Principal Investigator: Ayotunde E. Omoz-Oarhe (MD, MPH)

Study Objectives:

Primary Objectives

• To assess the safety and tolerability of treatment with SLGN administered once weekly by mouth for 24 weeks.
• To determine the proportion of participants with ≥1 log10 IU/mL decline in quantitative HBsAg (qHBsAg) after SLGN treatment at Week 24.

Secondary Objectives

• To determine the proportion of participants with ≥1 log10 IU/mL decline in qHBsAg at any time during the study after SLGN treatment initiation.
• To determine the proportion of participants with ≥0.5 log10 IU/mL decline in qHBsAg after SLGN treatment at Week 24.
• To determine the proportion of participants with ≥0.5 log10 IU/mL decline in qHBsAg at any time during the study after SLGN treatment initiation.
• To evaluate the proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up.
• To evaluate changes in qHBsAg levels at Weeks 4, 12, 24, 36, and 48 after SLGN initiation and, separately, among the placebo recipients.
• To determine the proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study, by study arm.
• To determine the proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study, by study arm.
• To determine the proportion of hepatitis B surface antibody (anti-HBs) negative participants at baseline who develop anti-HBs at any time during the study, by study arm.
• To evaluate levels of circulating cytokines, including IFN-gamma, IL-12p40, IL-1RA, and CD163 at entry, 24 hours post-first study drug dose, Weeks 4, 12, 24, 36, and 48, by study arm.
• To determine whether administration of SLGN will perturb HIV latency as measured by an increase in HIV transcription.
• To determine whether administration of SLGN will decrease the size of the latent reservoir, as measured by the change in amount of cell-associated unspliced HIV RNA, HIV DNA, replication-competent and/or intact virus at Weeks 2, 4, 24, and 48.

Study Design:

A5394 is a phase II, randomized, double-blind, placebo-controlled clinical trial to assess the safety, tolerability, and efficacy of 24 weeks of treatment with SLGN.

People with HIV and Chronic Hepatitis B (24 HBeAg+, 24 HBeAg-) on suppressive, effective antiviral therapy for HIV (ART) and HBV will be randomized to active treatment with SLGN or matching placebo once weekly by mouth for 24 weeks. Random assignment of three active: one placebo will be stratified by HBeAg status. All participants will be followed for 48 weeks (24-week treatment phase and 24-week post-treatment follow-up). All treatment will be administered by DOT (in person and remotely).

Study population and Size:

Adult, males and female participants with both (1) HIV and chronic hepatitis B (CHB) on suppressive effective antiviral therapy for HIV (ART) and HBV for ≥5 years. The global sample size will be 48 participants (36 active and 12 placebos). Up to 6 additional participants may be enrolled if replacements are needed for key analyses. In Botswana, it is anticipated that a maximum of 10 participants will be enrolled.

Study duration: 12 to 18 Months

Study Results: Study is on-going and no data analyses have been done yet

Sponsor:

National Institute of Allergy and Infectious Diseases (NIH), Division of AIDS (DAIDS)