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)

NCT03434353 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-464-4437
• Study Type: interventional
• Target: 123
• Locations: 2 countries
• Sites: 13

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).

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (2)

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

  Baseline, Week 12

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

  Baseline, Week 12

Secondary Outcomes (11)

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

  Baseline, Week 12

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

  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)

  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)

  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)

  Baseline, Weeks 12, 24, 36, and 48

Study Arms (5)

Group 1: Inarigivir Soproxil 50 mg + TAF

EXPERIMENTAL

Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks.

Drug: Inarigivir Soproxil; Drug: TAF

Group 2: TAF

EXPERIMENTAL

Viremic participants will be administered TAF 25 mg tablet once daily orally with food for 48 weeks.

Drug: TAF

Group 3: Inarigivir Soproxil 200 mg + TAF

EXPERIMENTAL

Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks

Drug: Inarigivir Soproxil; Drug: TAF

Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs

EXPERIMENTAL

Virally suppressed participants receiving commercially available nucleoside/nucleotide (NUC) will be administered inarigivir soproxil 100 mg tablet once daily orally 1 hour before or 1 hour after a meal for 12 weeks. Participants will continue commercially available NUCs for 48 weeks.

Drug: Inarigivir Soproxil

Group 5: Inarigivir Soproxil 400 mg + TAF

EXPERIMENTAL

Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks.

Drug: Inarigivir Soproxil; Drug: TAF

Interventions

Inarigivir Soproxil DRUG

Administered orally once daily one hour before or one hour after a meal

Also known as: SB 9200, GS-9992

Group 1: Inarigivir Soproxil 50 mg + TAF; Group 3: Inarigivir Soproxil 200 mg + TAF; Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs; Group 5: Inarigivir Soproxil 400 mg + TAF

TAF DRUG

Administered orally once daily with food

Also known as: GS-7340, Vemlidy®

Group 1: Inarigivir Soproxil 50 mg + TAF; Group 2: TAF; Group 3: Inarigivir Soproxil 200 mg + TAF; Group 5: Inarigivir Soproxil 400 mg + TAF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead
• F-star Therapeutics, Inc.: collaborator

Study Sites (13)

Alice Ho Miu Ling Nethersole Hospital

Hong Kong, Hong Kong

Location

Prince Margaret Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital-HK

Hong Kong, Hong Kong

Location

Korea University Ansan Hospital

Ansan, 425-707, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 41931, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Inje University Ilsan Paik Hospital

Ilsan, 10380, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

Location

Catholic University of Korea, Seoul Saint Mary's Hospital

Seoul, 06591, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: February 28, 2018
• Primary Completion: January 20, 2020
• Study Completion: January 26, 2021
• Last Updated: April 4, 2022
• Results First Posted: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10); HK (3)