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Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION) (FUSION)

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ClinicalTrials.gov Identifier: NCT01604850
Recruitment Status : Completed
First Posted : May 24, 2012
Results First Posted : May 1, 2014
Last Update Posted : May 28, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Hepatitis C
Interventions Drug: SOF
Drug: RBV
Drug: Placebo to match SOF
Drug: Placebo to match RBV
Enrollment 202
Recruitment Details Subjects were enrolled in a total of 57 study sites in the United States, Canada, and New Zealand. The first participant was screened on 04 June 2012. The last participant observation was on 08 May 2013.
Pre-assignment Details 277 participants were screened and 202 were randomized. Of those participants randomized, 201 received at least one dose of study drug, and comprise the Safety Analysis Set; 195 of those participants with genotypes 2 or 3 HCV infection were treated and comprise the Full Analysis Set.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description

Participants were randomized to receive sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Period Title: Overall Study
Started 103 99
Enrolled and Treated 103 98
Completed 51 69
Not Completed 52 30
Reason Not Completed
Enrolled but never treated             0             1
Efficacy Failure             50             29
Lost to Follow-up             1             0
Subject withdrew consent             1             0
Arm/Group Title SOF+RBV+Placebo SOF+RBV Total
Hide Arm/Group Description

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Total of all reporting groups
Overall Number of Baseline Participants 103 98 201
Hide Baseline Analysis Population Description
Participants in the Safety Analysis Set (randomized and received at least 1 dose of study drug) were analyzed for baseline characteristics.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants 98 participants 201 participants
54  (7.7) 54  (7.8) 54  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
Female
30
  29.1%
31
  31.6%
61
  30.3%
Male
73
  70.9%
67
  68.4%
140
  69.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
Black or African American 5 1 6
White 88 86 174
Asian 7 5 12
American Indian/ Alaska Native/ First Nations 1 3 4
Hawaiian or Pacific Islander 0 1 1
Other 2 2 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
United States 74 76 150
Canada 26 17 43
New Zealand 3 5 8
Hepatitis C Virus (HCV) genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
Genotype 1 3 3 6
Genotype 2 36 32 68
Genotype 3 64 63 127
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 103 participants 98 participants 201 participants
6.5  (0.67) 6.5  (0.63) 6.5  (0.65)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
< 6 log10 IU/mL 26 29 55
≥ 6 log10 IU/mL 77 69 146
IL28 Genotype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
CC 31 30 61
CT 53 56 109
TT 19 12 31
[1]
Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.
Cirrhosis (Y/N)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
No 66 66 132
Yes 36 32 68
Missing 1 0 1
Response to Prior HCV Treatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 103 participants 98 participants 201 participants
Nonresponse 25 25 50
Relapse/Breakthrough 78 73 151
1.Primary Outcome
Title Percentage of Participants Achieving SVR12
Hide Description

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

For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

Time Frame Posttreatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 100 95
Measure Type: Number
Unit of Measure: percentage of participants
51.0 72.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF+RBV+Placebo, SOF+RBV
Comments A sample size of 100 subjects in each group would provide over 97% power to detect at least 20% improvement in SVR12 rate from the assumed null rate of 25% using 2-sided exact 1-sample binomial test at significance level of 0.025.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments P-value is from the Cochran-Mantel-Haenszel (CMH) test stratified by the randomization stratification factor (ie, presence/absence of cirrhosis, genotype 2 or 3).
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Proportion difference
Estimated Value -22.4
Confidence Interval (2-Sided) 95%
-34.4 to -10.3
Estimation Comments The difference in proportions between treatment groups and associated 95% confidence interval (CI) are calculated based on stratum-adjusted Mantel-Haenszel proportions.
2.Primary Outcome
Title Adverse Events Leading to Permanent Discontinuation of Study Drug
Hide Description Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 103 98
Measure Type: Number
Unit of Measure: participants
1 0
3.Secondary Outcome
Title Percentage of Participants Achieving SVR4
Hide Description

SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy.

For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

Time Frame Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 100 95
Measure Type: Number
Unit of Measure: percentage of participants
56.0 76.8
4.Secondary Outcome
Title Percentage of Participants Achieving SVR24
Hide Description

SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy.

For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

Time Frame Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 100 95
Measure Type: Number
Unit of Measure: percentage of participants
50.0 71.6
5.Secondary Outcome
Title Percentage of Participants With Viral Breakthrough
Hide Description

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

For the purposes of this efficacy analysis, assessments were made during active treatment (up to Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 100 95
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.0
6.Secondary Outcome
Title Percentage of Participants With Viral Relapse
Hide Description

Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.

