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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)

Primary Purpose

Chronic Hepatitis B

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Inarigivir Soproxil
TAF
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1: Inarigivir Soproxil 50 mg + TAF

Group 2: TAF

Group 3: Inarigivir Soproxil 200 mg + TAF

Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs

Group 5: Inarigivir Soproxil 400 mg + TAF

Arm Description

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.

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

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

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5)
Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)

Secondary Outcome Measures

Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5)
Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
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.
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.
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.
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.
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)
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
Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)
Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)

Full Information

First Posted
February 9, 2018
Last Updated
March 8, 2022
Sponsor
Gilead Sciences
Collaborators
F-star Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03434353
Brief Title
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated due to sponsor's decision to not pursue further development of inarigivir soproxil in chronic hepatitis B.
Study Start Date
February 28, 2018 (Actual)
Primary Completion Date
January 20, 2020 (Actual)
Study Completion Date
January 26, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
F-star Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Inarigivir Soproxil 50 mg + TAF
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2: TAF
Arm Type
Experimental
Arm Description
Viremic participants will be administered TAF 25 mg tablet once daily orally with food for 48 weeks.
Arm Title
Group 3: Inarigivir Soproxil 200 mg + TAF
Arm Type
Experimental
Arm Description
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
Arm Title
Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 5: Inarigivir Soproxil 400 mg + TAF
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Inarigivir Soproxil
Other Intervention Name(s)
SB 9200, GS-9992
Intervention Description
Administered orally once daily one hour before or one hour after a meal
Intervention Type
Drug
Intervention Name(s)
TAF
Other Intervention Name(s)
GS-7340, Vemlidy®
Intervention Description
Administered orally once daily with food
Primary Outcome Measure Information:
Title
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
Title
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 Outcome Measure Information:
Title
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
Title
Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
Time Frame
Baseline, Week 12
Title
Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)
Description
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
Title
Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4)
Description
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
Title
Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)
Description
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
Title
Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4)
Description
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
Title
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
Title
Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4)
Description
Virologic breakthrough was defined as HBV deoxyribonucleic acid (DNA) ≥69 IU/mL for 2 consecutive visits
Time Frame
Baseline up to Week 12
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Alice Ho Miu Ling Nethersole Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Prince Margaret Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Prince of Wales Hospital-HK
City
Hong Kong
Country
Hong Kong
Facility Name
Korea University Ansan Hospital
City
Ansan
ZIP/Postal Code
425-707
Country
Korea, Republic of
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
41931
Country
Korea, Republic of
Facility Name
Kyungpook National University Hospital
City
Daegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Inje University Ilsan Paik Hospital
City
Ilsan
ZIP/Postal Code
10380
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Gangnam Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
06273
Country
Korea, Republic of
Facility Name
Catholic University of Korea, Seoul Saint Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
SMG-SNU Boramae Medical Center
City
Seoul
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
ZIP/Postal Code
08308
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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.
Results Reference
result

Learn more about this trial

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)

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