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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV

Conditions
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Hepatitis B, HIV Infections

Intervention / Treatment
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* Drug: Selgantolimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Selgantolimod 3 mg once weekly for 24 weeks | Drug: Selgantolimod<br>* 1.5 mg tablet<br>|
| Placebo Comparator: Arm B<br>Matching Placebo for Selgantolimod once weekly for 24 weeks | Drug: Placebo<br>* Matching placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who experienced adverse events (AEs) |  | From study treatment initiation to Week 24 | 
| Proportion of participants who prematurely discontinued treatment due to 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |