FISSION: Phase 3 Study of Sofosbuvir and Ribavirin

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01497366
• Collaborator: (none)
• Enrollment: 527
• Locations: 97
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study was to assess the safety and efficacy of sofosbuvir (GS-7977; PSI-7977) in combination with ribavirin (RBV) administered for 12 weeks compared with pegylated interferon (PEG)/RBV administered for 24 weeks in treatment-naive patients with Hepatitis C (HCV) genotype 2 or 3. Efficacy was assessed by the rate of sustained viral response (SVR) 12 weeks after the discontinuation of therapy (SVR12). This was a non-inferiority study, and if non-inferiority was demonstrated, the study was then allowed to test for superiority.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 527 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Active-Controlled Study to Investigate the Safety and Efficacy of PSI-7977 and Ribavirin for 12 Weeks Compared to Pegylated Interferon and Ribavirin for 24 Weeks in Treatment-Naïve Patients With Chronic Genotype 2 or 3 HCV Infection
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sofosbuvir+RBV Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: Sovaldi™ GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg Dose of PEG+RBV group: 800 mg
Active Comparator: PEG+RBV Participants were randomized to receive PEG+RBV for 24 weeks.	Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys® ; Drug: RBV; Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg Dose of PEG+RBV group: 800 mg

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Stopping All Study Drugs (SVR12) [Post-treatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; < 25 IU/mL) 12 weeks after study drug cessation.

Secondary Outcome Measures

1. Number of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities [Up to 24 weeks plus 30 days following the last dose of study drug]

2. Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24) [Post-treatment Week 24]

   SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation.

3. Percentage of Participants With HCV RNA < LLOQ on Treatment [Up to 12 Weeks]

4. Change From Baseline in HCV RNA [Baseline to Week 12]

5. Percentage of Participants With Virologic Failure During Treatment [Baseline up to Week 24]

   Virologic failure was defined as either Viral breakthrough: HCV RNA ≥ 25 IU/mL after having previously had HCV RNA < 25 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement Non-response: HCV RNA persistently ≥ 25 IU/ml while on treatment (through Week 12)

6. Percentage of Participants With Viral Relapse Following Treatment [Up to Post-treatment Week 24]

   Viral relapse was defined as HCV RNA ≥ 25 IU/mL in post-treatment after having achieved < LLOQ at last on-treatment measurement, confirmed with 2 consecutive values or last available measurement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chronic Genotype 2 or 3 HCV-infection

• Naive to all HCV antiviral treatment(s)

Exclusion Criteria:

• Positive test at Screening for HBsAg, anti-hepatitis B core immunoglobulin M antibody (anti-HBc IgM Ab), or anti-HIV Ab

• History of any other clinically significant chronic liver disease

• A history consistent with decompensated liver disease

• History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or a history of malignancy, that makes the subject unsuitable for the study.

