Selgantolimod for Chronic Hepatitis B and HIV

Not currently recruiting at 45 trial locations

Overseen By Jennifer Price, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must be taking: Antivirals

Disqualifiers: Advanced fibrosis, Cirrhosis, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment called Selgantolimod for individuals with both chronic hepatitis B (CHB) and HIV. The main goal is to determine the safety of this treatment and its ability to lower levels of a hepatitis B marker (HBsAg) in the blood. Participants will receive either Selgantolimod or a placebo (a non-active substance) once a week for 24 weeks. The trial seeks individuals who have been on effective antiviral treatment for both conditions for at least five years and have specific levels of hepatitis B markers in their blood. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires participants to continue their current antiviral therapy for HIV and HBV throughout the study.

Is there any evidence suggesting that Selgantolimod is likely to be safe for humans?

Research has shown that selgantolimod is generally safe and well tolerated. In previous studies, participants took selgantolimod pills up to 3 mg once a week for 24 weeks. These studies found that selgantolimod was safe for most people and did not cause serious side effects.

Some participants experienced mild reactions, but these were not usually severe. Selgantolimod has also been tested with other medications for chronic hepatitis B, and it proved safe in those cases too. Overall, evidence suggests that selgantolimod is a safe option for people with chronic hepatitis B and HIV. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic hepatitis B and HIV?

Researchers are excited about Selgantolimod because it offers a new approach for treating chronic Hepatitis B and HIV. Unlike standard treatments that focus on suppressing the virus, Selgantolimod is a TLR8 agonist, which means it works by activating the immune system to fight off the infection itself. This novel mechanism of action could potentially lead to a functional cure, which is a significant advancement over current therapies that usually require lifelong treatment. Additionally, Selgantolimod is administered just once a week, which is more convenient than daily regimens, making it easier for patients to adhere to their treatment plans.

What evidence suggests that Selgantolimod might be an effective treatment for chronic hepatitis B and HIV?

Research has shown that selgantolimod, a type of medication, may help treat chronic hepatitis B (CHB). In animal studies, selgantolimod was safe and demonstrated long-lasting effects against the virus. In human studies, when combined with other antiviral treatments, selgantolimod slightly lowered hepatitis B surface antigen (HBsAg) levels in up to 20% of patients. This trial will evaluate selgantolimod's effectiveness for people with both CHB and HIV, with participants receiving either selgantolimod or a matching placebo. These findings support further research into its potential benefits. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-70 with chronic Hepatitis B and HIV, on effective antiviral therapy for both for over 5 years, having low HBV DNA levels and high HBsAg levels. They must have a stable immune status (CD4+ count ≥350 cells/mm3) and controlled HIV viral load. Excluded are those with recent HCV treatment, liver cancer or organ transplants, certain infections or advanced liver damage.

Inclusion Criteria

Quantitative HBsAg >1000 IU/mL

My hepatitis B surface antigen status is known.

HIV-1 RNA <50 copies/mL measured on at least two occasions at least 12 weeks apart

Exclusion Criteria

Breastfeeding

I have had liver or bile duct cancer.

I have been treated for hepatitis C within the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Selgantolimod or placebo once weekly for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selgantolimod

Trial Overview The trial is testing Selgantolimod, an oral drug that targets the immune system's TLR8 receptor. It's given to participants for 24 weeks to see if it can lower hepatitis B surface antigen levels in people who also have HIV but are already on suppressive antiviral therapy.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

Selgantolimod 3 mg once weekly for 24 weeks

Group II: Arm B Placebo Group 1 Intervention

Matching Placebo for Selgantolimod once weekly for 24 weeks

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a small study of 11 HIV-positive patients with chronic active viral hepatitis, a low dose combination of zidovudine and interferon alfa-2b led to significant improvements, including reduced liver enzyme levels and increased CD4 lymphocyte counts.

