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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Recruiting
• CT.gov ID: NCT05551273
• Collaborator: (none)
• Enrollment: 48
• Locations: 36
• Arms: 2
• Anticipated Duration (Months): 22.6
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B; HIV Infections	Drug: Selgantolimod; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants With Both Chronic Hepatitis B and HIV
• Actual Study Start Date: Dec 14, 2022
• Anticipated Primary Completion Date: Mar 12, 2024
• Anticipated Study Completion Date: Nov 2, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Proportion of participants who experienced adverse events (AEs) [From study treatment initiation to Week 24]

2. Proportion of participants who prematurely discontinued treatment due to adverse events (AEs) [From study treatment initiation to Week 24]

3. 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

1. 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]

2. Proportion of participants with ≥0.5 log10 IU/mL decline from baseline in qHBsAg after SLGN treatment at Week 24 [At week 24]

3. 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]

4. Proportion of participants who achieve HBsAg loss after SLGN initiation and who sustain HBsAg loss during follow-up [Baseline though week 48]

5. Changes from baseline in qHBsAg levels at Weeks 4, 12, 24, 36, and 48 [At week 4, 12, 24, 36 and 48]

6. Proportion of HBeAg positive participants at baseline who lose HBeAg at any time during the study [Baseline though week 48]

7. Proportion of anti-HBe negative participants at baseline who develop anti-HBe at any time during the study [Baseline though week 48]

8. 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]

9. Detection of plasma HIV RNA >50 copies/mL at weeks 2, 4, 24, and 48 [At Weeks 2, 4, 24 and 48]

10. Detection of serum HBV DNA >50 IU/mL at weeks 2, 4, 24, and 48 [At Weeks 2, 4, 24 and 48]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Antiviral Research Center CRS	San Diego	California	United States	92103
2	Univ of California, San Francisco	San Francisco	California	United States	94143
3	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
4	University of Colorado Hospital CRS	Aurora	Colorado	United States	80045
5	Whitman-Walker Health CRS	Washington	District of Columbia	United States	20005
6	The Ponce de Leon Center CRS	Atlanta	Georgia	United States	30308
7	Northwestern University CRS	Chicago	Illinois	United States	60611
8	Johns Hopkins University CRS	Baltimore	Maryland	United States	21205
9	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts	United States	02114
10	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri	United States	63110
11	New Jersey Medical School Clinical Research Center CRS	Newark	New Jersey	United States	07103
12	Weill Cornell Chelsea CRS	New York	New York	United States	10011
13	Columbia P&S CRS	New York	New York	United States	10032-3732
14	Weill Cornell Uptown CRS	New York	New York	United States	10065
15	Chapel Hill CRS	Chapel Hill	North Carolina	United States	27599
16	Greensboro CRS	Greensboro	North Carolina	United States	27401
17	Cincinnati Children's Hosp / Univ Hosp	Cincinnati	Ohio	United States	452292899
18	Case CRS	Cleveland	Ohio	United States	44106
19	Ohio State University CRS	Columbus	Ohio	United States	43210
20	Penn Therapeutics CRS	Philadelphia	Pennsylvania	United States	19104
21	Univ of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
22	Vanderbilt Therapeutics (VT) CRS	Nashville	Tennessee	United States	37204
23	Houston AIDS Research Team CRS	Houston	Texas	United States	77030
24	University of Washington AIDS CRS	Seattle	Washington	United States	98104-9929
25	Gaborone CRS	Gaborone	South-East District	Botswana
26	Hospital Nossa Senhora da Conceicao CRS	Porto Alegre		Brazil	91350-200
27	Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS	Rio de Janeiro		Brazil	21040-360
28	GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS	Port-au-Prince		Haiti	HT-6110
29	Barranco CRS	Lima		Peru	04
30	De La Salle Health Science Institute Angelo King Medical Research Center (DLSHSI-AKMRC)	Cavite		Philippines	4114
31	Soweto ACTG CRS	Johannesburg	Gauteng	South Africa	1862
32	Durban International CRS	Durban		South Africa	4091
33	Thai Red Cross AIDS Research Centre (TRC-ARC) CRS	Pathum Wan	Bangkok	Thailand	10330
34	Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS	Chiang Mai		Thailand	50200
35	Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site	Kampala		Uganda
36	Milton Park CRS	Milton Park	Harare	Zimbabwe

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT05551273
• Other Study ID Numbers: A5394
• First Posted: Sep 22, 2022
• Last Update Posted: Feb 1, 2023
• Last Verified: Jan 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis

Study Results

No Results Posted as of Feb 1, 2023