• Participation in a clinical study within 3 months prior to first dose

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Alabama Liver & Digestive Specialist	Montgomery	Alabama	United States	36116
3	Franco Felizarta, MD	Bakersfield	California	United States	93301
4	California Liver Institute	Beverly Hills	California	United States	90210
5	Arrowhead Regional Medical Center	Colton	California	United States	92324
6	SCTI Research Foundation	Coronado	California	United States	92118
7	eStudy Site	La Mesa	California	United States	91940
8	Peter J. Ruane, M.D. Inc.	Los Angeles	California	United States	90036
9	eStudySite	Oceanside	California	United States	92056
10	University of California, Davis - Health System	Sacramento	California	United States	95817
11	University of California San Diego Medical Center	San Diego	California	United States	92103
12	Research and Education, Inc.	San Diego	California	United States	92105
13	Medical Associates Research Group, Inc.	San Diego	California	United States	92123
14	Quest Clinical Research	San Francisco	California	United States	94115
15	South Denver Gastroenterology, PC	Englewood	Colorado	United States	80113
16	Pointe West Infectious Diseases	Bradenton	Florida	United States	34209
17	Midway Immunology & Research Center, LLC	Fort Pierce	Florida	United States	34982
18	University of Florida College of Medicine	Gainesville	Florida	United States	32610
19	Borland-Groover Clinic Baptist	Jacksonville	Florida	United States	32256
20	University of Miami, School of Medicine	Miami	Florida	United States	33136
21	Orlando Immunology Center	Orlando	Florida	United States	32803
22	Internal Medicine Specialists	Orlando	Florida	United States	32806
23	Advanced Research Institute	Trinity	Florida	United States	34655
24	South Florida Center of Gastroenterology	Wellington	Florida	United States	33414
25	AIDS Research Consortium of Atlanta, Inc.	Atlanta	Georgia	United States	30308
26	Atlanta Gastroenterology Associates	Atlanta	Georgia	United States	30308
27	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia	United States	30060
28	University of Chicago	Chicago	Illinois	United States	60637
29	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana	United States	46237
30	Digestive Disease Associates, P.A.	Baltimore	Maryland	United States	21229
31	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
32	The Research Institute	Springfield	Massachusetts	United States	01105
33	Partners in Internal Medicine, PC	Worcester	Massachusetts	United States	01608-1320
34	University of Massachusetts, Worcester	Worcester	Massachusetts	United States	01655
35	Henry Ford Health System	Detroit	Michigan	United States	48202
36	Digestive Health Specialists, PA	Tupelo	Mississippi	United States	38801
37	Veterans Affairs Medical Center	East Orange	New Jersey	United States	07018
38	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey	United States	08234
39	ID Care	Hillsborough	New Jersey	United States	08844
40	Atlantic Research Affiliates, LLC	Morristown	New Jersey	United States	07960
41	Southwest C.A.R.E. Center	Santa Fe	New Mexico	United States	87505
42	North Shore University Hospital	Manhasset	New York	United States	11030
43	Weill Cornell Medical College	New York	New York	United States	10021
44	Mount Sinai School of Medicine	New York	New York	United States	10029
45	University of Rochester	Rochester	New York	United States	14662
46	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina	United States	28801
47	Duke University Medical Center	Durham	North Carolina	United States	27710
48	Carolinas Center for Liver Disease	Statesville	North Carolina	United States	28677
49	Digestive Health Specialists, PA	Winston-Salem	North Carolina	United States	27103
50	University of Cincinnati	Cincinnati	Ohio	United States	45267
51	Gastroenterology United of Tulsa	Tulsa	Oklahoma	United States	74135
52	Schleinitz Research and Gastroenterology LLC	Medford	Oregon	United States	97504
53	Regional Gastroenterology Associates of Lancaster, Ltd.	Lancaster	Pennsylvania	United States	17604
54	UPMC Center For Liver Diseases	Pittsburgh	Pennsylvania	United States	15213
55	University Gastroenterology	Warwick	Rhode Island	United States	02886
56	Gastro One	Germantown	Tennessee	United States	38138
57	Nashville Gastrointestinal Specialists Inc.	Nashville	Tennessee	United States	37211
58	Texas Clinical Research Institute, LLC	Arlington	Texas	United States	76012
59	Baylor University Medical Center	Dallas	Texas	United States	75246
60	Kelsey-Seybold Clinic PA	Houston	Texas	United States	77005
61	Research Specialists of Texas	Houston	Texas	United States	77030
62	VAMC & Baylor College	Houston	Texas	United States	77030
63	Alamo Medical Research	San Antonio	Texas	United States	78215
64	Metropolitan Research	Fairfax	Virginia	United States	22031
65	Digestive and Liver Disease Specialist, Ltd.	Norfolk	Virginia	United States	23502
66	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
67	Virginia Mason Medical Center	Seattle	Washington	United States	98101
68	Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
69	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
70	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2137
71	St. George Hospital	Kogarah	New South Wales	Australia	2217
72	Gallipoli MRF	Greenslopes	Queensland	Australia	4120
73	Royal Brisbane Hospital Research Foundation	Herston	Queensland	Australia	4029
74	Princess Alexandria	Woollongabba	Queensland	Australia	4102
75	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
76	Monash Medical Centre	Clayton	Victoria	Australia	3168
77	Austin Hospital	Heidelberg	Victoria	Australia	3084
78	The Alfred	Melbourne	Victoria	Australia	3004
79	Fremantle Hospital	Fremantle	Western Australia	Australia	6160
80	Sir Charles Gairdner	Nedlands	Western Australia	Australia	6009
81	Royal Perth Hospital	Perth	Western Australia	Australia	6000
82	(G.I.R.I.) Gastrointestinal Research Institute	Vancouver	British Columbia	Canada	V6Z 2K5
83	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
84	University Health Network-Toronto Western Hospital	Toronto	Ontario	Canada	M5G 2N2
85	Toronto Liver Centre	Toronto	Ontario	Canada	M6H 3M1
86	Toronto Digestive Disease Associates, Inc.	Vaughan	Ontario	Canada	L4L 4Y7
87	Casa Sollievo della Sofferenza Hospital	San Giovanni Rotondo		Italy	71013
88	Academish Medisch Centrum	Amsterdam		Netherlands	1105 AZ
89	Auckland City Hospital	Grafton	Auckland	New Zealand
90	Tauranga Hospital	Tauranga	BOP	New Zealand	3143
91	Christchurch Hospital	Chrischurch	Canterbury	New Zealand	8001
92	Mercy Hospital	Dunedin	OTA	New Zealand	9010
93	Waikato Hospital (District Health Board)	Hamilton	Waikato	New Zealand	3240
94	Wellington Hospital	Newtown	WGN	New Zealand	6021
95	Fundacion de Investigacion de Diego	San Juan		Puerto Rico	00927
96	Sahlgrenska Universitetssjukhuset, Östra Sjukhus	Göteborg		Sweden	41685
97	Karolinska Universitetssjukhuset, Solna	Stockholm		Sweden	171 76

