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

Overview

The study aims to assess safety and tolerability of oral toll-like receptor (TLR) 8 agonist Selgantolimod (SLGN) administered for 24 weeks in participants with both CHB and HIV who have been receiving suppressive antiviral therapy for both viruses for ≥5 years and have qHBsAg level >1000 (3 log10) IU/mL at screening. The study will also evaluate if TLR8 stimulation with SLGN will reduce hepatitis B surface antigen (HBsAg) titers in the blood.

Full Title of Study: “Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: January 19, 2025

Detailed Description

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.

Interventions

• Drug: Selgantolimod
  • 1.5 mg tablet
• Drug: Placebo
  • Matching placebo tablet

Arms, Groups and Cohorts

• Experimental: Arm A
  • Selgantolimod 3 mg once weekly for 24 weeks
• Placebo Comparator: Arm B
  • Matching Placebo for Selgantolimod once weekly for 24 weeks

Clinical Trial Outcome Measures

Primary Measures

• Proportion of participants who experienced adverse events (AEs)
  • Time Frame: From study treatment initiation to Week 24
• Proportion of participants who prematurely discontinued treatment due to adverse events (AEs)
  • Time Frame: From study treatment initiation to Week 24
• Proportion of participants with ≥1 log10 IU/mL decline from baseline in quantitative HBsAg (qHBsAg) after SLGN treatment at Week 24
  • Time Frame: At week 24

Secondary Measures

• Proportion of participants with ≥1 log10 IU/mL decline from baseline in qHBsAg at any time during the study after SLGN treatment Initiation
  • Time Frame: Baseline though week 48
• Proportion of participants with ≥0.5 log10 IU/mL decline from baseline in qHBsAg after SLGN treatment at Week 24
  • Time Frame: At week 24
• Proportion of participants with ≥0.5 log10 IU/mL decline in qHBsAg from baseline at any time during the study after SLGN treatment initiation
  • Time Frame: Baseline though week 48
• Proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up
  • Time Frame: Baseline though week 48
• Changes from baseline in qHBsAg levels at Weeks 4, 12, 24, 36, and 48
  • Time Frame: At week 4, 12, 24, 36 and 48
• Proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study
  • Time Frame: Baseline though week 48
• Proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study
  • Time Frame: Baseline though week 48
• Proportion of hepatitis B surface antibody (anti-HBs) negative participants at baseline who develop anti-HBs at any time during the study
  • Time Frame: Baseline though week 48
• Detection of plasma HIV RNA >50 copies/mL at weeks 2, 4, 24, and 48
  • Time Frame: At Weeks 2, 4, 24 and 48
• Detection of serum HBV DNA >50 IU/mL at weeks 2, 4, 24, and 48
  • Time Frame: At Weeks 2, 4, 24 and 48

Participating in This Clinical Trial

Inclusion Criteria

1. HIV-1 infection 2. 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. 3. CD4+ cell count ≥350 cells/mm3 4. 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. 5. Positive or negative HBeAg 6. Negative anti-HDV 7. Current CHB infection 8. 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. 9. Quantitative HBsAg >1000 IU/mL 10. Hepatitis C virus (HCV) antibody negative, or if the participant is HCV antibody positive, an undetectable HCV RNA. 11. Participants age ≥18 years and ≤70 years at study entry 12. Participants must agree to stay on an effective antiviral therapy for HIV (ART) and HBV throughout the study. Exclusion Criteria:

1. Receipt of treatment for HCV within 24 weeks prior to study entry 2. Evidence of advanced fibrosis or cirrhosis (Metavir ≥F3 or equivalent). 3. Current or prior history of clinical hepatic decompensation (e.g., ascites, encephalopathy, or variceal hemorrhage) 4. History of HCC or cholangiocarcinoma 5. 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. 6. History of solid organ transplantation 7. Presence of any active or acute AIDS-defining opportunistic infections within 60 days prior to study entry 8. History of uveitis or posterior synechiae 9. Breastfeeding

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • National Institute of Allergy and Infectious Diseases (NIAID)
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Contact(s)
  • Jennifer Price, MD, PhD, 415-502-1429, jennifer.price@ucsf.edu