Safety and Antiviral Activity of a Monoclonal Hepatitis B Antibody: a First-in-human Phase 1, Placebo-controlled, Single Dose Escalation Clinical Trial in Individuals with Chronic Hepatitis B Infection (The SAMBA Study)
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.
• 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;
• Percutaneous contraceptive patches;
• 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.