For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

Time Frame End of treatment to posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included all participants with genotype 2 or 3 HCV infection who were randomized and received at least 1 dose of study drug.
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description:

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 100 95
Measure Type: Number
Unit of Measure: participants
47 26
Time Frame Baseline to posttreatment Week 24 plus 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SOF+RBV+Placebo SOF+RBV
Hide Arm/Group Description

Participants were randomized to receive sofosbuvir+RBV for 12 weeks, followed by placebo to match sofosbuvir plus placebo to match RBV for 4 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets. Placebo to match sofosbuvir and placebo to match RBV were also administered as oral tablets.

Participants were randomized to receive sofosbuvir+RBV for 16 weeks.

Sofosbuvir (400 mg) was administered as an oral tablet and RBV (1000-1200 mg) as 200 mg oral tablets.

All-Cause Mortality
SOF+RBV+Placebo SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
SOF+RBV+Placebo SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   5/103 (4.85%)   3/98 (3.06%) 
Gastrointestinal disorders     
Abdominal pain  1  1/103 (0.97%)  0/98 (0.00%) 
Oesophageal varices haemorrhage  1  1/103 (0.97%)  0/98 (0.00%) 
General disorders     
Non-cardiac chest pain  1  0/103 (0.00%)  1/98 (1.02%) 
Pyrexia  1  1/103 (0.97%)  0/98 (0.00%) 
Hepatobiliary disorders     
Portal vein thrombosis  1  1/103 (0.97%)  0/98 (0.00%) 
Injury, poisoning and procedural complications     
Overdose  1  0/103 (0.00%)  1/98 (1.02%) 
Upper limb fracture  1  1/103 (0.97%)  0/98 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic neoplasm malignant  1  3/103 (2.91%)  0/98 (0.00%) 
Basal cell carcinoma  1  1/103 (0.97%)  0/98 (0.00%) 
Psychiatric disorders     
Suicide attempt  1  0/103 (0.00%)  1/98 (1.02%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF+RBV+Placebo SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   92/103 (89.32%)   86/98 (87.76%) 
Blood and lymphatic system disorders     
Anaemia  1  11/103 (10.68%)  4/98 (4.08%) 
Gastrointestinal disorders     
Nausea  1  22/103 (21.36%)  20/98 (20.41%) 
Diarrhoea  1  15/103 (14.56%)  6/98 (6.12%) 
Abdominal pain  1  6/103 (5.83%)  5/98 (5.10%) 
Dyspepsia  1  6/103 (5.83%)  3/98 (3.06%) 
Constipation  1  2/103 (1.94%)  5/98 (5.10%) 
General disorders     
Fatigue  1  46/103 (44.66%)  46/98 (46.94%) 
Irritability  1  15/103 (14.56%)  11/98 (11.22%) 
Pain  1  4/103 (3.88%)  5/98 (5.10%) 
Infections and infestations     
Upper respiratory tract infection  1  6/103 (5.83%)  5/98 (5.10%) 
Injury, poisoning and procedural complications     
Contusion  1  4/103 (3.88%)  8/98 (8.16%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  9/103 (8.74%)  5/98 (5.10%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  11/103 (10.68%)  9/98 (9.18%) 
Myalgia  1  8/103 (7.77%)  9/98 (9.18%) 
Muscle spasms  1  8/103 (7.77%)  8/98 (8.16%) 
Back pain  1  5/103 (4.85%)  5/98 (5.10%) 
Nervous system disorders     
Headache  1  26/103 (25.24%)  32/98 (32.65%) 
Dizziness  1  6/103 (5.83%)  5/98 (5.10%) 
Dysgeusia  1  3/103 (2.91%)  6/98 (6.12%) 
Disturbance in attention  1  6/103 (5.83%)  1/98 (1.02%) 
Psychiatric disorders     
Insomnia  1  21/103 (20.39%)  28/98 (28.57%) 
Anxiety  1  8/103 (7.77%)  9/98 (9.18%) 
Depression  1  6/103 (5.83%)  6/98 (6.12%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  10/103 (9.71%)  13/98 (13.27%) 
Dyspnoea  1  8/103 (7.77%)  5/98 (5.10%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  12/103 (11.65%)  7/98 (7.14%) 
Rash  1  7/103 (6.80%)  12/98 (12.24%) 
Dry skin  1  7/103 (6.80%)  5/98 (5.10%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
EMail: ClinicalTrialDisclosures@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01604850    
Other Study ID Numbers: GS-US-334-0108
First Submitted: May 21, 2012
First Posted: May 24, 2012
Results First Submitted: March 31, 2014
Results First Posted: May 1, 2014
Last Update Posted: May 28, 2014