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)

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03434353
• Other study ID #: GS-US-464-4437
• Status: Terminated
• Phase: Phase 2
• Start date: February 28, 2018
• Est. completion date: January 26, 2021

Study information

• Verified date: March 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 123
• Est. completion date: January 26, 2021
• Est. primary completion date: January 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Inarigivir Soproxil
Administered orally once daily one hour before or one hour after a meal
• TAF
Administered orally once daily with food

Locations

Country	Name	City	State
Hong Kong	Alice Ho Miu Ling Nethersole Hospital	Hong Kong
Hong Kong	Prince Margaret Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital-HK	Hong Kong
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Inje University Ilsan Paik Hospital	Ilsan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Catholic University of Korea, Seoul Saint Mary's Hospital	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	F-star Therapeutics, Inc.

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of, 

References & 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:

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants With = 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)		Baseline, Week 12
Secondary	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
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)		Baseline, Week 12
Secondary	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.	Baseline, Weeks 12, 24, 36, and 48
Secondary	Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion 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. 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.	Baseline, Weeks 12, 24, 36, and 48
Secondary	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.	Baseline, Weeks 12, 24, 36, and 48
Secondary	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.	Baseline, Weeks 12, 24, 36, and 48
Secondary	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)		Baseline, Week 48
Secondary	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	Baseline up to Week 12
Secondary	Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)		Baseline, Weeks 12, 16, 24, 36, and 48
Secondary	Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)		Baseline, Weeks 12, 16, 24, 36, and 48
Secondary	Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)		Baseline, Weeks 12, 16, 24, 36, and 48