Clinical trial NCT03434353: 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)
Official title: A Phase 2, Randomized, Open-Label, Active-Controlled Study to Evaluate the Safety and Antiviral Activity of GS-9992 Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Chronic Hepatitis B (CHB) Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: F-star Therapeutics, Inc.
First posted: 2018-02-15
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5)
timeFrame: Baseline, Week 12
measure: Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5)
timeFrame: Baseline, Week 12
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
timeFrame: Baseline, Week 12
measure: Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4)
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4)
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: 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)
timeFrame: Baseline, Week 48
measure: Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4)
timeFrame: Baseline up to Week 12
measure: Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
timeFrame: Baseline, Weeks 12, 16, 24, 36, and 48
measure: Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
timeFrame: Baseline, Weeks 12, 16, 24, 36, and 48
measure: Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)
timeFrame: Baseline, Weeks 12, 16, 24, 36, and 48
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Alice Ho Miu Ling Nethersole Hospital
city: Hong Kong
country: Hong Kong
facility: Prince Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital-HK
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Ilsan
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Catholic University of Korea, Seoul Saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Lim YS, Hui AJ, Jang JW, Tak WY, Ahn SH, Jang BK, et al. Safety, efficacy, & pharmacodynamic (PD) activity of 12 weeks treatment with oral RIG-I agonist, inarigivir (IRIG), plus 48 weeks of tenofovir alafenamide in adult patients with chronic hepatitis B: a phase 2 collaboration study [Abstract PO-2422]. The International Liver Congress: European Association for the Study of the Liver (EASL) Virtual; 2021 23-26 June.