search
Back to results

HepB mAb19 in Individuals With Chronic Hepatitis B Infection

Primary Purpose

Hepatitis b Virus

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
HepB mAb19
Sterile Saline
Sponsored by
Rockefeller University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis b Virus focused on measuring monoclonal antibody, HBV

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • NYU Langone Health
  • The Rockefeller UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Placebo Comparator

Placebo Comparator

Arm Label

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

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

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

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

Group 5: Maximum tolerated dose, IV

Group 1b: Placebo 1 mg/kg, IV

Group 2b: Placebo 3 mg/kg, IV

Group 3b: Placebo 10 mg/kg, IV

Group 4b: Placebo 30 mg/kg, IV

Arm Description

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

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

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

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

Single intravenous infusion of HepB mAb19, dosed at the MTD

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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
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
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
Changes in AST within 2,12, 24 and 48 weeks after administration.
Changes in AST will be assessed after IP administration
Changes in ALT within 2,12, 24 and 48 weeks after administration
Changes in ALT will be assessed after IP administration
Changes in alkaline phosphatase within 2,12, 24 and 48 weeks after administration
Changes in alkaline phosphatase will be assessed after IP administration
Changes in bilirubin within 2,12, 24 and 48 weeks after administration
Changes in bilirubin will be assessed after IP administration
Changes in albumin within 2,12, 24 and 48 weeks after administration
Changes in albumin will be assessed after IP administration
Elimination half-life of HepB mAb19
Elimination half-life (t1/2) will be assessed after IP administration
Clearance (CL/F) of HepB mAb19
Clearance (CL/F) will be assessed after IP administration
Volume of Distribution (Vz/F) of HepB mAb19
Volume of Distribution (Vz/F) will be assessed after IP administration
Area under the curve (AUC) of HepB mAb19
Area under the curve (AUC) will be assessed after IP administration
Decay Curve of HepB mAb19
Decay Curve will be assessed after IP administration

Secondary Outcome Measures

Rate and severity of treatment-related adverse events during study follow up.
The occurrence of treatment-related AEs will be assessed after IP administration.
Rate of induced anti-HepB mAb19 antibodies in all study groups.
Occurrence of anti-HepB mAb19 antibodies will be assessed at baseline and after IP administration.
Change in quantitative HBsAg levels from baseline (day 0) at each scheduled follow up visit.
Serum HBsAg levels will be measured from baseline (day 0) until end of study follow up.
Detection of HBsAg by a qualitative assay at each scheduled follow up visit.
Qualitative measure of HBsAg will be performed from baseline (day 0) until end of study follow up.

Full Information

First Posted
April 19, 2023
Last Updated
August 7, 2023
Sponsor
Rockefeller University
Collaborators
NYU Langone Health
search

