Study to Evaluate the Safety and Antiviral Activity of Inarigivir Soproxil (Formerly: GS-9992) Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Adults With Chronic Hepatitis B (CHB)

Phase 2TerminatedNCT03434353

Gilead Sciences123 enrolled

Overview

The primary objectives of this study are to evaluate the safety and tolerability of the 12 week treatment regimens of inarigivir soproxil plus tenofovir alafenamide (TAF) or commercially available nucleoside/nucleotide (NUC) in adults with chronic hepatitis B (CHB), to evaluate the antiviral activity of 12 weeks of inarigivir soproxil plus TAF versus TAF alone in viremic CHB participants (Groups 1-3, 5), and to evaluate the antiviral activity of 12 weeks of inarigivir soproxil with commercially available NUC(s) in virally suppressed CHB participants (Group 4).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

123

Conditions

Chronic Hepatitis B

Interventions

Inarigivir Soproxil

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Groups 1-3 and 5: * Individuals not taking any prescribed hepatitis B virus (HBV) NUC treatment * Group 4: * HBV deoxyribonucleic acid (DNA) ≤ 20 IU/mL at Screening by Central Lab. * Have been on a commercially available HBV NUC treatment(s) Key Exclusion Criteria: * Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV). * Extensive bridging fibrosis or cirrhosis * Evidence of hepatocellular carcinoma on imaging * Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage). * Chronic liver disease of a non-HBV etiology * Current alcohol or substance abuse Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (13)

Alice Ho Miu Ling Nethersole Hospital

Hong Kong, Hong Kong

Prince Margaret Hospital

Hong Kong, Hong Kong

Prince of Wales Hospital-HK

Hong Kong, Hong Kong

Korea University Ansan Hospital

Ansan, South Korea

Keimyung University Dongsan Medical Center

Daegu, South Korea

Kyungpook National University Hospital

Daegu, South Korea

Inje University Ilsan Paik Hospital

Ilsan, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, South Korea

...and 3 more locations

Outcomes

Primary Outcomes

Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5)

Time frame: Baseline, Week 12

Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)

Time frame: Baseline, Week 12

Secondary Outcomes

Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5)

Time frame: Baseline, Week 12

Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)

Time frame: Baseline, Week 12

Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)

HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. HBeAg seroconversion was defined as HBeAb changing from negative or missing at baseline to positive at any postbaseline visit. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4)

Time frame: Baseline, Weeks 12, 24, 36, and 48

Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)

HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. Participants who had missing information were assumed to have no HBeAg loss.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4)

HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit.

Time frame: Baseline, Weeks 12, 24, 36, and 48

Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Had HBV DNA ≥ 69 IU/mL (Groups 1 Through 3 and 5)

Time frame: Baseline, Week 48

Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4)

Virologic breakthrough was defined as HBV deoxyribonucleic acid (DNA) ≥69 IU/mL for 2 consecutive visits

Time frame: Baseline up to Week 12

Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)

Time frame: Baseline, Weeks 12, 16, 24, 36, and 48

Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)

Time frame: Baseline, Weeks 12, 16, 24, 36, and 48

Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)

Time frame: Baseline, Weeks 12, 16, 24, 36, and 48