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Phase 3 Study of Sofosbuvir and Ribavirin (FISSION)

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ClinicalTrials.gov Identifier: NCT01497366
Recruitment Status : Completed
First Posted : December 22, 2011
Results First Posted : April 2, 2014
Last Update Posted : April 2, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: Sofosbuvir
Drug: PEG
Drug: RBV
Enrollment 527
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 Details 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
Hide 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
Reason Not Completed
Virologic failure             2             50
Lost to Follow-up             11             10
Withdrawal by Subject             6             6
Initiated Non-protocol HCV Treatment             7             0
Other             5             0
Death             1             1
Randomized but not treated             7             21
Arm/Group Title Sofosbuvir+RBV PEG+RBV Total
Hide 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 Number of Baseline Participants 256 243 499
Hide Baseline Analysis Population Description
Safety Analysis Set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 256 participants 243 participants 499 participants
48  (10.8) 48  (11.4) 48  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 256 participants 243 participants 499 participants
Female
85
  33.2%
87
  35.8%
172
  34.5%
Male
171
  66.8%
156
  64.2%
327
  65.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 256 participants 243 participants 499 participants
Hispanic or Latino
41
  16.0%
31
  12.8%
72
  14.4%
Not Hispanic or Latino
215
  84.0%
212
  87.2%
427
  85.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
Black or African American 12 5 17
White 223 212 435
Asian 14 15 29
American Indian/Alaska Native/First Nations 4 4 8
Hawaiian or Pacific Islander 2 6 8
Black and White 1 0 1
South American 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
United States 165 151 316
Canada 15 24 39
Australia 32 29 61
Netherlands 3 1 4
Italy 8 4 12
New Zealand 29 30 59
Sweden 4 4 8
Hepatitis C Virus (HCV) genotype  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
Genotype 1 3 0 3
Genotype 2 70 67 137
Genotype 3 183 176 359
Baseline HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 256 participants 243 participants 499 participants
6.0  (0.82) 6.0  (0.78) 6.0  (0.80)
Baseline HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
< 6 log10 IU/mL 108 106 214
≥ 6 log10 IU/mL 148 137 285
IL28b genotype  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
CC 108 106 214
CT 121 98 219
TT 25 38 63
Missing 2 1 3
Cirrhosis  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 256 participants 243 participants 499 participants
No 205 189 394
Yes 50 50 100
Missing 1 4 5
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Stopping All Study Drugs (SVR12)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 253 243
Measure Type: Number
Unit of Measure: percentage of participants
67 67
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sofosbuvir+RBV, PEG+RBV
Comments [Not Specified]
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%.
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-7.5 to 8.0
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
Hide Description [Not Specified]
Time Frame Up to 24 weeks plus 30 days following the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 256 243
Measure Type: Number
Unit of Measure: participants
AEs leading to discontinuation of any study drug 3 29
Serious AEs 7 3
Grade 3 laboratory abnormalities 33 80
Grade 4 laboratory abnormalities 3 21
Deaths 1 0
3.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24)
Hide Description SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation.
Time Frame Post-treatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 253 243
Measure Type: Number
Unit of Measure: percentage of participants
66.8 65.4
4.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ on Treatment
Hide Description [Not Specified]
Time Frame Up to 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir (SOF)+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 253 243
Measure Type: Number
Unit of Measure: percentage of participants
Week 1 (SOF+RBV, n = 252; PEG+RBV, n = 243) 43.7 6.6
Week 2 (SOF+RBV, n = 251; PEG+RBV, n = 241) 92.0 31.5
Week 4 (SOF+RBV, n = 250; PEG+RBV, n = 236) 99.6 66.9
Week 8 (SOF+RBV, n = 248; PEG+RBV, n = 231) 99.6 85.7
Week 12 (SOF+RBV, n = 244; PEG+RBV, n = 224) 99.2 92.4
5.Secondary Outcome
Title Change From Baseline in HCV RNA
Hide Description [Not Specified]
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir (SOF)+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 253 243
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 253 243
Measure Type: Number
Unit of Measure: percentage of participants
0.4 7.4
7.Secondary Outcome
Title Percentage of Participants With Viral Relapse Following Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide Arm/Group Description:
Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
Participants were randomized to receive PEG+RBV for 24 weeks.
