Sofosbuvir/Velpatasvir Fixed Dose Combination in Participants With Chronic Hepatitis C Virus Infection Who Have Received a Liver Transplant

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02781571
• Collaborator: (none)
• Enrollment: 79
• Locations: 15
• Arm: 1
• Actual Duration (Months): 12
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir /velpatasvir (SOF/VEL) fixed-dose combination (FDC) in participants with chronic hepatitis C virus (HCV) who have received a liver transplant.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Infection	Drug: SOF/VEL	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination in Subjects With Chronic HCV Infection Who Have Received a Liver Transplant
• Actual Study Start Date: Jul 27, 2016
• Actual Primary Completion Date: Jul 28, 2017
• Actual Study Completion Date: Jul 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF/VEL SOF/VEL FDC for 12 weeks	Drug: SOF/VEL; 400/100 mg tablet administered orally once daily; Other Names: Epclusa® GS-7977/GS-5816

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.

2. Percentage of Participants Who Prematurely Discontinued Study Drug Due to Any Adverse Event [Up to 12 weeks]

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 4 Weeks After Cessation of Therapy (SVR4) [Posttreatment Week 4]

   SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

2. Percentage of Participants With HCV RNA < LLOQ at Week 2 [Week 2]

3. Percentage of Participants With HCV RNA < LLOQ at Week 4 [Week 4]

4. Percentage of Participants With HCV RNA < LLOQ at Week 8 [Week 8]

5. Percentage of Participants With HCV RNA < LLOQ at Week 12 [Week 12]

6. HCV RNA at Week 2 [Week 2]

7. HCV RNA at Week 4 [Week 4]

8. HCV RNA at Week 8 [Week 8]

9. HCV RNA at Week 12 [Week 12]

10. Change From Baseline in HCV RNA at Week 2 [Baseline; Week 2]

11. Change From Baseline in HCV RNA at Week 4 [Baseline; Week 4]

12. Change From Baseline in HCV RNA at Week 8 [Baseline; Week 8]

13. Change From Baseline in HCV RNA at Week 12 [Baseline; Week 12]

14. Percentage of Participants With Virologic Failure [Up to Posttreatment Week 12]

    Virologic failure was defined as On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ on 2 consecutive measurements while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 12 weeks of treatment) Virologic relapse: HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• History of chronic HCV infection (≥ 6 months)

• HCV genotype 1, 2, 3, 4, 5, 6, or indeterminate

• Liver transplant ≥ 3 months prior to screening

• Male and nonpregnant/ non-lactating female individuals without cirrhosis or with compensated cirrhosis

Key Exclusion Criteria:

• History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol,

• Co-infection with HIV or hepatitis B virus

• Known hypersensitivity to study medication,

• Use of any prohibited concomitant medications as within with window before the Day 1 visit.

• De novo or recurrent hepatocellular carcinoma posttransplant

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clínic de Barcelona	Barcelona		Spain
2	Hospital Universitari Vall d'Hebron	Barcelona		Spain
3	Reina Sofía University Hospital	Córdoba		Spain
4	Hospital General Universitario Gregorio Maranon	Madrid		Spain
5	Hospital Ramón Y Cajal	Madrid		Spain
6	Hospital Universitario Virgen del Rocío	Sevilla		Spain
7	La Fe Hospital	Valencia		Spain
8	Hospital Clinico Zaragoza	Zaragoza		Spain
9	Universität Bern	Bern		Switzerland
10	University Hospital Zurich	Zürich		Switzerland
11	Cambridge University Hospitals NHS Foundation Trust	Cambridge		United Kingdom
12	Royal Infirmary of Edinburgh	Edinburgh		United Kingdom
13	St James University Hospital	Leeds		United Kingdom
14	Kings College Hospital	London		United Kingdom
15	Royal Free Hampstead NHS Trust	London		United Kingdom

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Feb 19, 2016
• Statistical Analysis Plan - Aug 10, 2017

More Information

Publications

• Agarwal K, Castells L, Müllhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Mariño Z, Dufour JF, Forns X. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol. 2018 Sep;69(3):603-607. doi: 10.1016/j.jhep.2018.05.039. Epub 2018 Jun 8.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02781571
• Other Study ID Numbers: GS-US-342-2104; 2016-000416-15
• First Posted: May 24, 2016
• Last Update Posted: Nov 14, 2018
• Last Verified: Jul 1, 2018

• 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; Virus Diseases; Hepatitis; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Spain, Switzerland, and the United Kingdom. The first participant was screened on 27 July 2016. The last study visit occurred on 28 July 2017.
Pre-assignment Detail	85 participants were screened.

