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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
37
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 will be normal sterile saline (NaCl 0.9%).
NYU Langone Health
New York, New York, United States
RECRUITINGThe Rockefeller University
New York, New York, United States
RECRUITINGRate 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 48 weeks
Changes in AST within 2,12, 24 and 48 weeks after administration.
Changes in AST will be assessed after IP administration
Time frame: 48 weeks
Changes in ALT within 2,12, 24 and 48 weeks after administration
Changes in ALT will be assessed after IP administration
Time frame: 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
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Time frame: 48 weeks
Changes in bilirubin within 2,12, 24 and 48 weeks after administration
Changes in bilirubin will be assessed after IP administration
Time frame: 48 weeks
Changes in albumin within 2,12, 24 and 48 weeks after administration
Changes in albumin will be assessed after IP administration
Time frame: 48 weeks
Elimination half-life of HepB mAb19
Elimination half-life (t1/2) will be assessed after IP administration
Time frame: 48 weeks
Clearance (CL/F) of HepB mAb19
Clearance (CL/F) will be assessed after IP administration
Time frame: 48 weeks
Volume of Distribution (Vz/F) of HepB mAb19
Volume of Distribution (Vz/F) will be assessed after IP administration
Time frame: 48 weeks
Area under the curve (AUC) of HepB mAb19
Area under the curve (AUC) will be assessed after IP administration
Time frame: 48 weeks
Decay Curve of HepB mAb19
Decay Curve will be assessed after IP administration
Time frame: 48 weeks
Rate and severity of treatment-related adverse events during study follow up.
The occurrence of treatment-related AEs will be assessed after IP administration.
Time frame: 48 weeks
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.
Time frame: 48 weeks
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.
Time frame: 48 weeks
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.
Time frame: 48 weeks