Phase 3 Study of Sofosbuvir and Ribavirin

Hepatitis C Clinical Trial

— FISSION  

Official title:

A Phase 3, Multicenter, Randomized, Active-Controlled Study to Investigate the Safety and Efficacy of PSI-7977 and Ribavirin for 12 Weeks Compared to Pegylated Interferon and Ribavirin for 24 Weeks in Treatment-Naïve Patients With Chronic Genotype 2 or 3 HCV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01497366
• Other study ID #: P7977-1231
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2011
• Last updated: March 4, 2014
• Start date: December 2011
• Est. completion date: April 2013

Study information

• Verified date: March 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study was to assess the safety and efficacy of sofosbuvir (GS-7977; PSI-7977) in combination with ribavirin (RBV) administered for 12 weeks compared with pegylated interferon (PEG)/RBV administered for 24 weeks in treatment-naive patients with Hepatitis C (HCV) genotype 2 or 3. Efficacy was assessed by the rate of sustained viral response (SVR) 12 weeks after the discontinuation of therapy (SVR12). This was a non-inferiority study, and if non-inferiority was demonstrated, the study was then allowed to test for superiority.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 527
• Est. completion date: April 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic Genotype 2 or 3 HCV-infection

• Naive to all HCV antiviral treatment(s)

Exclusion Criteria:

• Positive test at Screening for HBsAg, anti-hepatitis B core immunoglobulin M antibody (anti-HBc IgM Ab), or anti-HIV Ab

• History of any other clinically significant chronic liver disease

• A history consistent with decompensated liver disease

• History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or a history of malignancy, that makes the subject unsuitable for the study.

• Participation in a clinical study within 3 months prior to first dose

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Sofosbuvir
Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily
• PEG
Pegylated interferon alfa-2a (PEG) 180 µg administered once weekly by subcutaneous injection
• RBV
Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and = 75 kg = 1200 mg Dose of PEG+RBV group: 800 mg

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Gallipoli MRF	Greenslopes	Queensland
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane Hospital Research Foundation	Herston	Queensland
Australia	St. George Hospital	Kogarah	New South Wales
Australia	The Alfred	Melbourne	Victoria
Australia	Sir Charles Gairdner	Nedlands	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Princess Alexandria	Woollongabba	Queensland
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	University Health Network-Toronto Western Hospital	Toronto	Ontario
Canada	(G.I.R.I.) Gastrointestinal Research Institute	Vancouver	British Columbia
Canada	Toronto Digestive Disease Associates, Inc.	Vaughan	Ontario
Italy	Casa Sollievo della Sofferenza Hospital	San Giovanni Rotondo
Netherlands	Academish Medisch Centrum	Amsterdam
New Zealand	Christchurch Hospital	Chrischurch	Canterbury
New Zealand	Mercy Hospital	Dunedin	OTA
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Waikato Hospital (District Health Board)	Hamilton	Waikato
New Zealand	Wellington Hospital	Newtown	WGN
New Zealand	Tauranga Hospital	Tauranga	BOP
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
Sweden	Sahlgrenska Universitetssjukhuset, Östra Sjukhus	Göteborg
Sweden	Karolinska Universitetssjukhuset, Solna	Stockholm
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina
United States	AIDS Research Consortium of Atlanta, Inc.	Atlanta	Georgia
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Franco Felizarta, MD	Bakersfield	California
United States	Digestive Disease Associates, P.A.	Baltimore	Maryland
United States	California Liver Institute	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Pointe West Infectious Diseases	Bradenton	Florida
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Arrowhead Regional Medical Center	Colton	California
United States	SCTI Research Foundation	Coronado	California
United States	Baylor University Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Veterans Affairs Medical Center	East Orange	New Jersey
United States	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey
United States	South Denver Gastroenterology, PC	Englewood	Colorado
United States	Metropolitan Research	Fairfax	Virginia
United States	Midway Immunology & Research Center, LLC	Fort Pierce	Florida
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Gastro One	Germantown	Tennessee
United States	ID Care	Hillsborough	New Jersey
United States	Kelsey-Seybold Clinic PA	Houston	Texas
United States	Research Specialists of Texas	Houston	Texas
United States	VAMC & Baylor College	Houston	Texas
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Borland-Groover Clinic Baptist	Jacksonville	Florida
United States	eStudy Site	La Mesa	California
United States	Regional Gastroenterology Associates of Lancaster, Ltd.	Lancaster	Pennsylvania
United States	Peter J. Ruane, M.D. Inc.	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	Schleinitz Research and Gastroenterology LLC	Medford	Oregon
United States	University of Miami, School of Medicine	Miami	Florida
United States	Alabama Liver & Digestive Specialist	Montgomery	Alabama
United States	Atlantic Research Affiliates, LLC	Morristown	New Jersey
United States	Nashville Gastrointestinal Specialists Inc.	Nashville	Tennessee
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Digestive and Liver Disease Specialist, Ltd.	Norfolk	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	eStudySite	Oceanside	California
United States	Internal Medicine Specialists	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	UPMC Center For Liver Diseases	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	University of California, Davis - Health System	Sacramento	California
United States	Alamo Medical Research	San Antonio	Texas
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Research and Education, Inc.	San Diego	California
United States	University of California San Diego Medical Center	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	Southwest C.A.R.E. Center	Santa Fe	New Mexico
United States	Virginia Mason Medical Center	Seattle	Washington
United States	The Research Institute	Springfield	Massachusetts
United States	Carolinas Center for Liver Disease	Statesville	North Carolina
United States	Advanced Research Institute	Trinity	Florida
United States	Gastroenterology United of Tulsa	Tulsa	Oklahoma
United States	Digestive Health Specialists, PA	Tupelo	Mississippi
United States	University Gastroenterology	Warwick	Rhode Island
United States	South Florida Center of Gastroenterology	Wellington	Florida
United States	Digestive Health Specialists, PA	Winston-Salem	North Carolina
United States	Partners in Internal Medicine, PC	Worcester	Massachusetts
United States	University of Massachusetts, Worcester	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy,  Netherlands,  New Zealand,  Puerto Rico,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After Stopping All Study Drugs (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; < 25 IU/mL) 12 weeks after study drug cessation.	Post-treatment Week 12	No
Secondary	Number of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities		Up to 24 weeks plus 30 days following the last dose of study drug	No
Secondary	Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24)	SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation.	Post-treatment Week 24	No
Secondary	Percentage of Participants With HCV RNA < LLOQ on Treatment		Up to 12 Weeks	No
Secondary	Change From Baseline in HCV RNA		Baseline to Week 12	No
Secondary	Percentage of Participants With Virologic Failure During Treatment	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)	Baseline up to Week 24	Yes
Secondary	Percentage of Participants With Viral Relapse Following Treatment	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.	Up to Post-treatment Week 24	Yes