Trial Outcomes & Findings for Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION) (NCT NCT01604850)

Last Updated: 2014-05-28

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

202 participants

Primary outcome timeframe

Posttreatment Week 12

Results posted on

2014-05-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	SOF+RBV+Placebo 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.	SOF+RBV 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 Study STARTED	103	99
Overall Study Enrolled and Treated	103	98
Overall Study COMPLETED	51	69
Overall Study NOT COMPLETED	52	30

Reasons for withdrawal

Reasons for withdrawal
Measure	SOF+RBV+Placebo 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.	SOF+RBV 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 Study Enrolled but never treated	0	1
Overall Study Efficacy Failure	50	29
Overall Study Lost to Follow-up	1	0
Overall Study Subject withdrew consent	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SOF+RBV+Placebo n=103 Participants 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.	SOF+RBV n=98 Participants 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 n=201 Participants Total of all reporting groups
Age, Continuous	54 years STANDARD_DEVIATION 7.7 • n=5 Participants	54 years STANDARD_DEVIATION 7.8 • n=7 Participants	54 years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	67 Participants n=7 Participants	140 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized White	88 participants n=5 Participants	86 participants n=7 Participants	174 participants n=5 Participants
Race/Ethnicity, Customized Asian	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized American Indian/ Alaska Native/ First Nations	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Hawaiian or Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United States	74 participants n=5 Participants	76 participants n=7 Participants	150 participants n=5 Participants
Region of Enrollment Canada	26 participants n=5 Participants	17 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment New Zealand	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants
Hepatitis C Virus (HCV) genotype Genotype 1	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Hepatitis C Virus (HCV) genotype Genotype 2	36 participants n=5 Participants	32 participants n=7 Participants	68 participants n=5 Participants
Hepatitis C Virus (HCV) genotype Genotype 3	64 participants n=5 Participants	63 participants n=7 Participants	127 participants n=5 Participants
HCV RNA	6.5 log10 IU/mL STANDARD_DEVIATION 0.67 • n=5 Participants	6.5 log10 IU/mL STANDARD_DEVIATION 0.63 • n=7 Participants	6.5 log10 IU/mL STANDARD_DEVIATION 0.65 • n=5 Participants
HCV RNA Category < 6 log10 IU/mL	26 participants n=5 Participants	29 participants n=7 Participants	55 participants n=5 Participants
HCV RNA Category ≥ 6 log10 IU/mL	77 participants n=5 Participants	69 participants n=7 Participants	146 participants n=5 Participants
IL28 Genotype CC	31 participants n=5 Participants	30 participants n=7 Participants	61 participants n=5 Participants
IL28 Genotype CT	53 participants n=5 Participants	56 participants n=7 Participants	109 participants n=5 Participants
IL28 Genotype TT	19 participants n=5 Participants	12 participants n=7 Participants	31 participants n=5 Participants
Cirrhosis (Y/N) No	66 participants n=5 Participants	66 participants n=7 Participants	132 participants n=5 Participants
Cirrhosis (Y/N) Yes	36 participants n=5 Participants	32 participants n=7 Participants	68 participants n=5 Participants
Cirrhosis (Y/N) Missing	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Response to Prior HCV Treatment Nonresponse	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants
Response to Prior HCV Treatment Relapse/Breakthrough	78 participants n=5 Participants	73 participants n=7 Participants	151 participants n=5 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=100 Participants 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.	SOF+RBV n=95 Participants 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.
Percentage of Participants Achieving SVR12	51.0 percentage of participants	72.6 percentage of participants

PRIMARY outcome

Timeframe: Baseline to Week 16

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

Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment.

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=103 Participants 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.	SOF+RBV n=98 Participants 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.
Adverse Events Leading to Permanent Discontinuation of Study Drug	1 participants	0 participants

SECONDARY outcome

Timeframe: Posttreatment Week 4

Population: 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.

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).

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=100 Participants 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.	SOF+RBV n=95 Participants 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.
Percentage of Participants Achieving SVR4	56.0 percentage of participants	76.8 percentage of participants

SECONDARY outcome

Timeframe: Posttreatment Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=100 Participants 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.	SOF+RBV n=95 Participants 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.
Percentage of Participants Achieving SVR24	50.0 percentage of participants	71.6 percentage of participants

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: 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.

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).

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=100 Participants 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.	SOF+RBV n=95 Participants 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.
Percentage of Participants With Viral Breakthrough	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: End of treatment to posttreatment Week 24

Population: 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.

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).

