SOF (Sovaldi®) +RBV for 16 or 24 Weeks and SOF+RBV+Peg-IFN for 12 Weeks in Adults With Genotype 2 or 3 Chronic HCV Infection

A Phase 3B Randomized, Open-Label, Multi-Center Trial Assessing Sofosbuvir + Ribavirin for 16 or 24 Weeks and Sofosbuvir + Pegylated Interferon + Ribavirin for 12 Weeks in Subjects With Genotype 2 or 3 Chronic HCV Infection.

This study will assess the efficacy, safety, and tolerability of 16 or 24 weeks of sofosbuvir (Sovaldi®; SOF) + ribavirin (RBV), and 12 weeks of SOF+RBV+ pegylated interferon (Peg-IFN) in treatment-naive and treatment-experienced adults with chronic genotype 3 hepatitis C virus (HCV) infection, and treatment-experienced adults with cirrhosis and chronic genotype 2 HCV infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: SOF; Drug: RBV; Drug: Peg-IFN

• Study Type: Interventional
• Enrollment (Actual): 601
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
    • Kogarah, New South Wales, Australia, 2217
    • Westmead, New South Wales, Australia, 2145
  • Queensland
    • Brisbane, Queensland, Australia, 4029
    • Greenslopes, Queensland, Australia, 4120
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Adelaide, South Australia, Australia, 5000
  • Victoria
    • Clayton, Victoria, Australia, 3168
    • Fitzroy, Victoria, Australia, 3065
    • Heidelberg, Victoria, Australia, 3084
    • Melbourne, Victoria, Australia, 3004
  • Western Australia
    • Nedlands Perth, Western Australia, Australia, 6009
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V6Z 2K5
    • Vancouver, British Columbia, Canada, V6Z 2C7
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
    • London, Ontario, Canada, N6A 5A5
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M5T 2S8
    • Toronto, Ontario, Canada, M6H 3M1
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
    • Québec, Quebec, Canada, G1V 4G2
• New Zealand
  • Wellington, New Zealand, 6021
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
    • Grafton, Auckland, New Zealand, 1023
  • Chatham Islands
    • Christchurch, Chatham Islands, New Zealand, 8011
  • Waikato
    • Hamilton, Waikato, New Zealand, 3204
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
  • Bradford, United Kingdom, BD9 6RJ
  • Dundee, United Kingdom, DD1 9SY
  • Edinburgh, United Kingdom, EH16 4SA
  • Edinburgh, United Kingdom, EH4 2XU
  • Frimley, United Kingdom, GU46 6HU
  • Glasgow, United Kingdom, G12 0YN
  • Glasgow, United Kingdom, G4 0SF
  • Leeds, United Kingdom, LS9 7TF
  • Liverpool, United Kingdom, L7 8XP
  • London, United Kingdom, NW3 2QG
  • London, United Kingdom, SW10 9NH
  • Manchester, United Kingdom, M85RB
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
  • Nottingham, United Kingdom, NG7 2UH
  • Oxford, United Kingdom, OX3 9DU
  • Plymouth, United Kingdom, PL6 8DH
  • Portsmouth, United Kingdom, PO6 3LY
  • Southampton, United Kingdom, SO16 6YD
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2TH
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
  • LN
    • London, LN, United Kingdom, E1 1BB
    • London, LN, United Kingdom, SE5 9RS
    • London, LN, United Kingdom, SW17 ORE
    • London, LN, United Kingdom, W2 1NY
• United States
  • California
    • Riverside, California, United States, 92501
    • San Diego, California, United States, 92123
    • San Francisco, California, United States, 94115
  • Colorado
    • Aurora, Colorado, United States, 80045
    • Englewood, Colorado, United States, 80113
  • Florida
    • Miami, Florida, United States, 33136
    • Wellington, Florida, United States, 33414
  • Georgia
    • Marietta, Georgia, United States, 30060
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • Michigan
    • Novi, Michigan, United States, 48377
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
    • Newark, New Jersey, United States, 07102
  • New York
    • Binghamton, New York, United States, 13903
    • New York, New York, United States, 10021
  • Tennessee
    • Germantown, Tennessee, United States, 38138
    • Nashville, Tennessee, United States, 37211
    • Nashville, Tennessee, United States, 37212-1610
  • Texas
    • Arlington, Texas, United States, 76012
    • Austin, Texas, United States, 78705
  • Virginia
    • Norfolk, Virginia, United States, 23502
  • Washington
    • Seattle, Washington, United States, 98101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Male or female, age greater than or equal to 18 years.
• Confirmed chronic HCV infection.
• Subjects will have cirrhosis status assessment; liver biopsy may be required.
• Genotype 2 subjects must have cirrhosis of the liver to be eligible.
• Treatment-naive or prior treatment failure to ≥12 weeks of an interferon- based regimen that was not discontinued prematurely due to an adverse event
• Infection with HCV genotype 2 or 3 as determined at Screening
• Body mass index (BMI) greater than or equal to 18 kg/m^2
• Screening laboratory values within predefined thresholds.
• Liver imaging (e.g., ultrasound) within 6 months of Baseline/Day 1 is required in cirrhotic patients to exclude hepatocellular carcinoma (HCC). In the event of intrahepatic lesions, triple phase CT scan or MRI should be performed to exclude HCC.
• Subject must be of generally good health as determined by the Investigator.

