Safety and Antiviral Activity of a Monoclonal Hepatitis B Antibody (The SAMBA Study)

NCT06668727 | Recruiting Phase 1 DMC

• 2 other identifiers: SAMBA-0012023-508444-22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatitis B virus (HBV) remains a major global health problem with an estimated 257 million people living with the infection worldwide. Chronic HBV (CHB) is a major cause of liver cirrhosis and hepatocellular carcinoma. While antiviral therapies are available and suppress viral levels, treatment is long-term, does not clear the infection and rarely leads to long-term control once discontinued. Moreover, treatment access is not ideal on a global level with less than 10% of people in need receiving treatment. Although a strategy that eliminates all viral particles from the body represents the "holy grail" of HBV therapy, a strategy that leads to HBsAg loss and allows patients to stop treatment is highly desirable. New strategies to achieve either complete viral clearance or a state of viral control without the need for long-term treatment are being developed, including approaches to restore immune responses. Antibodies are key modulators of immune responses because of their dual functionality. In addition to directly targeting a viral antigen, antibodies differ from direct antivirals in that they can recruit other immune cells to eliminate infected cells and accelerate viral clearance. This study will evaluate the safety and pharmacokinetics of a monoclonal antibody that was isolated from an HBV-vaccinated individual, HepB mAb19, as well as its potential effects on viral levels and antiviral immune responses in individuals living with CHB.

Conditions

Hepatitis B

Keywords

Chronic hepatitis B; Experimental trial; Monoclonal antibodies

Outcome Measures

Primary Outcomes (8)

• Safety and tolerability

  Safety and tolerability evaluation will be done by recording of adverse events. The DAIDS AE Grading Table Corrected version 2.1 (July 2017) will be used to grade adverse events. In addition, the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale will be used for reporting and grading adverse events related to infusion reactions and cytokine release syndromes within 24 hours of the start of IP or placebo administration that are considered administration reactions or cytokine release syndromes.

  From enrollment to the end of follow up at 48 weeks

• Pharmacokinetic profile

  HepB mAb19 levels in serum will be measured by a validated sandwich ELISA method developed and performed by Celldex Therapeutics. HepB mAb19 levels will be measured before and at the end of the administration, at 3 and 6 hours, 1, 3, 7 days and on weeks 2, 3, 4 weeks after administration, and at later time points during follow up.

  From enrollment to the end of follow up at 48 weeks

• Pharmacokinetic profile

  Assesment of HepB mAb19 elimination half-life (t1/2)

  From enrollment to follow up at 48 weeks

• Pharmacokinetic profile

  Assesment of clearance (CL/F) of HepB mAb19

  From enrollment to follow up at 48 weeks

• Pharmacokinetic profile

  Calculation of volume of distribution (Vz/F)

  From enrollment to follow up at 48 weeks

• Pharmacokinetic profile

  Calculation of area under the curve (AUC) for HepB mAb19

  From enrollment to follow up at 48 weeks

• Pharmacokinetic profile

  Calculation of HepB mAb19 decay curve

  From enrollment to follow up at 48 weeks

• Maximum tolerated dose

  To establish the maximum tolerated dose (MDT)

  From enrollment to follow up at 48 weeks

Secondary Outcomes (2)

• HBsAg levels

  From enrollment to the end of follow up at 48 weeks

• HepB mAb19 antibodies

  From enrollment to the end of follow up at 48 weeks

Other Outcomes (5)

• HBV markers

  From enrollment to the end of follow up at 48 weeks

• HbsAg and HbeAg seroconversion

  From enrollment to the end of follow up at 48 weeks

• HBV specific immune responses

  From enrollment to the end of follow up at 48 weeks

Study Arms (4)

Group 1

EXPERIMENTAL

Participants (n=4), will be enrolled in Group 1 (HepB mAb19 3 mg/kg or placebo, single dose) and randomized 3:1 to HepB mAb19 or placebo with each participant being dosed at least 72 hours apart. Following enrollment and administration of study drug in the first two participants, the Protocol Safety Review Team (PSRT) will review available safety data (including safety labs) and only following this review and in the absence of dose limiting toxicities (DLT), the remaining two participants in Group 1 will be enrolled and randomized to HepB mAb19 or placebo.

Drug: HepB mAb19

Group 2

EXPERIMENTAL

Participants (n=4), will be enrolled in Group 2 (HepB mAb19 10 mg/kg or placebo, single dose) and randomized 3:1 to HepB mAb19 or placebo with each participant being dosed at least 72 hours apart.

Drug: HepB mAb19

Group 3

EXPERIMENTAL

Participants (n=4), will be enrolled in Group 2 (HepB mAb19 30 mg/kg or placebo, single dose) and randomized 3:1 to HepB mAb19 or placebo with each participant being dosed at least 72 hours apart.

Drug: HepB mAb19

Group 4

EXPERIMENTAL

Participants (n=18) will enroll in Group 4 in an open-label fashion and will receive the MTD. Enrollment in Group 4 will begin after all 4 participants enrolled in the preceding dose group reach at least 28 days, none of the dose escalating halting criteria outlined above occur, and following review of available safety data by the PSRT

Drug: HepB mAb19

Interventions

HepB mAb19 DRUG

The study has two parts: Part A will involve administering a single ascending dose of HepB mAb19 or placebo using a randomized, double-blind method in Groups 1-3 at dose levels of 3, 10, and 30 mg/kg. Participants enrolled in Groups 1-3 will be randomized at a 3:1 ratio to receive HepB mAb19 or placebo. Part B will assess the maximum tolerated dose (MTD) in Group 4 in an openlabel fashion. Participants will receive HepB mAb19 at MTD.

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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 49 days prior to study entry (day 0):
• HBV DNA below lower limit of quantification;
• 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, one of which must be from the highly effective methods for contraception listed below. Barrier methods of contraception are permitted for the second method of contraception. Contraception must be used from 10 days prior to study entry and during study follow up. Acceptable methods of contraception include:
• Contraceptive subdermal implant;
• Intrauterine device or intrauterine system;
• Combined estrogen and progestogen oral contraceptive;
• Injectable progestogen;
• Contraceptive vaginal ring;

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) 12 months prior to entry or done at the pre-infusion visit. Note: If FibroScan results are not available, imaging will be performed at the preinfusion visit.
• Presence of a LI-RADS4 or 5 liver lesion on imaging 12 months prior to entry or done at pre-infusion visit, if prior results not available.
• Alpha fetoprotein \>20 ng/ml. Note: Alpha-fetoprotein (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 12 months prior to 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 Electrocardiogram (ECG) abnormalities based on the average of the triplicate ECG recordings (e.g., 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 6 months prior to entry;
• History of chronic liver disease from another cause, ICD, 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 2 weeks prior to entry.
• Laboratory abnormalities in the parameters listed below:
• Absolute neutrophil count \<1,000 /mm3
• Hemoglobin \<10 gm/dL (6.21 mmol/L)
• Platelet count \<150,000 /mm3

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

Department of Infectious Diseases, Aarhus University Hospital

Aarhus N, 8200, Denmark

RECRUITING

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ole S. Søgaard, MD, Professor

  Infectious Diseases, Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ole Schmeltz Søgaard, MD, Professor

CONTACT

004527215985; olesoega@rm.dk

Thomas Rasmussen, MD, PhD

CONTACT

004593801394; thomrasm@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 31, 2024
• Study Start: August 26, 2024
• Primary Completion (Estimated): August 26, 2027
• Study Completion (Estimated): August 26, 2027
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)