Outcome measures

Outcome measures
Measure	SOF+RBV+Placebo n=100 Participants 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.	SOF+RBV n=95 Participants 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.
Percentage of Participants With Viral Relapse	47 participants	26 participants

Adverse Events

SOF+RBV+Placebo

Serious events: 5 serious events

Other events: 92 other events

Deaths: 0 deaths

SOF+RBV

Serious events: 3 serious events

Other events: 86 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SOF+RBV+Placebo n=103 participants at risk 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.	SOF+RBV n=98 participants at risk 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.
Gastrointestinal disorders Abdominal pain	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Oesophageal varices haemorrhage	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
General disorders Non-cardiac chest pain	0.00% 0/103 • Baseline to posttreatment Week 24 plus 30 days	1.0% 1/98 • Baseline to posttreatment Week 24 plus 30 days
Hepatobiliary disorders Portal vein thrombosis	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
Injury, poisoning and procedural complications Overdose	0.00% 0/103 • Baseline to posttreatment Week 24 plus 30 days	1.0% 1/98 • Baseline to posttreatment Week 24 plus 30 days
Injury, poisoning and procedural complications Upper limb fracture	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	2.9% 3/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days
Psychiatric disorders Suicide attempt	0.00% 0/103 • Baseline to posttreatment Week 24 plus 30 days	1.0% 1/98 • Baseline to posttreatment Week 24 plus 30 days
General disorders Pyrexia	0.97% 1/103 • Baseline to posttreatment Week 24 plus 30 days	0.00% 0/98 • Baseline to posttreatment Week 24 plus 30 days

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER

Measure	SOF+RBV+Placebo n=103 participants at risk 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.	SOF+RBV n=98 participants at risk 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.
Blood and lymphatic system disorders Anaemia	10.7% 11/103 • Baseline to posttreatment Week 24 plus 30 days	4.1% 4/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Nausea	21.4% 22/103 • Baseline to posttreatment Week 24 plus 30 days	20.4% 20/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Diarrhoea	14.6% 15/103 • Baseline to posttreatment Week 24 plus 30 days	6.1% 6/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Abdominal pain	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Dyspepsia	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	3.1% 3/98 • Baseline to posttreatment Week 24 plus 30 days
Gastrointestinal disorders Constipation	1.9% 2/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
General disorders Fatigue	44.7% 46/103 • Baseline to posttreatment Week 24 plus 30 days	46.9% 46/98 • Baseline to posttreatment Week 24 plus 30 days
General disorders Irritability	14.6% 15/103 • Baseline to posttreatment Week 24 plus 30 days	11.2% 11/98 • Baseline to posttreatment Week 24 plus 30 days
General disorders Pain	3.9% 4/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Infections and infestations Upper respiratory tract infection	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Injury, poisoning and procedural complications Contusion	3.9% 4/103 • Baseline to posttreatment Week 24 plus 30 days	8.2% 8/98 • Baseline to posttreatment Week 24 plus 30 days
Musculoskeletal and connective tissue disorders Arthralgia	10.7% 11/103 • Baseline to posttreatment Week 24 plus 30 days	9.2% 9/98 • Baseline to posttreatment Week 24 plus 30 days
Musculoskeletal and connective tissue disorders Myalgia	7.8% 8/103 • Baseline to posttreatment Week 24 plus 30 days	9.2% 9/98 • Baseline to posttreatment Week 24 plus 30 days
Musculoskeletal and connective tissue disorders Muscle spasms	7.8% 8/103 • Baseline to posttreatment Week 24 plus 30 days	8.2% 8/98 • Baseline to posttreatment Week 24 plus 30 days
Musculoskeletal and connective tissue disorders Back pain	4.9% 5/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Nervous system disorders Headache	25.2% 26/103 • Baseline to posttreatment Week 24 plus 30 days	32.7% 32/98 • Baseline to posttreatment Week 24 plus 30 days
Nervous system disorders Dizziness	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Nervous system disorders Dysgeusia	2.9% 3/103 • Baseline to posttreatment Week 24 plus 30 days	6.1% 6/98 • Baseline to posttreatment Week 24 plus 30 days
Nervous system disorders Disturbance in attention	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	1.0% 1/98 • Baseline to posttreatment Week 24 plus 30 days
Psychiatric disorders Insomnia	20.4% 21/103 • Baseline to posttreatment Week 24 plus 30 days	28.6% 28/98 • Baseline to posttreatment Week 24 plus 30 days
Psychiatric disorders Anxiety	7.8% 8/103 • Baseline to posttreatment Week 24 plus 30 days	9.2% 9/98 • Baseline to posttreatment Week 24 plus 30 days
Psychiatric disorders Depression	5.8% 6/103 • Baseline to posttreatment Week 24 plus 30 days	6.1% 6/98 • Baseline to posttreatment Week 24 plus 30 days
Respiratory, thoracic and mediastinal disorders Cough	9.7% 10/103 • Baseline to posttreatment Week 24 plus 30 days	13.3% 13/98 • Baseline to posttreatment Week 24 plus 30 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.8% 8/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Skin and subcutaneous tissue disorders Pruritus	11.7% 12/103 • Baseline to posttreatment Week 24 plus 30 days	7.1% 7/98 • Baseline to posttreatment Week 24 plus 30 days
Skin and subcutaneous tissue disorders Rash	6.8% 7/103 • Baseline to posttreatment Week 24 plus 30 days	12.2% 12/98 • Baseline to posttreatment Week 24 plus 30 days
Skin and subcutaneous tissue disorders Dry skin	6.8% 7/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days
Metabolism and nutrition disorders Decreased Appetite	8.7% 9/103 • Baseline to posttreatment Week 24 plus 30 days	5.1% 5/98 • Baseline to posttreatment Week 24 plus 30 days