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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05551273
• Other study ID #: A5394
• Status: Recruiting
• Phase: Phase 2
• Start date: May 5, 2023
• Est. completion date: July 17, 2025

Study information

• Verified date: May 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: Jennifer Price, MD, PhD
• Phone: 415-502-1429
• Email: jennifer.price[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: July 17, 2025
• Est. primary completion date: January 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• HIV Infections

Intervention

Drug:
• Selgantolimod
1.5 mg tablet
• Placebo
Matching placebo tablet

Locations

Country	Name	City	State
Botswana	Gaborone CRS	Gaborone	South-East District
Brazil	Hospital Nossa Senhora da Conceicao CRS	Porto Alegre
Brazil	Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS	Rio de Janeiro
Brazil	Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS Site ID# 12101	Rio De Janeiro
Haiti	GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS	Port-au-Prince
Peru	Barranco CRS	Lima
Philippines	De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)	Cavite
South Africa	Durban International CRS	Durban
South Africa	Soweto ACTG CRS	Johannesburg	Gauteng
Thailand	Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS	Chiang Mai
Thailand	Thai Red Cross AIDS Research Centre (TRC-ARC) CRS	Pathum Wan	Bangkok
Uganda	Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site	Kampala
United States	The Ponce de Leon Center CRS	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins University CRS	Baltimore	Maryland
United States	Alabama CRS	Birmingham	Alabama
United States	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts
United States	Chapel Hill CRS	Chapel Hill	North Carolina
United States	Northwestern University CRS	Chicago	Illinois
United States	Cincinnati Children's Hosp / Univ Hosp	Cincinnati	Ohio
United States	Case CRS Site ID# 2501	Cleveland	Ohio
United States	Ohio State University CRS	Columbus	Ohio
United States	Greensboro CRS Site# 3203	Greensboro	North Carolina
United States	Houston AIDS Research Team CRS	Houston	Texas
United States	Vanderbilt Therapeutics (VT) CRS	Nashville	Tennessee
United States	Columbia P&S CRS	New York	New York
United States	Weill Cornell Chelsea CRS	New York	New York
United States	Weill Cornell Uptown CRS	New York	New York
United States	New Jersey Medical School Clinical Research Center CRS	Newark	New Jersey
United States	Penn Therapeutics CRS	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Rochester Adult HIV Therapeutic Strategies Network CRS	Rochester	New York
United States	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri
United States	UCSD Antiviral Research Center CRS	San Diego	California
United States	Univ of California, San Francisco	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS (Site ID: 603)	Torrance	California
United States	Whitman-Walker Health CRS	Washington	District of Columbia
Zimbabwe	Milton Park CRS	Milton Park	Harare

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Zimbabwe,  Botswana,  Brazil,  Haiti,  Peru,  Philippines,  South Africa,  Thailand,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants who experienced adverse events (AEs)		From study treatment initiation to Week 24
Primary	Proportion of participants who prematurely discontinued treatment due to adverse events (AEs)		From study treatment initiation to Week 24
Primary	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	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
Secondary	Proportion of participants with =0.5 log10 IU/mL decline from baseline in qHBsAg after SLGN treatment at Week 24		At week 24
Secondary	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
Secondary	Proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up		Baseline though week 48
Secondary	Changes from baseline in qHBsAg levels at Weeks 4, 12, 24, 36, and 48		At week 4, 12, 24, 36 and 48
Secondary	Proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study		Baseline though week 48
Secondary	Proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study		Baseline though week 48
Secondary	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
Secondary	Detection of plasma HIV RNA >50 copies/mL at weeks 2, 4, 24, and 48		At Weeks 2, 4, 24 and 48
Secondary	Detection of serum HBV DNA >50 IU/mL at weeks 2, 4, 24, and 48		At Weeks 2, 4, 24 and 48