Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 40
- 主要终点
- Proportion of participants who experienced adverse events (AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Arm B
Matching Placebo for Selgantolimod once weekly for 24 weeks
干预措施: Placebo (Drug)
Arm A
Selgantolimod 3 mg once weekly for 24 weeks
干预措施: Selgantolimod (Drug)
结局指标
主要结局
Proportion of participants who experienced adverse events (AEs)
时间窗: From study treatment initiation to Week 24
Proportion of participants who prematurely discontinued treatment due to adverse events (AEs)
时间窗: 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
时间窗: At week 24
次要结局
- 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)
- 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)
- 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)