Efficacy and Safety of Sofosbuvir Plus Ribavirin in Japanese Adults With Chronic Genotype 2 HCV Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01910636
• Collaborator: (none)
• Enrollment: 153
• Locations: 19
• Arm: 1
• Duration (Months): 15.9
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus ribavirin (RBV) in Japanese participants with chronic genotype 2 hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Sofosbuvir; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: N/A
• Intervention Model: Single Group 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 Plus Ribavirin in Treatment-Naïve and Treatment-Experienced Japanese Subjects With Chronic Genotype 2 HCV Infection
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sofosbuvir+RBV 12 weeks Participants will receive sofosbuvir+RBV for 12 weeks.	Drug: Sofosbuvir; Sofosbuvir 400 mg tablet administered orally once daily; Other Names: GS-7977 PSI-7977 Sovaldi® ; Drug: RBV; Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing according to the approved Copegus labeling in Japan (< 60 kg = 600 mg , > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg); Other Names: Copegus®

Outcome Measures

Primary Outcome Measures

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

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.

2. Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [Up to 12 weeks]

   The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]

   SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.

2. Percentage of Participants Experiencing Viral Breakthrough [Up to 12 weeks]

   Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values.

3. Percentage of Participants Experiencing Viral Relapse [Up to Posttreatment Week 24]

   Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic genotype 2 HCV-infection

• Male or female, age ≥ 20 years

• Body weight ≥ 40 kg

• HCV RNA ≥ 10,000 IU/mL at screening

Exclusion Criteria:

• Current or prior history of clinically significant illness other than HCV

• Pregnant or nursing female or male with pregnant female partner

• Chronic liver disease of a non-HCV etiology

• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Akita		Japan
2		Chiba		Japan
3		Chiyoda-ku		Japan
4		Gifu		Japan
5		Ichikawa		Japan
6		Itabashi-ku		Japan
7		Izunokuni		Japan
8		Kita-Ku		Japan
9		Kurashiki		Japan
10		Kurume		Japan
11		Matsumoto		Japan
12		Musashino		Japan
13		Nishinomiya		Japan
14		Ogaki		Japan
15		Omura		Japan
16		Sapporo		Japan
17		Shinjuku-ku		Japan
18		Suita		Japan
19		Yamagata		Japan

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Steven Knox, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01910636
• Other Study ID Numbers: GS-US-334-0118
• First Posted: Jul 29, 2013
• Last Update Posted: Mar 24, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Gilead Sciences: HCV genotype 2 (GT-2)
• Additional relevant MeSH terms: Hepatitis C; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 20 study sites in Japan. The first participant was screened on 28 June 2013. The last study visit occurred on 09 June 2014.
Pre-assignment Detail	188 participants were screened.

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced
Arm/Group Description	Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)
Period Title: Overall Study
STARTED	90	63
COMPLETED	90	63
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced	Total
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)	Total of all reporting groups
Overall Participants	90	63	153
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (10.6)	60 (8.8)	57 (10.1)
Sex: Female, Male (Count of Participants)
Female	57 63.3%	26 41.3%	83 54.2%
Male	33 36.7%	37 58.7%	70 45.8%
Cirrhosis Status (participants) [Number]
No	82 91.1%	54 85.7%	136 88.9%
Yes	8 8.9%	9 14.3%	17 11.1%
IL28b Status (participants) [Number]
CC	73 81.1%	48 76.2%	121 79.1%
CT	17 18.9%	11 17.5%	28 18.3%
TT	0 0%	4 6.3%	4 2.6%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.2 (0.92)	6.5 (0.66)	6.3 (0.84)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	26 28.9%	12 19%	38 24.8%
≥ 800,000 IU/mL	64 71.1%	51 81%	115 75.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who were enrolled, received at least 1 dose of study drug, and had chronic genotype 2 HCV infection.

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)
Measure Participants	90	63
Number [percentage of participants]	97.8 108.7%	95.2 151.1%

2. Primary Outcome

Title	Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
Description	The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug

Arm/Group Title	SOF+RBV
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks
Measure Participants	153
Number [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description	SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame	Posttreatment Weeks 4 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)
Measure Participants	90	63
SVR4	98.9 109.9%	95.2 151.1%
SVR24	97.8 108.7%	95.2 151.1%

4. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Breakthrough
Description	Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)
Measure Participants	90	63
Number [percentage of participants]	0 0%	0 0%

5. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Relapse
Description	Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF+RBV Treatment Naive	SOF+RBV Treatment Experienced
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment naive)	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks (treatment experienced)
Measure Participants	90	63
Number [percentage of participants]	2.2 2.4%	4.8 7.6%

Adverse Events

Time Frame	Up to 12 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	SOF+RBV
Arm/Group Description	SOF 400 mg tablet once daily + RBV tablets (600-1000 mg daily based on weight) for 12 weeks
All Cause Mortality
	SOF+RBV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SOF+RBV
	Affected / at Risk (%)	# Events
Total	2/153 (1.3%)
Blood and lymphatic system disorders
Anaemia	1/153 (0.7%)
Immune system disorders
Allergy to arthropod sting	1/153 (0.7%)
Other (Not Including Serious) Adverse Events
	SOF+RBV
	Affected / at Risk (%)	# Events
Total	69/153 (45.1%)
Blood and lymphatic system disorders
Anaemia	18/153 (11.8%)
General disorders
Malaise	11/153 (7.2%)
Infections and infestations
Nasopharyngitis	45/153 (29.4%)
Nervous system disorders
Headache	15/153 (9.8%)
Skin and subcutaneous tissue disorders
Pruritus	9/153 (5.9%)

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