Phase 2
N=457
A Study of GSK3228836 in Participants With Chronic Hepatitis B (CHB)
Hepatitis B
Bottom Line
View on ClinicalTrials.gov: NCT04449029 ↗Enrolled (actual)
457
Serious AEs
3.7%
Results posted
May 2023
Primary outcome: Primary: Number of Participants Achieving Sustained Virologic Response (SVR) — 6; 6; 2; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK3228836 (Drug); Placebo (Drug); Nucleos(t)ide therapy (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Mar 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Achieving Sustained Virologic Response (SVR) |
6; 6; 2; 0; 7; 4 | — |
| SECONDARY Number of Participants Achieving HBsAg and HBV DNA<LLOQ |
16; 9; 8; 4; 17; 10 | — |
| SECONDARY Number of Participants With Categorical Changes From Baseline in HBsAg Values |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Categorical Changes From Baseline in HBV DNA Values |
66; 66; 66; 22; 0; 0 | — |
| SECONDARY Number of Participants With Alanine Aminotransferase (ALT) Normalization |
6; 7; 6; 2; 20; 20 | — |
| SECONDARY Median Time to ALT Normalization |
16.6; 4.1; 1; 7; 13.4; 15.1 | — |
| SECONDARY Number of Participants With Positive Hepatitis B Virus E-antibody (HBeAb) |
3; 4; 5; 2; 6; 4 | — |
| SECONDARY Mean HBsAg and HBV DNA Level |
3.29; 3.26; 3.33; 3.43; 3.72; 3.64 | — |
| SECONDARY Mean Values of Hepatitis B Virus e Antigen (HBeAg) Level |
0.49; 0.12; 0.36; 0.63; 2.13; 2.52 | — |
| SECONDARY Mean Change From Baseline in HBsAg and HBV DNA Level |
3.29; 3.26; 3.33; 3.43; 3.72; 3.64 | — |
| SECONDARY Mean Change From Baseline in HBeAg Level |
0.49; 0.12; 0.36; 0.63; 2.13; 2.52 | — |
| SECONDARY Mean Hepatitis B Virus Surface Antigen Antibody (Anti-HBsAg) Level |
0.67; 0.65; 0.64; 0.66; 0.65; 0.69 | — |
| SECONDARY Mean Change From Baseline in Anti-HBsAg Level |
0.67; 0.65; 0.64; 0.66; 0.65; 0.69 | — |
| SECONDARY Mean Area Under the Concentration-time Curve From Time 0 up to 24 Hours (AUC0-24h) of GSK3228836 |
55.214; 140.312 | — |
| SECONDARY Mean Maximum Observed Concentration (Cmax) of GSK3228836 |
6.112; 14.956 | — |
| SECONDARY Median Time of Maximum Observed Concentration (Tmax) of GSK3228836 |
3.008; 3.017 | — |
| SECONDARY Mean AUC0-24h of NA Therapies |
2753.908; 308.167; 24.43 | — |
| SECONDARY Mean Ctau of NA Therapies |
57.04; 10.31; 0.478 | — |
| SECONDARY Mean Cmax of NA Therapies |
318.857; 19.36; 6.526 | — |
| SECONDARY Median Tmax of NA Therapies |
1; 1.417; 0.983 | — |
| SECONDARY Median Terminal Half-life (t1/2) of GSK3228836 |
28.897; 24.918; 27.846; 38.205 | — |
| SECONDARY Mean Ctau of GSK3228836 |
21.009; 47.039; 21.663; 23.46; 23.162; 23.234 | — |
Summary
Chronic hepatitis B virus (HBV) infection is a significant worldwide medical problem. GSK3228836 demonstrated target engagement in CHB participants who were not on treatment and in CHB participants on stable nucleos(t)ide therapy. This study is intended to evaluate if treatment with GSK3228836 can achieve sustained virologic response (SVR), that is hepatitis B virus surface antigen (HBsAg) less than (<) lower limit of quantitation (LLOQ) and HBV deoxyribonucleic acid (DNA) <LLOQ sustained for 24 weeks post-GSK3228836 treatment end. In addition, the study will also evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of GSK3228836 in the 4 dosing regimens. This study will assess the efficacy and safety of treatment with GSK3228836 in two populations of participants with CHB; participants on stable nucleos(t)ide treatment (Cohort 1) and participants who are not currently on nucleos(t)ide therapy (Cohort 2). For each population, participants will be randomized into one of the 4 different parallel arms to receive treatment. The study will consist of a screening, treatment, and post-treatment follow-up phase. Approximately, 440 participants will be enrolled in the study.
Eligibility Criteria
Inclusion Criteria
- At least 18 years of age at the time of signing the informed consent.
- Participants who have documented chronic HBV infection greater than equal to (>=6) months prior to screening and not currently on nucleos(t)ide analogue therapy population defined as participants who never received HBV treatment (treatment naive) or must have ended nucleos(t)ide therapy at least 6 months prior to the screening visit; OR Currently receiving stable nucleos(t)ide analogue therapy population defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.
- Plasma or serum HBsAg concentration >100 international units per milliliter (IU/mL).
- Plasma or serum HBV DNA concentration: Participants not currently on nucleos(t)ide analogue therapy, plasma or serum HBV DNA >2000 IU/mL; Participants who are receiving stable nucleos(t)ide analogue therapy must be adequately suppressed, defined as plasma or serum HBV DNA 2 and FibroSure/FibroTest result >0.7. If only one parameter (APRI or FibroSure/FibroTest) result is positive, a discussion with the Medical Monitor is required before inclusion in study is permitted. Regardless of APRI of Fibrosure/FibroTest score, if the participant meets one of the following criteria, they will be excluded from the study: Liver biopsy (i.e., Metavir Score F4); Liver stiffness >12 kilopascals (kPa).
- Diagnosed or suspected hepatocellular carcinoma as evidenced by the following: Alpha-fetoprotein concentration >=200 nanogram per milliliter (ng/mL); If the screening alpha fetoprotein concentration is >=50 ng/mL and =450 milliseconds (msec) (if single electrocardiogram [ECG] at screening shows QTcF>=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).
- Laboratory results as follows: Serum albumin 1.25. Platelet count 1.25 times ULN. For participants with benign unconjugated hyperbilirubinemia with total bilirubin >1.25 times ULN, discussion for inclusion to the study is required with the Medical Monitor, Urine albumin to creatinine ratio (ACR) >=0.03 mg/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement. In cases where participants have low urine albumin and low urine creatinine levels resulting in a urine ACR calculation >=0.03 mg/mg (or >=30 mg/g), the investigator should confirm that the participant does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the Medical Monitor, or designee.
- History of/sensitivity to GSK3228836 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
Data sourced from ClinicalTrials.gov (NCT04449029). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.