Overall Number of Participants Analyzed 249 217
Measure Type: Number
Unit of Measure: percentage of participants
30.5 22.6
Time Frame Up to 24 weeks plus 30 days following the last dose of study drug
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sofosbuvir+RBV PEG+RBV
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Sofosbuvir+RBV PEG+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   7/256 (2.73%)   3/243 (1.23%) 
Blood and lymphatic system disorders     
Anaemia † 1  1/256 (0.39%)  0/243 (0.00%) 
Cardiac disorders     
Atrioventriclar shock † 1  0/256 (0.00%)  1/243 (0.41%) 
General disorders     
Chest pain † 1  1/256 (0.39%)  0/243 (0.00%) 
Immune system disorders     
Allergy to arthropod sting † 1  1/256 (0.39%)  0/243 (0.00%) 
Infections and infestations     
Cellulitis † 1  1/256 (0.39%)  0/243 (0.00%) 
Infection † 1  0/256 (0.00%)  1/243 (0.41%) 
Osteomyelitis chronic † 1  1/256 (0.39%)  0/243 (0.00%) 
Urinary tract infection † 1  1/256 (0.39%)  0/243 (0.00%) 
Injury, poisoning and procedural complications     
Clavicle fracture † 1  0/256 (0.00%)  1/243 (0.41%) 
Rib fracture † 1  0/256 (0.00%)  1/243 (0.41%) 
Toxicity to various agents † 1  1/256 (0.39%)  0/243 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer in situ † 1  0/256 (0.00%)  1/243 (0.41%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease † 1  1/256 (0.39%)  0/243 (0.00%) 
Pneumothorax † 1  0/256 (0.00%)  1/243 (0.41%) 
†
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%
Sofosbuvir+RBV PEG+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   219/256 (85.55%)   233/243 (95.88%) 
Blood and lymphatic system disorders     
Anaemia † 1  20/256 (7.81%)  28/243 (11.52%) 
Neutropenia † 1  0/256 (0.00%)  30/243 (12.35%) 
Thrombocytopenia † 1  0/256 (0.00%)  23/243 (9.47%) 
Gastrointestinal disorders     
Nausea † 1  46/256 (17.97%)  70/243 (28.81%) 
Diarrhoea † 1  23/256 (8.98%)  42/243 (17.28%) 
Vomiting † 1  17/256 (6.64%)  23/243 (9.47%) 
Dry mouth † 1  10/256 (3.91%)  15/243 (6.17%) 
General disorders     
Fatigue † 1  92/256 (35.94%)  134/243 (55.14%) 
Irritability † 1  25/256 (9.77%)  40/243 (16.46%) 
Chills † 1  7/256 (2.73%)  44/243 (18.11%) 
Influenza like illness † 1  7/256 (2.73%)  44/243 (18.11%) 
Pyrexia † 1  6/256 (2.34%)  33/243 (13.58%) 
Pain † 1  5/256 (1.95%)  30/243 (12.35%) 
Injection site reaction † 1  0/256 (0.00%)  17/243 (7.00%) 
Injection site erythema † 1  0/256 (0.00%)  14/243 (5.76%) 
Infections and infestations     
Nasopharyngitis † 1  13/256 (5.08%)  5/243 (2.06%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  17/256 (6.64%)  44/243 (18.11%) 
Musculoskeletal and connective tissue disorders     
Myalgia † 1  21/256 (8.20%)  40/243 (16.46%) 
Arthralgia † 1  15/256 (5.86%)  35/243 (14.40%) 
Back pain † 1  9/256 (3.52%)  20/243 (8.23%) 
Nervous system disorders     
Headache † 1  64/256 (25.00%)  108/243 (44.44%) 
Dizziness † 1  27/256 (10.55%)  33/243 (13.58%) 
Psychiatric disorders     
Insomnia † 1  31/256 (12.11%)  71/243 (29.22%) 
Depression † 1  14/256 (5.47%)  35/243 (14.40%) 
Anxiety † 1  11/256 (4.30%)  16/243 (6.58%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  19/256 (7.42%)  21/243 (8.64%) 
Dyspnoea † 1  18/256 (7.03%)  20/243 (8.23%) 
Oropharyngeal pain † 1  14/256 (5.47%)  10/243 (4.12%) 
Skin and subcutaneous tissue disorders     
Rash † 1  23/256 (8.98%)  43/243 (17.70%) 
Pruritus † 1  19/256 (7.42%)  42/243 (17.28%) 
Alopecia † 1  12/256 (4.69%)  24/243 (9.88%) 
Dry skin † 1  11/256 (4.30%)  23/243 (9.47%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
[Not Specified]
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01497366    
Other Study ID Numbers: P7977-1231
First Submitted: December 19, 2011
First Posted: December 22, 2011
Results First Submitted: January 15, 2014
Results First Posted: April 2, 2014
Last Update Posted: April 2, 2014