Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir (SOF/VEL) Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX ) FDC for 12 Weeks in Adults With Chronic Hepatitis C Virus (HCV) Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04211909
• Collaborator: (none)
• Enrollment: 87
• Locations: 22
• Arms: 2
• Actual Duration (Months): 10.3
• Patients Per Site: 4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of therapy with Sofosbuvir/Velpatasvir (SOF/VEL) Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX ) FDC in participants with chronic HCV infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Infection	Drug: SOF/VEL; Drug: SOF/VEL/VOX	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic HCV Infection
• Actual Study Start Date: Jan 3, 2020
• Actual Primary Completion Date: Nov 12, 2020
• Actual Study Completion Date: Nov 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF/VEL Participants with chronic HCV infection (genotype 1 or 2), who are treatment-naive or treatment-experienced with interferon (IFN)-based treatments will receive SOF/VEL for 12 weeks.	Drug: SOF/VEL; 400/100 mg FDC tablet orally once daily.; Other Names: Epclusa® GS-7977/GS-5816
Experimental: SOF/VEL/VOX Participants with chronic HCV infection (genotype 1), who are treatment-experienced with nonstructural protein 5A (NS5A) direct-acting antiviral (DAA)-based treatments of at least 4 weeks duration will receive SOF/VEL/VOX for 12 weeks.	Drug: SOF/VEL/VOX; 400/100/100 mg FDC tablet orally once daily.; Other Names: Vosevi ® GS-7977/GS-5816/GS-9857

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < LLOQ (i.e., 15 IU/mL) at 12 weeks after stopping study treatment.

2. Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event [First dose date up to 12 weeks plus 30 days]

Secondary Outcome Measures

1. Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment [Posttreatment Week 4]

   SVR4 was defined as HCV RNA < LLOQ (i.e.15 IU/mL) 4 weeks after stopping study treatment.

2. Percentage of Participants With Virologic Failure [Baseline up to Posttreatment Week 12]

   Virologic failure was defined as: On-treatment virologic failure: Breakthrough (HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment ) Virologic relapse: • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit

3. Percentage of Participants With HCV RNA < LLOQ on Treatment [Week 2, Week 4, Week 8, Week 12]

   LLOQ was 15 IU/mL.

4. Change From Baseline in HCV RNA [Baseline, Week 2, Week 4, Week 8, Week 12]

5. Number of Participants With Alanine Aminotransferase (ALT) Normalization [Baseline, Week 2, Week 4, Week 8, Week 12]

   Number of participants with ALT normalization, defined as ALT > upper limit of normal (ULN) (ULN = 43 U/L) at baseline and ALT ≤ ULN, at each visit was presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Chronic HCV infected males and non-pregnant/non-lactating females

• Treatment-naive or treatment-experienced individuals

• Non-cirrhosis or compensated cirrhosis at screening

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-D	Korea, Republic of	13620
2	Inje University Busan Paik Hospital	Busan		Korea, Republic of	47392
3	Dong-A University Hospital	Busan		Korea, Republic of	48789
4	Pusan National University Hospital	Busan		Korea, Republic of	49241
5	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
6	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of	42601
7	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
8	Chosun University Hospital	Gwangju		Korea, Republic of	501-717
9	The Catholic University of Korea, Incheon St. Mary's Hospital	Incheon		Korea, Republic of	21431
10	Gachon University Gil Medical Center	Incheon		Korea, Republic of	405-760
11	Chonbuk National University Hospital	Jeonju		Korea, Republic of	54907
12	Seoul National University Hospital	Seoul		Korea, Republic of	03080
13	Severance Hospital	Seoul		Korea, Republic of	03722
14	VHS (Veterans Health Service) Medical Center	Seoul		Korea, Republic of	05368
15	Asan Medical Center	Seoul		Korea, Republic of	05505
16	Samsung Medical Center	Seoul		Korea, Republic of	06351
17	The Catholic University of Korea, Seoul Saint Mary's Hospital	Seoul		Korea, Republic of	06591
18	Chung-Ang University Hospital	Seoul		Korea, Republic of	06973
19	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
20	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
21	Ulsan University Hospital	Ulsan		Korea, Republic of	44033
22	Pusan National University Yangsan Hospital	Yangsan		Korea, Republic of	50612

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Oct 4, 2019
• Statistical Analysis Plan - Dec 10, 2020