Key Exclusion Criteria:

• Prior use of any other inhibitor of the HCV nonstructural protein (NS)5B polymerase
• Pregnant or nursing female or male with pregnant female partner
• History of any other clinically significant chronic liver disease.
• HIV or chronic hepatitis B virus (HBV) infection.
• Malignancy with the exception of certain resolved skin cancers.
• Chronic use of systemically administered immunosuppressive agents.
• Clinically-relevant drug or alcohol abuse.
• History of solid organ transplantation.
• Current or prior history of clinical hepatic decompensation.
• History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol.
• Known hypersensitivity to interferon, RBV, the study investigational medicinal product, the metabolites, or formulation excipients.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOF+RBV 16 weeks; SOF+RBV for 16 weeks	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: SOF+RBV 24 weeks; SOF+RBV for 24 weeks	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: SOF+RBV+Peg-IFN 12 weeks; SOF+RBV+Peg-IFN for 12 weeks	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: Peg-IFN; 180 µg administered via subcutaneous injection once weekly
Experimental: Retreatment Substudy; Participants from the SOF+RBV arms (16 weeks or 24 weeks) who experienced virologic failure on treatment, or during the posttreatment period at or before Posttreatment Week 24 may be eligible to enroll into the Retreatment Substudy to receive SOF+RBV+Peg-IFN for 12 weeks.	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: Peg-IFN; 180 µg administered via subcutaneous injection once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.	Posttreatment Weeks 4 and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, and 12		Baseline; Weeks 1, 2, 4, 8, and 12
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24		Weeks 1, 2, 4, 8, 12, 16, 20, and 24
HCV RNA at Weeks 1, 2, 4, 8, and 12		Weeks 1, 2, 4, 8, and 12
Percentage of Participants Experiencing On-Treatment Virologic Failure	On-treatment virologic failure was defined as: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or; Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or; Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)	Up to 24 weeks
Percentage of Participants Experiencing Viral Relapse	Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.	Up to Posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Foster GR, Pianko S, Brown A, Forton D, Nahass RG, George J, Barnes E, Brainard DM, Massetto B, Lin M, Han B, McHutchison JG, Subramanian GM, Cooper C, Agarwal K; BOSON Study Group. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology. 2015 Nov;149(6):1462-70. doi: 10.1053/j.gastro.2015.07.043. Epub 2015 Aug 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2013
• Primary Completion (Actual): January 7, 2015
• Study Completion (Actual): July 7, 2016

Study Registration Dates

• First Submitted: October 10, 2013
• First Submitted That Met QC Criteria: October 10, 2013
• First Posted (Estimate): October 14, 2013

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: May 24, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: GS-7977; 7977; PSI-7977; Sofosbuvir (SOF); Pegylated Interferon (Peg-IFN); Ribavirin (RBV)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: GS-US-334-0153; 2013-002641-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No