Sponsors and Collaborators

• Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01497366
• Other Study ID Numbers: P7977-1231
• First Posted: Dec 22, 2011
• Last Update Posted: Apr 2, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Gilead Sciences: HCV genotype 2 (GT-2); HCV genotype 3 (GT-3)
• Additional relevant MeSH terms: Hepatitis C; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled in a total of 90 study sites in the United States, Australia, New Zealand, Canada, Sweden, Italy, and the Netherlands. The first participant was screened on 19 December 2011. The last participant observation was on 08 April 2013.
Pre-assignment Detail	666 participants were screened and 527 were randomized; 499 participants received at least 1 dose of study drug, and comprise the Safety Analysis Set. The 496 participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug comprise the Full Analysis Set.

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+ribavirin (RBV) for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Period Title: Overall Study
STARTED	263	264
Randomized But Not Treated	7	21
COMPLETED	224	176
NOT COMPLETED	39	88

Baseline Characteristics

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV	Total
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.	Total of all reporting groups
Overall Participants	256	243	499
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (10.8)	48 (11.4)	48 (11.0)
Sex: Female, Male (Count of Participants)
Female	85 33.2%	87 35.8%	172 34.5%
Male	171 66.8%	156 64.2%	327 65.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	41 16%	31 12.8%	72 14.4%
Not Hispanic or Latino	215 84%	212 87.2%	427 85.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	12 4.7%	5 2.1%	17 3.4%
White	223 87.1%	212 87.2%	435 87.2%
Asian	14 5.5%	15 6.2%	29 5.8%
American Indian/Alaska Native/First Nations	4 1.6%	4 1.6%	8 1.6%
Hawaiian or Pacific Islander	2 0.8%	6 2.5%	8 1.6%
Black and White	1 0.4%	0 0%	1 0.2%
South American	0 0%	1 0.4%	1 0.2%
Region of Enrollment (participants) [Number]
United States	165 64.5%	151 62.1%	316 63.3%
Canada	15 5.9%	24 9.9%	39 7.8%
Australia	32 12.5%	29 11.9%	61 12.2%
Netherlands	3 1.2%	1 0.4%	4 0.8%
Italy	8 3.1%	4 1.6%	12 2.4%
New Zealand	29 11.3%	30 12.3%	59 11.8%
Sweden	4 1.6%	4 1.6%	8 1.6%
Hepatitis C Virus (HCV) genotype (participants) [Number]
Genotype 1	3 1.2%	0 0%	3 0.6%
Genotype 2	70 27.3%	67 27.6%	137 27.5%
Genotype 3	183 71.5%	176 72.4%	359 71.9%
Baseline HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.0 (0.82)	6.0 (0.78)	6.0 (0.80)
Baseline HCV RNA Category (participants) [Number]
< 6 log10 IU/mL	108 42.2%	106 43.6%	214 42.9%
≥ 6 log10 IU/mL	148 57.8%	137 56.4%	285 57.1%
IL28b genotype (participants) [Number]
CC	108 42.2%	106 43.6%	214 42.9%
CT	121 47.3%	98 40.3%	219 43.9%
TT	25 9.8%	38 15.6%	63 12.6%
Missing	2 0.8%	1 0.4%	3 0.6%
Cirrhosis (participants) [Number]
No	205 80.1%	189 77.8%	394 79%
Yes	50 19.5%	50 20.6%	100 20%
Missing	1 0.4%	4 1.6%	5 1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Stopping All Study Drugs (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; < 25 IU/mL) 12 weeks after study drug cessation.
Time Frame	Post-treatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	253	243
Number [percentage of participants]	67 26.2%	67 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sofosbuvir+RBV, PEG+RBV
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority would be demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the difference in SVR12 rates was greater than -15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -7.5 to 8.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in percentages between treatment groups and the 95% CI calculated were based on stratum adjusted Mantel-Haenszel proportions.

