Hepatitis b VirusPhase 1NCT05856890
HepB mAb19 in Individuals With Chronic Hepatitis B Infection
A Phase 1 study testing HepB mAb19 and Sterile Saline in people with Hepatitis b Virus and Hepatitis B, run by Rockefeller University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis b Virus, Hepatitis B
- What is being tested?
- HepB mAb19 and Sterile Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 Apr 2024to 30 Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
NYU Langone Health
New York, New York, 10016
The Rockefeller University
New York, New York, 10065
About this study
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
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).
Read the 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.
- Conditions
- Hepatitis b Virus, Hepatitis B
- Being tested
- HepB mAb19, Sterile Saline
- Keywords
- monoclonal antibody, HBV, HepB mAb19
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
Sterile SalineOther
Placebo will be normal sterile saline (NaCl 0.9%).
| Study group | Role | What they receive |
|---|---|---|
| Group 1a: HepB mAb19 1 mg/kg, IV | Experimental | Single intravenous infusion of HepB mAb19, dosed at 1 mg/kg. Receives: Biological: HepB mAb19 |
| Group 2a: HepB mAb19 3 mg/kg, IV | Experimental | Single intravenous infusion of HepB mAb19, dosed at 3 mg/kg. Receives: Biological: HepB mAb19 |
| Group 3a: HepB mAb19 10 mg/kg, IV | Experimental | Single intravenous infusion of HepB mAb19, dosed at 10 mg/kg. Receives: Biological: HepB mAb19 |
| Group 4a: HepB mAb19 30 mg/kg, IV | Experimental | Single intravenous infusion of HepB mAb19, dosed at 30 mg/kg. Receives: Biological: HepB mAb19 |
| Group 5: Maximum tolerated dose, IV | Experimental | Single intravenous infusion of HepB mAb19, dosed at the MTD Receives: Biological: HepB mAb19 |
| Group 1b: Placebo 1 mg/kg, IV | Placebo comparator | Single intravenous infusion of placebo - normal saline, dosed at 1 mg/kg. Receives: Other: Sterile Saline |
| Group 2b: Placebo 3 mg/kg, IV | Placebo comparator | Single intravenous infusion of placebo - normal saline, dosed at 3 mg/kg. Receives: Other: Sterile Saline |
| Group 3b: Placebo 10 mg/kg, IV | Placebo comparator | Single intravenous infusion of placebo - normal saline, dosed at 10 mg/kg. Receives: Other: Sterile Saline |
| Group 4b: Placebo 30 mg/kg, IV | Placebo comparator | Single intravenous infusion of placebo - normal saline, dosed at 30 mg/kg. Receives: Other: Sterile Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 48 weeks
Changes in AST within 2,12, 24 and 48 weeks after administration.
Changes in AST will be assessed after IP administration
Measured: 48 weeks
Changes in ALT within 2,12, 24 and 48 weeks after administration
Changes in ALT will be assessed after IP administration
Measured: 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
Measured: 48 weeks
Changes in bilirubin within 2,12, 24 and 48 weeks after administration
Changes in bilirubin will be assessed after IP administration
Measured: 48 weeks
Changes in albumin within 2,12, 24 and 48 weeks after administration
Changes in albumin will be assessed after IP administration
Measured: 48 weeks
Elimination half-life of HepB mAb19
Elimination half-life (t1/2) will be assessed after IP administration
Measured: 48 weeks
Clearance (CL/F) of HepB mAb19
Clearance (CL/F) will be assessed after IP administration
Measured: 48 weeks
Volume of Distribution (Vz/F) of HepB mAb19
Volume of Distribution (Vz/F) will be assessed after IP administration
Measured: 48 weeks
Area under the curve (AUC) of HepB mAb19
Area under the curve (AUC) will be assessed after IP administration
Measured: 48 weeks
Decay Curve of HepB mAb19
Decay Curve will be assessed after IP administration
Measured: 48 weeks
Secondary outcomes (4)
Rate and severity of treatment-related adverse events during study follow up.
The occurrence of treatment-related AEs will be assessed after IP administration.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2023
- Study start25 Apr 2024
- Primary completion7 Jul 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis b VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Collaborators
- NYU Langone Health
- Responsible party
- Principal investigator, Marina Caskey, MD, Rockefeller University
- Investigators
- Marina Caskey, MD, Principal investigator, The Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05856890
- Sponsor's protocol ID
- RUHBV1
- Other IDs
- MCA-1037
- Status last verified
- Oct 2026
- First submitted
- 19 Apr 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32504577