* HBV Cure Combination Ph2
Research type
Research Study
Full title
A Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)
IRAS ID
302699
Contact name
Kaushik Agarwal
Contact email
Eudract number
2021-000672-11
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Summary of Research
This is a phase 2a, open-label study to evaluate the safety and efficacy of Selgantolimod (SLGN)-containing combination therapies for the treatment of Chronic Hepatitis B (CHB). Selgantolimod is a Toll-like receptor 8 (TLR8) agonist which works to boost the immune system. CHB is a major public health care issue worldwide and causes chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The aim is to see if SLGN-containing combination therapies are safe and able to help participants immune systems to clear hepatitis B virus from their body.
Approximately 120 globally participants will be assigned to one of three cohorts, based on the nature of their CHB.
Cohort 1 will receive Tenofovir Alafenamide (TAF) by mouth, VIR-2218 via injection under the skin, SGLN by mouth and Nivolumab via infusion injection (taking 30-40 mins). These medications will be given at various doses and timepoints over 36 to 84 weeks.
There will be two groups in Cohort 2. They will receive VIR-2218 via injection under the skin, SGLN by mouth and/or Nivolumab via injection under the skin. These medications will be given at various doses and timepoints over 24-36 weeks (depending which group of the cohort they are in).
Cohort 3 will receive VIR-2218 via injection under the skin, SGLN by mouth and Nivolumab via injection under the skin. These medications will be given at various doses and timepoints over 24 weeks.
After completing study treatments all participants will undergo 48 weeks of FU.
The participants will visit the study site 21 times (cohort 1 & 2A) or 19 times (cohort 2B & 3), where they will undergo procedures such as medical history, chest x-ray, ophthalmologic examination, blood and urine tests and a physical examination including weight, height, temperature, heart rate, blood pressure, electrocardiogram (ECG). The study doctor will also review previous/current medications.
Summary of Results
The summary should be succinct and written in Plain English, using language easily understood by members of the public. Any technical terms should be explained. All acronyms should be described in full.
Multiple approved treatment options for patients with chronic hepatitis B virus (HBV) infection are available, but they rarely result in a cure. Investigating drug combinations may uncover a successful cure in the future. In this study, the combination of selgantolimod (SLGN) a TLR8 agonist, VIR-2218 (elebsiran) a small interfering RNA that targets the HBx region of the HBV genome, and nivolumab an anti–programmed cell death protein 1 monoclonal antibody, for chronic HBV cure led to overall low rates of functional cure in this study.
SLGN was generally well tolerated in combination with VIR-2218 and nivolumab. The majority of the adverse events (AEs) were treatment emergent (TE) and Grade 1 or Grade 2 in severity. Serious adverse events (SAEs) were infrequent, and none occurred in more than 1 participant. There were no deaths during the study.
The use of nivolumab in this study was associated with the emergence of immune-related adverse event (irAEs), with 7 irAEs considered related to nivolumab by the investigators, including 2 SAEs (immune-mediated hepatitis and Type 1 Diabetes Mellitus). Based on the emerging safety profile of nivolumab in this study, nivolumab dosing was discontinued early across all cohorts following a sponsor-driven benefit-risk assessment of the use of nivolumab in HBV cure.
REC name
London - Central Research Ethics Committee
REC reference
21/FT/0119
Date of REC Opinion
1 Nov 2021
REC opinion
Further Information Favourable Opinion