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Sofosbuvir With Peginterferon Alfa 2a and Ribavirin for 12 Weeks in Treatment-Naive Subjects With Chronic Genotype 1, 4, 5, or 6 HCV Infection (NEUTRINO)

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ClinicalTrials.gov Identifier: NCT01641640
Recruitment Status : Completed
First Posted : July 17, 2012
Results First Posted : May 8, 2014
Last Update Posted : May 8, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Hepatitis C
Interventions Drug: Sofosbuvir
Drug: RBV
Drug: PEG
Enrollment 328
Recruitment Details Subjects were enrolled in a total of 55 study sites in the United States. The first participant was screened on 18 June 2012. The last participant observation was on 16 April 2013.
Pre-assignment Details 456 participants were screened and 328 were enrolled; 327 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Arm/Group Title Sofosbuvir+PEG+RBV
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Participants received Sofosbuvir+pegylated interferon alfa 2a (PEG)+ribavirin (RBV) for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Period Title: Overall Study
Started 328
Enrolled and Treated 327
Completed 292
Not Completed 36
Reason Not Completed
Enrolled but not treated             1
Efficacy failure             29
Lost to Follow-up             3
Withdrawal by Subject             2
Adverse Event             1
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Baseline Participants 327
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Safety Analysis Set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 327 participants
52  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants
Female
118
  36.1%
Male
209
  63.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants
Hispanic or Latino
46
  14.1%
Not Hispanic or Latino
281
  85.9%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants
Black or African American 54
White 257
Asian 7
American Indian/ Alaska Native/ First Nations 6
Hawaiian or Pacific Islander 2
Other 1
Hepatitis C Virus (HCV) genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants
Genotype 1a/1b 1
Genotype 1a 225
Genotype 1b 66
Genotype 4 28
Genotype 5 1
Genotype 6 6
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 327 participants
6.4  (0.67)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants
< 6 log10 IU/mL 71
≥ 6 log10 IU/mL 256
IL28 Genotype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 327 participants
CC 95
CT 181
TT 51
[1]
Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response (SVR)12
Hide Description SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after cessation of therapy.
Time Frame Posttreatment Week 12
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Full Analysis Set
Arm/Group Title Sofosbuvir+PEG+RBV
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Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 327
Measure Type: Number
Unit of Measure: percentage of participants
91
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sofosbuvir+PEG+RBV
Comments Superiority would be demonstrated if the SVR12 rate was higher than the 60% null SVR rate based on historical control data.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Binomial exact test
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug
Hide Description The number of participants experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. Participants discontinuing study drug were permitted to remain on the study for further assessments.
Time Frame Baseline to Week 12
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description:

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 327
Measure Type: Number
Unit of Measure: participants
Anaemia 2
Haemolytic anaemia 1
Neutropenia 1
Vision blurred 1
Blood creatinine increased 1
Haemoglobin abnormal 1
Dermatitis 1
3.Secondary Outcome
Title Percentage of Participants Achieving SVR4
Hide Description SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy
Time Frame Posttreatment Week 4
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Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description:

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 327
Measure Type: Number
Unit of Measure: percentage of participants
92.4
4.Secondary Outcome
Title Percentage of Participants Achieving SVR24
Hide Description SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy
Time Frame Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description:

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 327
Measure Type: Number
Unit of Measure: percentage of participants
90.5
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.
Time Frame Baseline to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description:

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 327
Measure Type: Number
Unit of Measure: percentage of participants
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.
Time Frame End of treatment 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+PEG+RBV
Hide Arm/Group Description:

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

Overall Number of Participants Analyzed 326
Measure Type: Number
Unit of Measure: percentage of participants
8.6
Time Frame Baseline to Week 12 plus 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sofosbuvir+PEG+RBV
Hide Arm/Group Description

Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.

Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets.

All-Cause Mortality
Sofosbuvir+PEG+RBV
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sofosbuvir+PEG+RBV
Affected / at Risk (%)
Total   4/327 (1.22%) 
Blood and lymphatic system disorders   
Anaemia  1  1/327 (0.31%) 
Leukopenia  1  1/327 (0.31%) 
Gastrointestinal disorders   
Abdominal pain  1  1/327 (0.31%) 
General disorders   
Non-cardiac chest pain  1  1/327 (0.31%) 
Pyrexia  1  1/327 (0.31%) 
Immune system disorders   
Cryoglobulonaemia  1  1/327 (0.31%) 
Injury, poisoning and procedural complications   
Spinal compression fracture  1  1/327 (0.31%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Laryngeal cancer  1  1/327 (0.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sofosbuvir+PEG+RBV
Affected / at Risk (%)
Total   310/327 (94.80%) 
Blood and lymphatic system disorders   
Anaemia  1  68/327 (20.80%) 
Neutropenia  1  54/327 (16.51%) 
Gastrointestinal disorders   
Nausea  1  112/327 (34.25%) 
Diarrhoea  1  39/327 (11.93%) 
Vomiting  1  39/327 (11.93%) 
Constipation  1  20/327 (6.12%) 
General disorders   
Fatigue  1  194/327 (59.33%) 
Pyrexia  1  57/327 (17.43%) 
Chills  1  54/327 (16.51%) 
Influenza like illness  1  51/327 (15.60%) 
Irritability  1  43/327 (13.15%) 
Pain  1  33/327 (10.09%) 
Injection site reaction  1  27/327 (8.26%) 
Injection site erythema  1  21/327 (6.42%) 
Metabolism and nutrition disorders   
Decreased appetite  1  58/327 (17.74%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  47/327 (14.37%) 
Myalgia  1  45/327 (13.76%) 
Back pain  1  19/327 (5.81%) 
Nervous system disorders   
Headache  1  118/327 (36.09%) 
Dizziness  1  41/327 (12.54%) 
Psychiatric disorders   
Insomnia  1  81/327 (24.77%) 
Depression  1  31/327 (9.48%) 
Anxiety  1  26/327 (7.95%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  40/327 (12.23%) 
Cough  1  34/327 (10.40%) 
Oropharyngeal pain  1  17/327 (5.20%) 
Skin and subcutaneous tissue disorders   
Rash  1  60/327 (18.35%) 
Pruritus  1  56/327 (17.13%) 
Alopecia  1  22/327 (6.73%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (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
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Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
EMail: ClinicalTrialDisclosures@gilead.com
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641640     History of Changes
Other Study ID Numbers: GS-US-334-0110
First Submitted: July 9, 2012
First Posted: July 17, 2012
Results First Submitted: February 25, 2014
Results First Posted: May 8, 2014
Last Update Posted: May 8, 2014