HepB mAb19 for Chronic Hepatitis B

Recruiting at 1 trial location

Overseen By Marina Caskey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rockefeller University

Must be taking: Nucleos(t)ide analogs

Must not be taking: Systemic corticosteroids, Immunosuppressive

Disqualifiers: Advanced fibrosis, HIV, HCV, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

37 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Do I need to stop my current medications for the trial?

The trial requires participants to continue their current HBV-active nucleos(t)ide therapy without changes for at least 3 months before joining. The protocol does not specify if other medications need to be stopped.

What safety data exists for HepB mAb19 or similar treatments?

The safety of hepatitis B vaccines, which may be similar to HepB mAb19, has been generally accepted, though some adverse reactions like injection site reactions and allergic reactions have been reported. Serious events are rare and not clearly linked to the vaccine, and the benefits are considered to outweigh the risks. ^{1 2 3 4 5}

Research Team

Marina Caskey, MD

Principal Investigator

The Rockefeller University

Eligibility Criteria

Adults aged 18-70 with chronic Hepatitis B on nucleos(t)ide therapy for at least 6 months can join. They must not be pregnant, agree to use contraception, and have a stable viral load. Excluded are those with severe allergies, heart disease, recent acute infections, advanced liver fibrosis or cancerous liver lesions.

Inclusion Criteria

I have been on stable hepatitis B treatment for at least 6 months.

I am between 18 and 70 years old.

Negative serum or urine pregnancy test at screening and on day 0 for participants who can become pregnant

Exclusion Criteria

HIV-1, HCV or hepatitis delta virus infection within 12 months from entry or done at screen

I haven't taken steroids, immunosuppressants, or certain cancer drugs in the last 6 months.

Confirmed significant allergic reactions against any drug, monoclonal antibody or vaccine, or multiple drug allergies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of HepB mAb19 or placebo at one of four increasing dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, pharmacokinetics, and antiviral activity for 48 weeks after infusion

48 weeks

Treatment Details

Interventions

• HepB mAb19

Trial Overview The trial is testing HepB mAb19, an experimental antibody targeting the hepatitis B virus in patients already on standard treatment. It's compared against a placebo (sterile saline). The study will look at safety and how well it works to control the virus.

Participant Groups

Group I: Group 5: Maximum tolerated dose, IV Experimental Treatment 1 Intervention

Single intravenous infusion of HepB mAb19, dosed at the MTD

Group II: Group 4a: HepB mAb19 30 mg/kg, IV Experimental Treatment 1 Intervention

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

Group III: Group 3a: HepB mAb19 10 mg/kg, IV Experimental Treatment 1 Intervention

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

Group IV: Group 2a: HepB mAb19 3 mg/kg, IV Experimental Treatment 1 Intervention

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

Group V: Group 1a: HepB mAb19 1 mg/kg, IV Experimental Treatment 1 Intervention

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

Group VI: Group 2b: Placebo 3 mg/kg, IV Placebo Group 1 Intervention

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

Group VII: Group 1b: Placebo 1 mg/kg, IV Placebo Group 1 Intervention

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

Group VIII: Group 4b: Placebo 30 mg/kg, IV Placebo Group 1 Intervention

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

Group IX: Group 3b: Placebo 10 mg/kg, IV Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Rockefeller University

Lead Sponsor

Trials

162

Recruited

16,700+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Findings from Research

In a study involving 43,618 Alaska natives who received 101,360 doses of the hepatitis B vaccine, only 39 individuals reported possible adverse reactions, indicating a low incidence of serious side effects.

The most common adverse reactions were mild and included prolonged myalgia/arthralgia, skin rashes, and dizziness, with no increased risk of Guillain-Barré syndrome found among vaccine recipients, supporting the vaccine's overall safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons. McMahon, BJ., Helminiak, C., Wainwright, RB., et al.[2019]

The Hepatitis A Inactivated and Hepatitis B Recombinant Vaccine (HEPAB), approved by the FDA in May 2001, received 305 reports of adverse events from May 2001 to September 2003, with most being non-serious like local reactions and constitutional symptoms.

Serious adverse events were reported, but a thorough review found no clear causal relationship with the vaccine, aside from injection site reactions and some allergic responses, indicating that HEPAB is generally safe for immunization in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events after hepatitis A B combination vaccine. Woo, EJ., Miller, NB., Ball, R.[2006]

A total of 20,231 adverse event reports were received following hepatitis B vaccinations from 2005 to 2015, with the most common side effects being dizziness and nausea for single antigen vaccines, and fever and injection site erythema for combination vaccines.

The review found no new or unexpected safety concerns with the current hepatitis B vaccines, but highlighted the need for improved training for healthcare providers to prevent vaccination errors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015. Haber, P., Moro, PL., Ng, C., et al.[2018]

The recombinant hepatitis B vaccine is generally considered safe and effective in preventing hepatitis B infection, which is a major cause of liver disease worldwide, but it may contain components that could be linked to autoimmune diseases in susceptible individuals.

Despite the potential risks, the overall benefits of the hepatitis B vaccine outweigh its risks, and it is important for patients and physicians to discuss these factors when considering vaccination, while also encouraging reporting of any adverse reactions for further research and safety improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of hepatitis B vaccination. Geier, MR., Geier, DA., Zahalsky, AC.[2019]

Out of 1771 neonatal death reports following Hepatitis B vaccination, only 18 deaths were identified, suggesting a very low incidence of fatalities associated with the vaccine among neonates.

The majority of the autopsied cases (12 out of 17) were attributed to sudden infant death syndrome, indicating that there is no clear causal link between HepB vaccination and neonatal deaths, especially given the extensive use of the vaccine in over 86 million doses since 1991.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal deaths after hepatitis B vaccine: the vaccine adverse event reporting system, 1991-1998. Niu, MT., Salive, ME., Ellenberg, SS.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events after hepatitis A B combination vaccine. [2006]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A review of hepatitis B vaccination. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Neonatal deaths after hepatitis B vaccine: the vaccine adverse event reporting system, 1991-1998. [2019]