Arm/Group Title	SOF/VEL
Arm/Group Description	Sofosbuvir/Velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Period Title: Overall Study
STARTED	79
COMPLETED	79
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Overall Participants	79
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62 (8.7)
Sex: Female, Male (Count of Participants)
Female	15 19%
Male	64 81%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.5%
Not Hispanic or Latino	77 97.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 15.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.5%
White	65 82.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	41 51.9%
Switzerland	7 8.9%
Spain	31 39.2%
IL28b Status (Count of Participants)
CC	39 49.4%
CT	34 43%
TT	6 7.6%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.4 (0.55)
HCV RNA Category (Count of Participants)
< 800,000 IU/mL	18 22.8%
≥ 800,000 IU/mL	61 77.2%
HCV genotype (Count of Participants)
Genotype 1	37 46.8%
Genotype 2	3 3.8%
Genotype 3	35 44.3%
Genotype 4	4 5.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all enrolled participants who took at least 1 dose of the study drug

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	79
Number (95% Confidence Interval) [percentage of participants]	96.2 121.8%

2. Primary Outcome

Title	Percentage of Participants Who Prematurely Discontinued Study Drug Due to Any Adverse Event
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who took at least 1 dose if the study drug.

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	79
Number [percentage of participants]	1.3 1.6%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 4 Weeks After Cessation of Therapy (SVR4)
Description	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	79
Number (95% Confidence Interval) [Percentage of participants]	97.5 123.4%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 2
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	79
Number (95% Confidence Interval) [percentage of participants]	40.5 51.3%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 4
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Number (95% Confidence Interval) [percentage of participants]	85.9 108.7%

6. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 8
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Number (95% Confidence Interval) [percentage of participants]	98.7 124.9%

7. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 12
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Number (95% Confidence Interval) [percentage of participants]	100.0 126.6%

8. Secondary Outcome

Title	HCV RNA at Week 2
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	75
Mean (Standard Deviation) [log10 IU/mL]	1.59 (0.596)

9. Secondary Outcome

Title	HCV RNA at Week 4
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Mean (Standard Deviation) [log10 IU/mL]	1.23 (0.251)

10. Secondary Outcome

Title	HCV RNA at Week 8
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	77
Mean (Standard Deviation) [log10 IU/mL]	1.15 (0.00)

11. Secondary Outcome

Title	HCV RNA at Week 12
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Mean (Standard Deviation) [log10 IU/mL]	1.15 (0.00)

12. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 2
Time Frame	Baseline; Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	75
Mean (Standard Deviation) [log10 IU/mL]	-4.75 (0.635)

13. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 4
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Mean (Standard Deviation) [log10 IU/mL]	-5.13 (0.551)

14. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 8
Time Frame	Baseline; Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	77
Mean (Standard Deviation) [log10 IU/mL]	-5.20 (0.548)

15. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 12
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	78
Mean (Standard Deviation) [log10 IU/mL]	-5.22 (0.554)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
Measure Participants	79
Number [percentage of participants]	2.5 3.2%

Adverse Events

Time Frame	Up to 12 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants who took at least 1 dose of the study drug.
Arm/Group Title	SOF/VEL
Arm/Group Description	SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks in participants with chronic HCV infection who received a liver transplant
All Cause Mortality
	SOF/VEL
	Affected / at Risk (%)	# Events
Total	0/79 (0%)
Serious Adverse Events
	SOF/VEL
	Affected / at Risk (%)	# Events
Total	3/79 (3.8%)
Infections and infestations
Pneumonia klebsiella	1/79 (1.3%)
Musculoskeletal and connective tissue disorders
Joint swelling	1/79 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	1/79 (1.3%)
Other (Not Including Serious) Adverse Events
	SOF/VEL
	Affected / at Risk (%)	# Events
Total	42/79 (53.2%)
Gastrointestinal disorders
Diarrhoea	6/79 (7.6%)
Nausea	6/79 (7.6%)
General disorders
Asthenia	5/79 (6.3%)
Fatigue	16/79 (20.3%)
Infections and infestations
Influenza	5/79 (6.3%)
Viral upper respiratory tract infection	5/79 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	4/79 (5.1%)
Musculoskeletal and connective tissue disorders
Myalgia	4/79 (5.1%)
Nervous system disorders
Headache	19/79 (24.1%)
Respiratory, thoracic and mediastinal disorders
Cough	8/79 (10.1%)

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