Other: Sterile Saline
    Placebo will be normal sterile saline (NaCl 0.9%).

Recruiting Locations

The Rockefeller University
New York, New York 10065
Contact:
Recruitment Specialist
800-782-2737
rucares@rockefeller.edu

More Details

Status
Recruiting
Sponsor
Rockefeller University

Study Contact

Recruitment Specialist
800-782-2737
rucares@rockefeller.edu

Detailed Description

The study has a dose escalation design. In Groups 1-4, eligible participants will be randomized at a 3:1 ratio to receive a single intravenous infusion of HepB mAb19 or placebo (normal saline) at one of four increasing dose levels (1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg). In Group 5 participants will receive HepB mAb19 at the maximum tolerated dose (MTD). Participants will be followed for 48 weeks after HepB mAb19 or placebo infusion.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.