Study of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV

A5394 is a phase II, double-blinded, placebo-controlled trial. Forty-eight study participants will be randomized 3:1 to receive SLGN or its placebo (36 active and 12 placebo), and randomization will be stratified by HBeAg status. One-half of the study participants will be HBeAg positive (n=24) at screening, and the other half will be HBeAg negative (n=24). All participants will remain on their non-study-provided antiviral therapy throughout the study.

Inclusion criteria

• HIV-1 infection
• Effective antiviral therapy for HIV (ART) and HBV that includes TDF, TAF, TDF/FTC, TDF/3TC (tenofovir disoproxil fumarate plus lamivudine), TAF/FTC, or entecavir (ETV), for ≥5 years immediately prior to study entry. ART is defined as including a minimum of two anti-HIV antivirals.
• CD4+ cell count ≥350 cells/mm3
• HIV-1 RNA <50 copies/mL measured on at least two occasions at least 12 weeks apart, with no documented value >200 copies/mL, over the 12 months prior to study entry.
• Positive or negative HBeAg
• Negative anti-HDV
• Current CHB infection
• HBV DNA level <50 IU/mL measured on at least two occasions at least 12 weeks apart, with no documented value ≥50 IU/mL, over the 12 months prior to study entry.
• Quantitative HBsAg >1000 IU/mL
• Hepatitis C virus (HCV) antibody negative, or if the participant is HCV antibody positive, an undetectable HCV RNA.
• Participants age ≥18 years and ≤70 years at study entry
• Participants must agree to stay on an effective antiviral therapy for HIV (ART) and HBV throughout the study.

Exclusion criteria

• Receipt of treatment for HCV within 24 weeks prior to study entry
• Evidence of advanced fibrosis or cirrhosis (Metavir ≥F3 or equivalent).
• Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy, or variceal hemorrhage)
• History of HCC or cholangiocarcinoma
• Malignancy within 5 years prior to study entry. NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) is not exclusionary.
• History of solid organ transplantation
• Presence of any active or acute AIDS-defining opportunistic infections within 60 days prior to study entry
• History of uveitis or posterior synechiae
• Breastfeeding