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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; Hepatitis B
• Intervention / Treatment: Drug: Placebo; Drug: Selgantolimod

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jennifer Price, MD, PhD; Phone Number: 415-502-1429; Email: jennifer.price@ucsf.edu

Study Locations

• Botswana
  • South-East District
    • Gaborone, South-East District, Botswana
      • Not yet recruiting
      • Gaborone CRS
• Brazil
  • Porto Alegre, Brazil, 91350-200
    • Not yet recruiting
    • Hospital Nossa Senhora da Conceicao CRS
  • Rio De Janeiro, Brazil, 21040-360
    • Not yet recruiting
    • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS Site ID# 12101
    • Contact: Brenda Hoagland, M.D.; Phone Number: 55-21-38659122; Email: brenda.hoagland@ini.fiocruz.br
  • Rio de Janeiro, Brazil, 21040-360
    • Not yet recruiting
    • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
• Haiti
  • Port-au-Prince, Haiti, HT-6110
    • Not yet recruiting
    • GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
• Peru
  • Lima, Peru, 04
    • Not yet recruiting
    • Barranco CRS
• Philippines
  • Cavite, Philippines, 4114
    • Not yet recruiting
    • De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)
• South Africa
  • Durban, South Africa, 4091
    • Not yet recruiting
    • Durban International CRS
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Not yet recruiting
      • Soweto ACTG CRS
• Thailand
  • Chiang Mai, Thailand, 50200
    • Not yet recruiting
    • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 10330
      • Not yet recruiting
      • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
      • Contact: Parawee Thongpaeng; Phone Number: 106 662-6523040; Email: parawee.t@hivnat.org
• Uganda
  • Kampala, Uganda
    • Not yet recruiting
    • Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Not yet recruiting
      • Alabama CRS
      • Contact: Faye Heard, M.P.H.; Phone Number: 205-996-4405; Email: fhoward@uabmc.edu
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • UCSD Antiviral Research Center CRS
    • San Francisco, California, United States, 94143
      • Recruiting
      • Univ of California, San Francisco
    • Torrance, California, United States, 90502
      • Not yet recruiting
      • Harbor-UCLA Med. Ctr. CRS (Site ID: 603)
      • Contact: Mario Guerrero; Phone Number: 7318 424-201-3000; Email: mguerrero@lundquist.org
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20005
      • Not yet recruiting
      • Whitman-Walker Health CRS
      • Contact: Avery Anna Wimpelberg, B.A., CCRC; Phone Number: 202-797-3589; Email: AWimpelberg@whitman-walker.org
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Not yet recruiting
      • The Ponce de Leon Center CRS
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University CRS
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Not yet recruiting
      • Johns Hopkins University CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Massachusetts General Hospital CRS (MGH CRS)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University Therapeutics (WT) CRS
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Not yet recruiting
      • New Jersey Medical School Clinical Research Center CRS
  • New York
    • New York, New York, United States, 10032-3732
      • Not yet recruiting
      • Columbia P&S CRS
    • New York, New York, United States, 10065
      • Not yet recruiting
      • Weill Cornell Uptown CRS
    • New York, New York, United States, 10011
      • Recruiting
      • Weill Cornell Chelsea CRS
    • Rochester, New York, United States, 14642
      • Not yet recruiting
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS
      • Contact: Susan Hulse; Phone Number: 585-275-0529; Email: susan_hulse@urmc.rochester.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • Chapel Hill CRS
    • Greensboro, North Carolina, United States, 27401
      • Not yet recruiting
      • Greensboro CRS
  • Ohio
    • Cincinnati, Ohio, United States, 452292899
      • Not yet recruiting
      • Cincinnati Children's Hosp / Univ Hosp
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Case CRS Site ID# 2501
      • Contact: Julie Pasternak, R.N.; Phone Number: 216-844-2738; Email: pasternak.julie@clevelandactu.org
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • Ohio State University CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Penn Therapeutics CRS
      • Contact: Jamie Doyle, MPH, CCRC; Phone Number: 215-615-2316; Email: Jamie.Doyle1@pennmedicine.upenn.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Univ of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Not yet recruiting
      • Vanderbilt Therapeutics (VT) CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Houston AIDS Research Team CRS
      • Contact: Maria Laura Martinez; Phone Number: 713-500-6718; Email: Maria.L.Martinez@uth.tmc.edu
  • Washington
    • Seattle, Washington, United States, 98104-9929
      • Not yet recruiting
      • University of Washington AIDS CRS
• Zimbabwe
  • Harare
    • Milton Park, Harare, Zimbabwe
      • Not yet recruiting
      • Milton Park CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Selgantolimod 3 mg once weekly for 24 weeks	Drug: Selgantolimod; 1.5 mg tablet
Placebo Comparator: Arm B; Matching Placebo for Selgantolimod once weekly for 24 weeks	Drug: Placebo; Matching placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Estimated): January 19, 2025
• Study Completion (Estimated): July 17, 2025

Study Registration Dates

• First Submitted: September 9, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic
• Other Study ID Numbers: A5394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH
• IPD Sharing Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No