NCT05856890

Brief Summary

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).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
23mo left

Started Aug 2023

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Aug 2023Mar 2028

First Submitted

Initial submission to the registry

April 19, 2023

Completed
23 days until next milestone

First Posted

Study publicly available on registry

May 12, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

August 7, 2023

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2028

Last Updated

February 2, 2026

Status Verified

January 1, 2026

Enrollment Period

4.3 years

First QC Date

April 19, 2023

Last Update Submit

January 29, 2026

Conditions

Hepatitis b VirusHepatitis B

Keywords

monoclonal antibodyHBVHepB mAb19

Outcome Measures

Primary Outcomes (14)

  • Rate and severity of solicited adverse events that are Grade 2 or above within 2 weeks after administration.

    The occurrence of solicited AEs will be assessed 2 weeks after IP administration.

    2 weeks

  • Rate and severity of treatment-emerging unsolicited adverse events that are Grade 2 or above (including confirmed laboratory abnormalities) within 2, 12, 24 and 48 weeks after administration.

    The occurrence of treatment-emerging AEs will be assessed after IP administration

    48 weeks

  • Rate and severity of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and the duration of those SAEs.

    The occurrence of SAEs will be assessed after IP administration

    48 weeks

  • Rate and severity of participants with potential immune complex disease (ICD) throughout the study period following investigational product (IP) administration.

    The occurrence of immune complex disease will be assessed after IP administration

    48 weeks

  • Changes in AST within 2,12, 24 and 48 weeks after administration.

    Changes in AST will be assessed after IP administration

    48 weeks

  • Changes in ALT within 2,12, 24 and 48 weeks after administration

    Changes in ALT will be assessed after IP administration

    48 weeks

  • Changes in alkaline phosphatase within 2,12, 24 and 48 weeks after administration

    Changes in alkaline phosphatase will be assessed after IP administration

    48 weeks

  • Changes in bilirubin within 2,12, 24 and 48 weeks after administration

    Changes in bilirubin will be assessed after IP administration

    48 weeks

  • Changes in albumin within 2,12, 24 and 48 weeks after administration

    Changes in albumin will be assessed after IP administration

    48 weeks

  • Elimination half-life of HepB mAb19

    Elimination half-life (t1/2) will be assessed after IP administration

    48 weeks

  • Clearance (CL/F) of HepB mAb19

    Clearance (CL/F) will be assessed after IP administration

    48 weeks

  • Volume of Distribution (Vz/F) of HepB mAb19

    Volume of Distribution (Vz/F) will be assessed after IP administration

    48 weeks

  • Area under the curve (AUC) of HepB mAb19

    Area under the curve (AUC) will be assessed after IP administration

    48 weeks

  • Decay Curve of HepB mAb19

    Decay Curve will be assessed after IP administration

    48 weeks

Secondary Outcomes (4)

  • Rate and severity of treatment-related adverse events during study follow up.

    48 weeks

  • Rate of induced anti-HepB mAb19 antibodies in all study groups.

    48 weeks

  • Change in quantitative HBsAg levels from baseline (day 0) at each scheduled follow up visit.

    48 weeks

  • Detection of HBsAg by a qualitative assay at each scheduled follow up visit.

    48 weeks

Study Arms (9)

Group 1a: HepB mAb19 1 mg/kg, IV

EXPERIMENTAL

Single intravenous infusion of HepB mAb19, dosed at 1 mg/kg.

Biological: HepB mAb19

Group 2a: HepB mAb19 3 mg/kg, IV

EXPERIMENTAL

Single intravenous infusion of HepB mAb19, dosed at 3 mg/kg.

Biological: HepB mAb19

Group 3a: HepB mAb19 10 mg/kg, IV

EXPERIMENTAL

Single intravenous infusion of HepB mAb19, dosed at 10 mg/kg.

Biological: HepB mAb19

Group 4a: HepB mAb19 30 mg/kg, IV

EXPERIMENTAL

Single intravenous infusion of HepB mAb19, dosed at 30 mg/kg.

Biological: HepB mAb19

Group 5: Maximum tolerated dose, IV

EXPERIMENTAL

Single intravenous infusion of HepB mAb19, dosed at the MTD

Biological: HepB mAb19

Group 1b: Placebo 1 mg/kg, IV

PLACEBO COMPARATOR

Single intravenous infusion of placebo - normal saline, dosed at 1 mg/kg.

Other: Sterile Saline

Group 2b: Placebo 3 mg/kg, IV

PLACEBO COMPARATOR

Single intravenous infusion of placebo - normal saline, dosed at 3 mg/kg.

Other: Sterile Saline

Group 3b: Placebo 10 mg/kg, IV

PLACEBO COMPARATOR

Single intravenous infusion of placebo - normal saline, dosed at 10 mg/kg.

Other: Sterile Saline

Group 4b: Placebo 30 mg/kg, IV

PLACEBO COMPARATOR

Single intravenous infusion of placebo - normal saline, dosed at 30 mg/kg.

Other: Sterile Saline

Interventions

HepB mAb19BIOLOGICAL

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).

Group 1a: HepB mAb19 1 mg/kg, IVGroup 2a: HepB mAb19 3 mg/kg, IVGroup 3a: HepB mAb19 10 mg/kg, IVGroup 4a: HepB mAb19 30 mg/kg, IVGroup 5: Maximum tolerated dose, IV
Sterile SalineOTHER

Placebo will be normal sterile saline (NaCl 0.9%).

Group 1b: Placebo 1 mg/kg, IVGroup 2b: Placebo 3 mg/kg, IVGroup 3b: Placebo 10 mg/kg, IVGroup 4b: Placebo 30 mg/kg, IV

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 \> 10 IU/mL;
  • HBs antibody 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.

You may not qualify if:

  • \- 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., 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
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

The Rockefeller University

New York, New York, 10065, United States

RECRUITING

Related Publications (1)

  • Wang Q, Michailidis E, Yu Y, Wang Z, Hurley AM, Oren DA, Mayer CT, Gazumyan A, Liu Z, Zhou Y, Schoofs T, Yao KH, Nieke JP, Wu J, Jiang Q, Zou C, Kabbani M, Quirk C, Oliveira T, Chhosphel K, Zhang Q, Schneider WM, Jahan C, Ying T, Horowitz J, Caskey M, Jankovic M, Robbiani DF, Wen Y, de Jong YP, Rice CM, Nussenzweig MC. A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations. Cell Host Microbe. 2020 Aug 12;28(2):335-349.e6. doi: 10.1016/j.chom.2020.05.010. Epub 2020 Jun 5.

    PMID: 32504577BACKGROUND

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitisLiver DiseasesDigestive System Diseases

Study Officials

  • Marina Caskey, MD

    The Rockefeller University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Recruitment Specialist

CONTACT

800-782-2737rucares@rockefeller.edu

Marina Caskey, MD

CONTACT

212-327-7396mcaskey@rockefeller.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
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)
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Clinical Investigation

Study Record Dates

First Submitted

April 19, 2023

First Posted

May 12, 2023

Study Start

August 7, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

March 30, 2028

Last Updated

February 2, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(2)