Hepatitis B, HIV Infections
Conditions
Brief summary
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.
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
DRUGSelgantolimod
1.5 mg tablet
DRUGPlacebo
Matching placebo tablet
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants who prematurely discontinued treatment due to adverse events (AEs) | From study treatment initiation to Week 24 |
| Proportion of participants who experienced adverse events (AEs) | 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 | At week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of participants with ≥1 log10 IU/mL decline from baseline in qHBsAg at any time during the study after SLGN treatment Initiation | Baseline though week 48 |
| Proportion of participants with ≥0.5 log10 IU/mL decline from baseline in qHBsAg after SLGN treatment at Week 24 | 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 | Baseline though week 48 |
| Proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up | Baseline though week 48 |
| Changes from baseline in qHBsAg levels at Weeks 4, 12, 24, 36, and 48 | At week 4, 12, 24, 36 and 48 |
| Proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study | Baseline though week 48 |
| Proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study | 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 | Baseline though week 48 |
| Detection of plasma HIV RNA >50 copies/mL at weeks 2, 4, 24, and 48 | At Weeks 2, 4, 24 and 48 |
| Detection of serum HBV DNA >50 IU/mL at weeks 2, 4, 24, and 48 | At Weeks 2, 4, 24 and 48 |
Countries
Brazil, Haiti, Peru, Philippines, South Africa, Thailand, United States, Zimbabwe
Outcome results
None listed