Clinical trial NCT05551273: Study of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV
Official title: Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Hepatitis B
HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2022-09-22
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants who experienced adverse events (AEs)
timeFrame: From study treatment initiation to Week 24
measure: Proportion of participants who prematurely discontinued treatment due to adverse events (AEs)
timeFrame: From study treatment initiation to Week 24
measure: Proportion of participants with ≥1 log10 IU/mL decline from baseline in quantitative HBsAg (qHBsAg) after SLGN treatment at Week 24
timeFrame: At week 24
Secondary outcomes:
measure: Proportion of participants with ≥1 log10 IU/mL decline from baseline in qHBsAg at any time during the study after SLGN treatment Initiation
timeFrame: Baseline though week 48
measure: Proportion of participants with ≥0.5 log10 IU/mL decline from baseline in qHBsAg after SLGN treatment at Week 24
timeFrame: At week 24
measure: Proportion of participants with ≥0.5 log10 IU/mL decline in qHBsAg from baseline at any time during the study after SLGN treatment initiation
timeFrame: Baseline though week 48
measure: Proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up
timeFrame: Baseline though week 48
measure: Changes from baseline in qHBsAg levels at Weeks 4, 12, 24, 36, and 48
timeFrame: At week 4, 12, 24, 36 and 48
measure: Proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study
timeFrame: Baseline though week 48
measure: Proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study
timeFrame: Baseline though week 48
measure: Proportion of hepatitis B surface antibody (anti-HBs) negative participants at baseline who develop anti-HBs at any time during the study
timeFrame: Baseline though week 48
measure: Detection of plasma HIV RNA >50 copies/mL at weeks 2, 4, 24, and 48
timeFrame: At Weeks 2, 4, 24 and 48
measure: Detection of serum HBV DNA >50 IU/mL at weeks 2, 4, 24, and 48
timeFrame: At Weeks 2, 4, 24 and 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco HIV/AIDS CRS (801)
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS (Site ID: 603)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Health CRS
state: District of Columbia
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital CRS (MGH CRS)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center CRS
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS
state: New York
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: New York
country: United States
facility: Weill Cornell Uptown CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS Site# 3203
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hosp / Univ Hosp
state: Ohio
city: Cleveland
country: United States
facility: Case CRS Site ID# 2501
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS
state: Tennessee
city: Houston
country: United States
facility: Houston AIDS Research Team CRS
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: Gaborone
country: Botswana
facility: Gaborone CRS
state: South-East District
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao CRS
city: Rio De Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS Site ID# 12101
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
city: Port-au-Prince
country: Haiti
facility: GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
city: Lima
country: Peru
facility: Barranco CRS
city: Cavite
country: Philippines
facility: De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)
city: Johannesburg
country: South Africa
facility: Soweto ACTG CRS
state: Gauteng
city: Durban
country: South Africa
facility: Durban International CRS
city: Pathum Wan
country: Thailand
facility: Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
state: Bangkok
city: Chiang Mai
country: Thailand
facility: Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
city: Milton Park
country: Zimbabwe
facility: Milton Park CRS
state: Harare
Study officials:
References: