Sofosbuvir and Ribavirin in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01682720
• Collaborator: (none)
• Enrollment: 421
• Locations: 77
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability, and antiviral efficacy of GS-7977 with ribavirin (RBV) in participants with genotype 2 or 3 hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: SOF; Drug: RBV; Drug: Placebo to match SOF; Drug: Placebo to match RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 421 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GS-7977+Ribavirin for 12 Weeks in Treatment Naive and Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection.
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 12 Weeks (GT2/3) Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.	Drug: Placebo to match SOF; Placebo to match SOF administered orally once daily; Drug: Placebo to match RBV; Placebo to match RBV administered orally in a divided daily dose
Experimental: SOF 12 Weeks (GT2/3) Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: SOF 24 Weeks (GT3) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet administered orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 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) 12 weeks following the last dose of study drug. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.

2. Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [Up to 24 weeks]

   The percentage of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was analyzed.

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 SVR24 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.

2. Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse [Up to Posttreatment Week 24]

   Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment. Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age > 18 with chronic genotype 2 or 3 HCV infection

• HCV RNA > 10,000 IU/mL at screening

• Subjects must be treatment naive or treatment experienced

• Presence or absence of cirrhosis; a liver biopsy may be required

• Healthy according to medical history and physical examination with the exception of HCV diagnosis

• Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication

Exclusion Criteria:

• Prior use of any other inhibitor of the HCV NS5B Polymerase

• History of any other clinically significant chronic liver disease

• Evidence of or history of decompensated liver disease

• HIV or chronic hepatitis B virus (HBV) infection

• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)

• Chronic use of immunosuppressive agents or immunomodulatory agents

• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Universitat Graz	Graz		Austria	A-8036
2	Medizinische Universitat Wien	Wien		Austria	1090
3	Wilhelminenspital	Wien		Austria	1160
4	West Tallinn Central Hospital	Tallin		Estonia	10617
5	Tartu University Hospital	Tartu		Estonia	51014
6	CHRU de Lille, Hopital Claude Huriez	CHRU Lille		France	59037
7	CHU Estaing	Clermont Ferrand		France	63003
8	Hopital Beaujon	Clichy Cedex		France	92110
9	Hopital Henri Mondor	Creteil Cedex		France	94000
10	Département Hépatogastroentérologie - CHU de Grenoble	Grenoble		France	38043
11	Hopital Saint Joseph	Marseille, Cedex 8		France	13008
12	Hopital Saint Eloi	Montpellier		France	34295
13	Hopital de l Archet 2	Nice		France	6202
14	Hopitaux Universitaires	Paris, Cedex 14		France	75679
15	Hopital Saint Antoine	Paris		France	75012
16	Hopital Pitie Salpetriere	Paris		France	75013
17	Groupe Hospitalier Sud - Hôpital Haut-Lévêque - USN	Pessac		France	33604
18	CHU Pontchaillou - Hématologie Clinique	Rennes Cedex 9		France	35033
19	Centre Hospitalier Universitaire de Strasbourg	Strasbourg		France	67091
20	CHU de Nancy, Hôpital de Brabois	Vandoeuvre les Nancy		France	54511
21	Praxiszentrum	Freiburg	Baden Wuerttemberg	Germany	79098
22	Leber- and Studienzentrum am Checkpoint	Berlin		Germany	10969
23	Universitaetsklinikum Bonn	Bonn		Germany	53125
24	Heinrich Heine Unversitat	Dusseldorf		Germany	40225
25	JWG-Universität Frankfurt	Frankfurt am Main		Germany	60590
26	Asklepios Klinik Sankt Georg H	Hamburg		Germany	20099
27	Universitatsklinikum	Hamburg		Germany	20246
28	Medizinische Hochschule Hannov	Hannover		Germany	30625
29	Medizinische Klinik IV, Dep. o	Heidelberg		Germany	69120
30	Gastroenterologische Gemeinsch	Herne		Germany	44623
31	Leberstudienzentrum Kiel	Kiel		Germany	24146
32	Universitaetsklinikum Leipzig	Leipzig		Germany	4103
33	Klinikum der Universität Münch	Munchen		Germany	81377
34	Centrum fuer interdisziplinaere Medizin Muenster GmbH	Münster		Germany	D-48143
35	Ospedale Casa Sollievo	San Giovanni Rotondo	Foggia	Italy	71013
36	Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi	Bologna		Italy	40138
37	Ospedale S. Annunziata	Florence		Italy	50011
38	Ente Ospedaliero Ospedali Galliera	Genova		Italy	16128
39	Fondazione IRCCS CA Granada - Ospedale Maggiore Policlinico	Milano		Italy	20122
40	Azienda Ospedaliera Ospedale Niguarda Cà Granda	Milano		Italy	20162
41	University of Padova	Padova		Italy	35100
42	University of Palermo	Palermo		Italy	90127
43	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43100
44	Fondazione PTV - Policlinico Tor Vergata	Roma		Italy	133
45	INMI "Lazzaro Spallanzani" I.R.C.C.S.	Roma		Italy	149
46	Azienda Ospedaliera Universitaria San Giovanni Battista di Torino	Torino		Italy	10126
47	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
48	Leids Universitair Medisch Centrum	Leiden		Netherlands	2300 RC
49	UMC St. Radboud - Gastroenterology	Nijmegen		Netherlands	6500 HB
50	Erasmus MC	Rotterdam		Netherlands	3015 CE
51	Wojewodzki Szpital Specjalistyczny im Dluskeigo	Bialystok		Poland	15-540
52	Wojewodzki Specjalistyczny Szpital im. W. Bieganskiego	Lodz		Poland	91-347
53	SP ZOZ Wojewodzki Szpital Zakazny w Warszawie	Warszawa		Poland	01-201
54	NZOZ Centrum Badan Klinicznych	Wroclaw		Poland	50-349
55	Hospital Universitari Vall d'H	Barcelona		Spain	08035
56	Hospital Casa de la Maternidad	Barcelona		Spain	08036
57	Hospital Carlos III	Madrid		Spain	28029
58	Hospital Universitario La Paz	Madrid		Spain	28046
59	Hospital Puerta de Hierro Maja	Majadahonda		Spain	28222
60	Complejo Hospitalario de Especialidades Virgen de la Victoria	Malaga		Spain	29071
61	Hospital Universitario Marques	Santander		Spain	39008
62	Valme Hospital	Sevilla		Spain	41014
63	Hospital General Universitario de Valencia	Valencia		Spain	46014
64	Sahlgrenska University Hospital	Göteborg		Sweden	41685
65	Skånes Universitetssjukhus, Lund	Lund		Sweden	22185
66	Skanes Universitetssjukhus	Malmo		Sweden	20502
67	Karolinska Instituet	Stockholm		Sweden	14186
68	University of Birmingham	Edgbaston	Birmingham	United Kingdom	B15 2TH
69	Southampton University Hospital NHS Trust	Southhampton	Hampshire	United Kingdom	SO41 3QP
70	King's College Hospital	Denmark Hill	London	United Kingdom	SE5 9RS
71	The Liver Unit	Paddington	London	United Kingdom	W2 1NY
72	North Manchester General Hospital	Crumpsall	Manchester	United Kingdom	M8 5RB
73	Bristol Royal Infirmary	Bristol		United Kingdom	BS2 8HW
74	Queen Marys University of London	London		United Kingdom	E1 2AT
75	Royal Free Hospital and University College London Hospital	London		United Kingdom	NW3 2PF
76	Chelsea & Westminster Hospital	London		United Kingdom	SW109NH
77	Nottingham University Hospitals-NHS	Nottingham		United Kingdom	NG7 2UH

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Rob Hyland, DPhil, Gilead Sciences Study Director

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01682720
• Other Study ID Numbers: GS-US-334-0133; 2012-001942-16
• First Posted: Sep 11, 2012
• Last Update Posted: Oct 9, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Gilead Sciences: HCV; Genotype 2; Genotype 3
• Additional relevant MeSH terms: Hepatitis C; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 77 study sites in Europe. The first participant was screened on 19 September 2012. The last participant observation occurred on 08 January 2014.
Pre-assignment Detail	475 participants were screened and 421 were randomized. 419 participants were randomized and received at least 1 dose of study drug (Safety Analysis Set). 334 participants with genotype 2 or 3 hepatitis C virus (HCV) infection were randomized and received at least 1 dose of sofosbuvir (Full Analysis Set).

Arm/Group Title	Placebo 12 Weeks (GT2/3)	SOF 12 Weeks (GT2)	SOF 12 Weeks (GT3)	SOF 24 Weeks (GT3)
Arm/Group Description	Placebo to match sofosbuvir (SOF) + placebo to match ribavirin (RBV) for 12 weeks in participants with genotype (GT)2 or 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Period Title: Overall Study
STARTED	85	74	12	250
Included in Full Analysis Set	0	73	11	250
COMPLETED	0	69	5	211
NOT COMPLETED	85	5	7	39

Baseline Characteristics

Arm/Group Title	Placebo 12 Weeks (GT2/3)	SOF 12 Weeks (GT2)	SOF 12 Weeks (GT3)	SOF 24 Weeks (GT3)	Total
Arm/Group Description	Placebo to match SOF + placebo to match RBV for 12 weeks in participants with genotype 2 or 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.	Total of all reporting groups
Overall Participants	85	73	11	250	419
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (10.5)	58 (10.1)	46 (8.8)	48 (10.1)	50 (10.8)
Sex: Female, Male (Count of Participants)
Female	36 42.4%	33 45.2%	5 45.5%	95 38%	169 40.3%
Male	49 57.6%	40 54.8%	6 54.5%	155 62%	250 59.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	10 11.8%	6 8.2%	1 9.1%	36 14.4%	53 12.6%
Not Hispanic or Latino	71 83.5%	65 89%	10 90.9%	203 81.2%	349 83.3%
Not Permitted	4 4.7%	2 2.7%	0 0%	11 4.4%	17 4.1%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	1 1.2%	5 6.8%	0 0%	0 0%	6 1.4%
White	81 95.3%	65 89%	11 100%	236 94.4%	393 93.8%
Asian	3 3.5%	1 1.4%	0 0%	9 3.6%	13 3.1%
Not permitted	0 0%	2 2.7%	0 0%	5 2%	7 1.7%
Region of Enrollment (participants) [Number]
France	13 15.3%	15 20.5%	0 0%	53 21.2%	81 19.3%
Estonia	3 3.5%	2 2.7%	4 36.4%	6 2.4%	15 3.6%
Spain	11 12.9%	5 6.8%	1 9.1%	31 12.4%	48 11.5%
Poland	4 4.7%	0 0%	0 0%	18 7.2%	22 5.3%
Austria	4 4.7%	2 2.7%	0 0%	12 4.8%	18 4.3%
Netherlands	5 5.9%	6 8.2%	0 0%	14 5.6%	25 6%
Germany	14 16.5%	8 11%	1 9.1%	46 18.4%	69 16.5%
United Kingdom	17 20%	3 4.1%	4 36.4%	31 12.4%	55 13.1%
Italy	9 10.6%	25 34.2%	1 9.1%	27 10.8%	62 14.8%
Sweden	5 5.9%	7 9.6%	0 0%	12 4.8%	24 5.7%
HCV Genotype (participants) [Number]
Genotype 2	18 21.2%	73 100%	0 0%	0 0%	91 21.7%
Genotype 3	67 78.8%	0 0%	11 100%	250 100%	328 78.3%
Liver Cirrhosis (participants) [Number]
No	68 80%	62 84.9%	9 81.8%	190 76%	329 78.5%
Yes	17 20%	11 15.1%	2 18.2%	60 24%	90 21.5%
IL28b Status (participants) [Number]
CC	22 25.9%	24 32.9%	4 36.4%	86 34.4%	136 32.5%
CT	49 57.6%	41 56.2%	4 36.4%	131 52.4%	225 53.7%
TT	14 16.5%	8 11%	3 27.3%	33 13.2%	58 13.8%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.5 (0.69)	6.5 (0.70)	6.2 (0.77)	6.3 (0.74)	6.4 (0.72)
HCV RNA Category (participants) [Number]
< 6 log10 IU/mL	21 24.7%	16 21.9%	4 36.4%	72 28.8%	113 27%
≥ 6 log10 IU/mL	64 75.3%	57 78.1%	7 63.6%	178 71.2%	306 73%
Prior HCV Treatment Experience (participants) [Number]
Experienced	50 58.8%	41 56.2%	9 81.8%	145 58%	245 58.5%
Naive	35 41.2%	32 43.8%	2 18.2%	105 42%	174 41.5%
Response to prior HCV treatment (participants) [Number]
Interferon intolerant	0 0%	3 4.1%	0 0%	10 4%	13 3.1%
Nonresponse	18 21.2%	10 13.7%	4 36.4%	41 16.4%	73 17.4%
Relapse/Breakthrough	32 37.6%	28 38.4%	5 45.5%	94 37.6%	159 37.9%
Interferon Eligibility (participants) [Number]
Interferon eligible	30 35.3%	27 37%	2 18.2%	94 37.6%	153 36.5%
Interferon ineligible	5 5.9%	5 6.8%	0 0%	11 4.4%	21 5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks following the last dose of study drug. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants with genotype 2 or 3 HCV infection were randomized and received at least 1 dose of SOF.

Arm/Group Title	SOF 12 Weeks (GT2)	SOF 12 Weeks (GT3)	SOF 24 Weeks (GT3)
Arm/Group Description	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Measure Participants	73	11	250
Number [percentage of participants]	93.2 109.6%	27.3 37.4%	85.2 774.5%

2. Primary Outcome

Title	Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
Description	The percentage of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was analyzed.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants were randomized and received at least 1 dose of study drug.

Arm/Group Title	Placebo 12 Weeks (GT2/3)	SOF 12 Weeks (GT2/3)	SOF 24 Weeks (GT3)
Arm/Group Description	Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Measure Participants	85	84	250
Number [percentage of participants]	1.2 1.4%	1.2 1.6%	0.4 3.6%

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 SVR24 was defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.
Time Frame	Posttreatment Weeks 4 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants with genotype 2 or 3 HCV infection were randomized and received at least 1 dose of SOF.

Arm/Group Title	SOF 12 Weeks (GT2)	SOF 12 Weeks (GT3)	SOF 24 Weeks (GT3)
Arm/Group Description	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Measure Participants	73	11	250
SVR4	93.2 109.6%	45.5 62.3%	87.2 792.7%
SVR24	93.2 109.6%	27.3 37.4%	84.4 767.3%

4. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse
Description	Viral breakthrough was defined as having confirmed detectable HCV RNA levels (HCV RNA > LLOQ) after having previously had undetectable HCV RNA levels (HCV RNA < LLOQ) while on treatment. Viral relapse was defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) at end of treatment, but did not achieve an SVR. Data for this outcome measure was not collected for the Placebo 12 Weeks (GT2/3) group.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants with genotype 2 or 3 HCV infection were randomized and received at least 1 dose of SOF.

Arm/Group Title	SOF 12 Weeks (GT2)	SOF 12 Weeks (GT3)	SOF 24 Weeks (GT3)
Arm/Group Description	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.	SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Measure Participants	73	11	250
Viral breakthrough	0 0%	0 0%	0.4 3.6%
Viral relapse	6.8 8%	54.5 74.7%	14.0 127.3%