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT04211909
• Other Study ID Numbers: GS-US-342-5532
• First Posted: Dec 26, 2019
• Last Update Posted: Oct 27, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis; Sofosbuvir; Velpatasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in South Korea. The first participant was screened on 03 January 2020. The last study visit occurred on 12 November 2020.
Pre-assignment Detail	96 participants were screened.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic hepatitis C virus (HCV) infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with interferon (IFN)-based treatments received sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with nonstructural protein 5A (NS5A) direct-acting antiviral (DAA)-based treatments of at least a 4 weeks duration received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (400/100/100 mg) FDC tablet orally once daily for 12 weeks.
Period Title: Overall Study
STARTED	54	33
COMPLETED	54	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	SOF/VEL	SOF/VEL/VOX	Total
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.	Total of all reporting groups
Overall Participants	54	33	87
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	34 63%	17 51.5%	51 58.6%
>=65 years	20 37%	16 48.5%	36 41.4%
Sex: Female, Male (Count of Participants)
Female	29 53.7%	18 54.5%	47 54%
Male	25 46.3%	15 45.5%	40 46%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	54 100%	33 100%	87 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	53 98.1%	33 100%	86 98.9%
Not Permitted	1 1.9%	0 0%	1 1.1%
Interleukin-28B gene (IL28b) Status (participants) [Number]
CC	41 75.9%	23 69.7%	64 73.6%
CT	13 24.1%	9 27.3%	22 25.3%
TT	0 0%	0 0%	0 0%
Missing	0 0%	1 3%	1 1.1%
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	24 44.4%	3 9.1%	27 31%
≥ 800,000 IU/mL	30 55.6%	30 90.9%	60 69%
Genotype (Count of Participants)
Genotype 1	27 50%	32 97%	59 67.8%
Genotype 2	27 50%	1 3%	28 32.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Study Treatment
Description	SVR12 was defined as HCV RNA < LLOQ (i.e., 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all enrolled participants who took at least 1 dose of study drug and had detectable HCV RNA at baseline.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Number (95% Confidence Interval) [percentage of participants]	98.1 181.7%	100 303%

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event
Time Frame	First dose date up to 12 weeks plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who took at least 1 dose of the study drug.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	54	33
Number [percentage of participants]	1.9 3.5%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With SVR < LLOQ 4 Weeks After Discontinuation of Study Treatment
Description	SVR4 was defined as HCV RNA < LLOQ (i.e.15 IU/mL) 4 weeks after stopping study treatment.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Number (95% Confidence Interval) [percentage of participants]	98.1 181.7%	100 303%

4. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as: On-treatment virologic failure: Breakthrough (HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment ) Virologic relapse: • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit
Time Frame	Baseline up to Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Number [percentage of participants]	1.9 3.5%	0 0%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ on Treatment
Description	LLOQ was 15 IU/mL.
Time Frame	Week 2, Week 4, Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Week 2	90.6 167.8%	69.7 211.2%
Week 4	100.0 185.2%	100.0 303%
Week 8	100.0 185.2%	100.0 303%
Week 12	100.0 185.2%	100.0 303%

6. Secondary Outcome

Title	Change From Baseline in HCV RNA
Time Frame	Baseline, Week 2, Week 4, Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Baseline	5.95 (0.866)	6.48 (0.354)
Change at Week 2	-4.78 (0.857)	-5.19 (0.545)
Change at Week 4	-4.81 (0.866)	-5.33 (0.354)
Change at Week 8	-4.79 (0.867)	-5.33 (0.354)
Change at Week 12	-4.79 (0.867)	-5.33 (0.354)

7. Secondary Outcome

Title	Number of Participants With Alanine Aminotransferase (ALT) Normalization
Description	Number of participants with ALT normalization, defined as ALT > upper limit of normal (ULN) (ULN = 43 U/L) at baseline and ALT ≤ ULN, at each visit was presented.
Time Frame	Baseline, Week 2, Week 4, Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL	SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A DAA-based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
Measure Participants	53	33
Baseline (ALT>ULN)	21 38.9%	16 48.5%
Week 2 (ALT≤ ULN)	21 38.9%	13 39.4%
Week 4 (ALT≤ ULN)	21 38.9%	13 39.4%
Week 8 (ALT≤ ULN)	19 35.2%	13 39.4%
Week 12 (ALT≤ ULN)	17 31.5%	13 39.4%

Adverse Events

Time Frame	From first dose date up to 12 weeks plus 30 days
Adverse Event Reporting Description	The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Arm/Group Title	SOF/VEL		SOF/VEL/VOX
Arm/Group Description	Participants with chronic HCV infection (genotype 1 or 2), who were treatment-naive or treatment-experienced with IFN-based treatments received SOF/VEL 400/100 mg FDC tablet orally once daily for 12 weeks.		Participants with chronic HCV infection (genotype 1 or 2), who were treatment-experienced with NS5A-DAA based treatments of at least a 4 weeks duration received SOF/VEL/VOX 400/100/100 mg FDC tablet orally once daily for 12 weeks.
All Cause Mortality
	SOF/VEL		SOF/VEL/VOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/33 (0%)
Serious Adverse Events
	SOF/VEL		SOF/VEL/VOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/54 (5.6%)		1/33 (3%)
Gastrointestinal disorders
Haematochezia	1/54 (1.9%)		0/33 (0%)
General disorders
Pyrexia	1/54 (1.9%)		0/33 (0%)
Injury, poisoning and procedural complications
Facial bones fracture	0/54 (0%)		1/33 (3%)
Nervous system disorders
Cerebral infarction	1/54 (1.9%)		0/33 (0%)
Skin and subcutaneous tissue disorders
Erythema nodosum	1/54 (1.9%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	SOF/VEL		SOF/VEL/VOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/54 (9.3%)		8/33 (24.2%)
Gastrointestinal disorders
Nausea	2/54 (3.7%)		3/33 (9.1%)
Nervous system disorders
Headache	4/54 (7.4%)		3/33 (9.1%)
Skin and subcutaneous tissue disorders
Rash	0/54 (0%)		3/33 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years