1. Study Identification

Unique Protocol Identification Number
NCT05856890
Brief Title
HepB mAb19 in Individuals With Chronic Hepatitis B Infection
Official Title
A Phase 1, Placebo-controlled, Dose-escalation Study of the Safety, Pharmacokinetics, and Antiviral Activity of a Potent Neutralizing Monoclonal Antibody in Individuals With Chronic Hepatitis B Infection
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 7, 2023 (Actual)
Primary Completion Date
May 15, 2026 (Anticipated)
Study Completion Date
May 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rockefeller University
Collaborators
NYU Langone Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis b Virus
Keywords
monoclonal antibody, HBV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
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)
Allocation
Randomized
Enrollment
37 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1a: HepB mAb19 1 mg/kg, IV
Arm Type
Experimental
Arm Description
Single intravenous infusion of HepB mAb19, dosed at 1 mg/kg.
Arm Title
Group 2a: HepB mAb19 3 mg/kg, IV
Arm Type
Experimental
Arm Description
Single intravenous infusion of HepB mAb19, dosed at 3 mg/kg.
Arm Title
Group 3a: HepB mAb19 10 mg/kg, IV
Arm Type
Experimental
Arm Description
Single intravenous infusion of HepB mAb19, dosed at 10 mg/kg.
Arm Title
Group 4a: HepB mAb19 30 mg/kg, IV
Arm Type
Experimental
Arm Description
Single intravenous infusion of HepB mAb19, dosed at 30 mg/kg.
Arm Title
Group 5: Maximum tolerated dose, IV
Arm Type
Experimental
Arm Description
Single intravenous infusion of HepB mAb19, dosed at the MTD
Arm Title
Group 1b: Placebo 1 mg/kg, IV
Arm Type
Placebo Comparator
Arm Description
Single intravenous infusion of placebo - normal saline, dosed at 1 mg/kg.
Arm Title
Group 2b: Placebo 3 mg/kg, IV
Arm Type
Placebo Comparator
Arm Description
Single intravenous infusion of placebo - normal saline, dosed at 3 mg/kg.
Arm Title
Group 3b: Placebo 10 mg/kg, IV
Arm Type
Placebo Comparator
Arm Description
Single intravenous infusion of placebo - normal saline, dosed at 10 mg/kg.
Arm Title
Group 4b: Placebo 30 mg/kg, IV
Arm Type
Placebo Comparator
Arm Description
Single intravenous infusion of placebo - normal saline, dosed at 30 mg/kg.
Intervention Type
Biological
Intervention Name(s)
HepB mAb19
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Sterile Saline
Intervention Description
Placebo will be normal sterile saline (NaCl 0.9%).
Primary Outcome Measure Information:
Title
Rate and severity of solicited adverse events that are Grade 2 or above within 2 weeks after administration.
Description
The occurrence of solicited AEs will be assessed 2 weeks after IP administration.
Time Frame
2 weeks
Title
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.
Description
The occurrence of treatment-emerging AEs will be assessed after IP administration
Time Frame
48 weeks
Title
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.
Description
The occurrence of SAEs will be assessed after IP administration
Time Frame
48 weeks
Title
Rate and severity of participants with potential immune complex disease (ICD) throughout the study period following investigational product (IP) administration.
Description
The occurrence of immune complex disease will be assessed after IP administration
Time Frame
48 weeks
Title
Changes in AST within 2,12, 24 and 48 weeks after administration.
Description
Changes in AST will be assessed after IP administration
Time Frame
48 weeks
Title
Changes in ALT within 2,12, 24 and 48 weeks after administration
Description
Changes in ALT will be assessed after IP administration
Time Frame
48 weeks
Title
Changes in alkaline phosphatase within 2,12, 24 and 48 weeks after administration
Description
Changes in alkaline phosphatase will be assessed after IP administration
Time Frame
48 weeks
Title
Changes in bilirubin within 2,12, 24 and 48 weeks after administration
Description
Changes in bilirubin will be assessed after IP administration
Time Frame
48 weeks
Title
Changes in albumin within 2,12, 24 and 48 weeks after administration
Description
Changes in albumin will be assessed after IP administration
Time Frame
48 weeks
Title
Elimination half-life of HepB mAb19
Description
Elimination half-life (t1/2) will be assessed after IP administration
Time Frame
48 weeks
Title
Clearance (CL/F) of HepB mAb19
Description
Clearance (CL/F) will be assessed after IP administration
Time Frame
48 weeks
Title
Volume of Distribution (Vz/F) of HepB mAb19
Description
Volume of Distribution (Vz/F) will be assessed after IP administration
Time Frame
48 weeks
Title
Area under the curve (AUC) of HepB mAb19
Description
Area under the curve (AUC) will be assessed after IP administration
Time Frame
48 weeks
Title
Decay Curve of HepB mAb19
Description
Decay Curve will be assessed after IP administration
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Rate and severity of treatment-related adverse events during study follow up.
Description
The occurrence of treatment-related AEs will be assessed after IP administration.
Time Frame
48 weeks
Title
Rate of induced anti-HepB mAb19 antibodies in all study groups.
Description
Occurrence of anti-HepB mAb19 antibodies will be assessed at baseline and after IP administration.
Time Frame
48 weeks
Title
Change in quantitative HBsAg levels from baseline (day 0) at each scheduled follow up visit.
Description
Serum HBsAg levels will be measured from baseline (day 0) until end of study follow up.
Time Frame
48 weeks
Title
Detection of HBsAg by a qualitative assay at each scheduled follow up visit.
Description
Qualitative measure of HBsAg will be performed from baseline (day 0) until end of study follow up.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Recruitment Specialist
Phone
800-782-2737
Email
rucares@rockefeller.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Marina Caskey, MD
Phone
212-327-7396
Email
mcaskey@rockefeller.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marina Caskey, MD
Organizational Affiliation
The Rockefeller University
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ira Jacobson, MD
Phone
212-263-3095
Email
ira.jacobson@nyulangone.org
Facility Name
The Rockefeller University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Recruitment Specialist
Phone
800-782-2737
Email
rucares@rockefeller.edu
First Name & Middle Initial & Last Name & Degree
Marina Caskey, MD
First Name & Middle Initial & Last Name & Degree
Katrina Millard, NP
First Name & Middle Initial & Last Name & Degree
Martina Turroja, MD
First Name & Middle Initial & Last Name & Degree
Deanna Dong, NP

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32504577
Citation
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.
Results Reference
background

Learn more about this trial

HepB mAb19 in Individuals With Chronic Hepatitis B Infection

We'll reach out to this number within 24 hrs