2. Secondary Outcome

Title	Number of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Time Frame	Up to 24 weeks plus 30 days following the last dose of study drug

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	256	243
AEs leading to discontinuation of any study drug	3 1.2%	29 11.9%
Serious AEs	7 2.7%	3 1.2%
Grade 3 laboratory abnormalities	33 12.9%	80 32.9%
Grade 4 laboratory abnormalities	3 1.2%	21 8.6%
Deaths	1 0.4%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24)
Description	SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation.
Time Frame	Post-treatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	253	243
Number [percentage of participants]	66.8 26.1%	65.4 26.9%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ on Treatment
Time Frame	Up to 12 Weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir (SOF)+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	253	243
Week 1 (SOF+RBV, n = 252; PEG+RBV, n = 243)	43.7 17.1%	6.6 2.7%
Week 2 (SOF+RBV, n = 251; PEG+RBV, n = 241)	92.0 35.9%	31.5 13%
Week 4 (SOF+RBV, n = 250; PEG+RBV, n = 236)	99.6 38.9%	66.9 27.5%
Week 8 (SOF+RBV, n = 248; PEG+RBV, n = 231)	99.6 38.9%	85.7 35.3%
Week 12 (SOF+RBV, n = 244; PEG+RBV, n = 224)	99.2 38.8%	92.4 38%

5. Secondary Outcome

Title	Change From Baseline in HCV RNA
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir (SOF)+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	253	243
Week 1 (SOF+RBV, n = 239; PEG+RBV, n = 236)	-4.26 (0.689)	-2.19 (1.287)
Week 2 (SOF+RBV, n = 246; PEG+RBV, n = 233)	-4.60 (0.820)	-3.19 (1.572)
Week 4 (SOF+RBV, n = 250; PEG+RBV, n = 235)	-4.64 (0.816)	-4.04 (1.389)
Week 8 (SOF+RBV, n = 248; PEG+RBV, n = 228)	-4.63 (0.850)	-4.42 (1.163)
Week 12 (SOF+RBV, n = 243; PEG+RBV, n = 222)	-4.65 (0.820)	-4.45 (1.226)

6. Secondary Outcome

Title	Percentage of Participants With Virologic Failure During Treatment
Description	Virologic failure was defined as either Viral breakthrough: HCV RNA ≥ 25 IU/mL after having previously had HCV RNA < 25 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement Non-response: HCV RNA persistently ≥ 25 IU/ml while on treatment (through Week 12)
Time Frame	Baseline up to Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	253	243
Number [percentage of participants]	0.4 0.2%	7.4 3%

7. Secondary Outcome

Title	Percentage of Participants With Viral Relapse Following Treatment
Description	Viral relapse was defined as HCV RNA ≥ 25 IU/mL in post-treatment after having achieved < LLOQ at last on-treatment measurement, confirmed with 2 consecutive values or last available measurement.
Time Frame	Up to Post-treatment Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sofosbuvir+RBV	PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.	Participants were randomized to receive PEG+RBV for 24 weeks.
Measure Participants	249	217
Number [percentage of participants]	30.5 11.9%	22.6 9.3%