The treatment was well tolerated, with no observed progression of HIV disease, suggesting it may be a safe and effective option for managing both HIV and hepatitis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zidovudine plus interferon alfa-2b treatment in patients with HIV and chronic active viral hepatitis. Visco, G., Alba, L., Grisetti, S., et al.[2019]

In a pilot study involving 10 anti-HIV positive patients with chronic hepatitis B, interferon alfa was well-tolerated, showing similar safety profiles to those in anti-HIV negative patients.

Treatment with interferon alfa led to significant improvements in hepatitis B markers for some patients, including the disappearance of HBV-DNA and normalization of ALT levels, indicating potential efficacy in managing chronic hepatitis B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine. Marcellin, P., Boyer, N., Colin, JF., et al.[2019]

Approximately 10% of the 36 million people living with HIV globally are also infected with chronic hepatitis B virus (HBV), highlighting the significant overlap between these two infections.

Recent advancements in antiviral treatments for HBV and improved diagnostic tools have transformed the management of patients who are coinfected with HIV and HBV, allowing for better care and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. Soriano, V., Puoti, M., Peters, M., et al.[2022]

In a 3-year study of 39 patients, HBV isolates from HIV-coinfected individuals showed significantly fewer mutations in the basal core promoter (BCP) region compared to those from HBV-monoinfected patients, suggesting a more stable genomic pattern in the presence of HIV.

The study found that mutations in the precore (Pc) region were rare among all patients and appeared to be dependent on the HBV genotype rather than influenced by HIV co-infection, indicating that the impact of HIV on HBV may vary based on the specific viral strains involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B precore/core promoter mutations in isolates from HBV-monoinfected and HBV-HIV coinfected patients: a 3-yr prospective study. Cassino, L., Laufer, N., Salomon, H., et al.[2010]

HIV and hepatitis B coinfection is a significant public health issue, affecting the management and treatment outcomes for individuals with both infections.

Current treatment strategies focus on antiretroviral therapy that is effective against both HIV and hepatitis B, highlighting the importance of integrated care for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-1/hepatitis B coinfection. Benhamou, Y.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03615066

NCT03615066 | Study to Evaluate the Safety, Tolerability ... The primary objectives of this study are to evaluate the safety and tolerability of multiple oral doses of selgantolimod and to evaluate the antiviral ...

2. gileadclinicaltrials.com gileadclinicaltrials.com/study?id=GS-US-465-4439

Study to Evaluate the Safety and Efficacy of Selgantolimod ... The primary objectives of this study are to evaluate the safety and tolerability of study treatment(s) (selgantolimod-containing combination therapies)

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10808922/

Safety, pharmacodynamics, and antiviral activity of ... A study in the woodchuck model of CHB showed that 8 weeks of treatment with selgantolimod was well tolerated and induced sustained antiviral efficacy and loss ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05551273

NCT05551273 | Study of Oral TLR8 Agonist Selgantolimod ... The study aims to assess safety and tolerability of oral toll-like receptor (TLR) 8 agonist Selgantolimod (SLGN) administered for 24 weeks in participants ...

5. sigma.larvol.com sigma.larvol.com/product.php?e1=704781&tab=newstrac

selgantolimod (GS-9688) News Phase 2 study of selgantolimod in combination with nucleos(t)ide analogue in virologically suppressed patients showed mild decline of HBsAg in up to 20% of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38133554/

Safety and efficacy of the oral TLR8 agonist selgantolimod ... Conclusion: Oral selgantolimod up to 3 mg once weekly for 24 weeks was generally safe and well tolerated and led to serologic changes associated with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589555923003063

Safety, pharmacodynamics, and antiviral activity of ... Viremic patients with chronic HBV infection received SLGN+TAF for 24 weeks. •. SLGN therapy was safe and well tolerated. •. SLGN induced a transient increase in ...

8. actgnetwork.org actgnetwork.org/clinical-trial/a5394-safety-tolerability-and-impact-of-oral-tlr8-agonist-selgantolimod-on-hbsag/

A5394: Safety, Tolerability, and Impact of Oral TLR8 ... A5394: Safety, Tolerability, and Impact of Oral TLR8 Agonist Selgantolimod on HBsAg in Participants with Both Chronic Hepatitis B and HIV.