Adverse Events

Time Frame	Baseline up to Week 24 plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants were randomized and received at least 1 dose of study drug.
Arm/Group Title	Placebo 12 Weeks (GT2/3)		SOF 12 Weeks (GT2/3)		SOF 24 Weeks (GT3)
Arm/Group Description	Placebo to match SOF + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.		SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 or 3 HCV infection.		SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
All Cause Mortality
	Placebo 12 Weeks (GT2/3)		SOF 12 Weeks (GT2/3)		SOF 24 Weeks (GT3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo 12 Weeks (GT2/3)		SOF 12 Weeks (GT2/3)		SOF 24 Weeks (GT3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/85 (2.4%)		0/84 (0%)		10/250 (4%)
Cardiac disorders
Arrhythmia	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Gastrointestinal disorders
Adenocarcinoma of colon	1/85 (1.2%)		0/84 (0%)		0/250 (0%)
Haemorrhoidal haemorrhage	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Hepatobiliary disorders
Biliary colic	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Infections and infestations
Gastroenteritis	1/85 (1.2%)		0/84 (0%)		0/250 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Investigations
Amylase increased	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Lipase increased	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Metabolism and nutrition disorders
Hyperglycaemia	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Invasive ductal breast carcinoma	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Nervous system disorders
Complex regional pain syndrome	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Psychiatric disorders
Suicide attempt	0/85 (0%)		0/84 (0%)		1/250 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo 12 Weeks (GT2/3)		SOF 12 Weeks (GT2/3)		SOF 24 Weeks (GT3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/85 (70.6%)		72/84 (85.7%)		229/250 (91.6%)
Blood and lymphatic system disorders
Anaemia	1/85 (1.2%)		6/84 (7.1%)		17/250 (6.8%)
Gastrointestinal disorders
Nausea	9/85 (10.6%)		26/84 (31%)		33/250 (13.2%)
Diarrhoea	4/85 (4.7%)		4/84 (4.8%)		30/250 (12%)
Abdominal pain upper	6/85 (7.1%)		7/84 (8.3%)		15/250 (6%)
Abdominal pain	4/85 (4.7%)		1/84 (1.2%)		21/250 (8.4%)
Dyspepsia	0/85 (0%)		3/84 (3.6%)		15/250 (6%)
Constipation	1/85 (1.2%)		2/84 (2.4%)		13/250 (5.2%)
General disorders
Fatigue	16/85 (18.8%)		19/84 (22.6%)		75/250 (30%)
Asthenia	4/85 (4.7%)		21/84 (25%)		53/250 (21.2%)
Irritability	3/85 (3.5%)		4/84 (4.8%)		26/250 (10.4%)
Influenza like illness	5/85 (5.9%)		1/84 (1.2%)		16/250 (6.4%)
Pyrexia	2/85 (2.4%)		7/84 (8.3%)		9/250 (3.6%)
Chest pain	0/85 (0%)		5/84 (6%)		5/250 (2%)
Infections and infestations
Nasopharyngitis	9/85 (10.6%)		4/84 (4.8%)		36/250 (14.4%)
Influenza	0/85 (0%)		6/84 (7.1%)		12/250 (4.8%)
Metabolism and nutrition disorders
Decreased appetite	4/85 (4.7%)		5/84 (6%)		16/250 (6.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/85 (7.1%)		3/84 (3.6%)		25/250 (10%)
Myalgia	1/85 (1.2%)		4/84 (4.8%)		22/250 (8.8%)
Back pain	5/85 (5.9%)		5/84 (6%)		15/250 (6%)
Pain in extremity	1/85 (1.2%)		0/84 (0%)		13/250 (5.2%)
Nervous system disorders
Headache	23/85 (27.1%)		24/84 (28.6%)		74/250 (29.6%)
Dizziness	2/85 (2.4%)		5/84 (6%)		19/250 (7.6%)
Disturbance in attention	2/85 (2.4%)		1/84 (1.2%)		15/250 (6%)
Psychiatric disorders
Insomnia	2/85 (2.4%)		9/84 (10.7%)		41/250 (16.4%)
Sleep disorder	4/85 (4.7%)		4/84 (4.8%)		23/250 (9.2%)
Anxiety	2/85 (2.4%)		1/84 (1.2%)		13/250 (5.2%)
Depressed mood	2/85 (2.4%)		1/84 (1.2%)		13/250 (5.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/85 (1.2%)		12/84 (14.3%)		27/250 (10.8%)
Cough	4/85 (4.7%)		8/84 (9.5%)		27/250 (10.8%)
Dyspnoea exertional	0/85 (0%)		6/84 (7.1%)		9/250 (3.6%)
Skin and subcutaneous tissue disorders
Pruritus	8/85 (9.4%)		20/84 (23.8%)		67/250 (26.8%)
Dry skin	5/85 (5.9%)		8/84 (9.5%)		31/250 (12.4%)
Rash	2/85 (2.4%)		1/84 (1.2%)		24/250 (9.6%)
Eczema	0/85 (0%)		3/84 (3.6%)		14/250 (5.6%)

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