Adverse Events

Time Frame	Up to 24 weeks plus 30 days following the last dose of study drug
Arm/Group Title	Sofosbuvir+RBV		PEG+RBV
Arm/Group Description	Participants were randomized to receive sofosbuvir+RBV for 12 weeks.		Participants were randomized to receive PEG+RBV for 24 weeks.
All Cause Mortality
	Sofosbuvir+RBV		PEG+RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sofosbuvir+RBV		PEG+RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/256 (2.7%)		3/243 (1.2%)
Blood and lymphatic system disorders
Anaemia	1/256 (0.4%)		0/243 (0%)
Cardiac disorders
Atrioventriclar shock	0/256 (0%)		1/243 (0.4%)
General disorders
Chest pain	1/256 (0.4%)		0/243 (0%)
Immune system disorders
Allergy to arthropod sting	1/256 (0.4%)		0/243 (0%)
Infections and infestations
Cellulitis	1/256 (0.4%)		0/243 (0%)
Infection	0/256 (0%)		1/243 (0.4%)
Osteomyelitis chronic	1/256 (0.4%)		0/243 (0%)
Urinary tract infection	1/256 (0.4%)		0/243 (0%)
Injury, poisoning and procedural complications
Clavicle fracture	0/256 (0%)		1/243 (0.4%)
Rib fracture	0/256 (0%)		1/243 (0.4%)
Toxicity to various agents	1/256 (0.4%)		0/243 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ	0/256 (0%)		1/243 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/256 (0.4%)		0/243 (0%)
Pneumothorax	0/256 (0%)		1/243 (0.4%)
Other (Not Including Serious) Adverse Events
	Sofosbuvir+RBV		PEG+RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	219/256 (85.5%)		233/243 (95.9%)
Blood and lymphatic system disorders
Anaemia	20/256 (7.8%)		28/243 (11.5%)
Neutropenia	0/256 (0%)		30/243 (12.3%)
Thrombocytopenia	0/256 (0%)		23/243 (9.5%)
Gastrointestinal disorders
Nausea	46/256 (18%)		70/243 (28.8%)
Diarrhoea	23/256 (9%)		42/243 (17.3%)
Vomiting	17/256 (6.6%)		23/243 (9.5%)
Dry mouth	10/256 (3.9%)		15/243 (6.2%)
General disorders
Fatigue	92/256 (35.9%)		134/243 (55.1%)
Irritability	25/256 (9.8%)		40/243 (16.5%)
Chills	7/256 (2.7%)		44/243 (18.1%)
Influenza like illness	7/256 (2.7%)		44/243 (18.1%)
Pyrexia	6/256 (2.3%)		33/243 (13.6%)
Pain	5/256 (2%)		30/243 (12.3%)
Injection site reaction	0/256 (0%)		17/243 (7%)
Injection site erythema	0/256 (0%)		14/243 (5.8%)
Infections and infestations
Nasopharyngitis	13/256 (5.1%)		5/243 (2.1%)
Metabolism and nutrition disorders
Decreased appetite	17/256 (6.6%)		44/243 (18.1%)
Musculoskeletal and connective tissue disorders
Myalgia	21/256 (8.2%)		40/243 (16.5%)
Arthralgia	15/256 (5.9%)		35/243 (14.4%)
Back pain	9/256 (3.5%)		20/243 (8.2%)
Nervous system disorders
Headache	64/256 (25%)		108/243 (44.4%)
Dizziness	27/256 (10.5%)		33/243 (13.6%)
Psychiatric disorders
Insomnia	31/256 (12.1%)		71/243 (29.2%)
Depression	14/256 (5.5%)		35/243 (14.4%)
Anxiety	11/256 (4.3%)		16/243 (6.6%)
Respiratory, thoracic and mediastinal disorders
Cough	19/256 (7.4%)		21/243 (8.6%)
Dyspnoea	18/256 (7%)		20/243 (8.2%)
Oropharyngeal pain	14/256 (5.5%)		10/243 (4.1%)
Skin and subcutaneous tissue disorders
Rash	23/256 (9%)		43/243 (17.7%)
Pruritus	19/256 (7.4%)		42/243 (17.3%)
Alopecia	12/256 (4.7%)		24/243 (9.9%)
Dry skin	11/256 (4.3%)		23/243 (9.5%)

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