Safety Study of Regimens of Sofosbuvir, GS-0938, and Ribavirin in Patients With Chronic Hepatitis C Infection (QUANTUM)

QUANTUM: An International, Multi-center, Blinded, Randomized Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Administration of Regimens Containing PSI-352938, PSI-7977, and Ribavirin in Patients With Chronic Hepatitis C Virus (HCV) Infection

This study was designed to assess the safety and efficacy of multiple interferon-free treatment regimens of sofosbuvir (Sovaldi™; GS-7977; PSI-7977) and GS-0938 (PSI-352938) alone and in combination, with and without ribavirin (RBV). Each regimen was to be evaluated over 12 and 24 weeks to identify the optimal duration of therapy to maximize the benefit (sustained virologic response [SVR]) versus risk (safety and resistance).

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: RBV; Drug: Sofosbuvir; Drug: GS-0938; Drug: Placebo to match sofosbuvir; Drug: Placebo to match GS-0938

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion de Diego
  • San Juan, Puerto Rico, 00909
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver & Digestive Specialists
  • California
    • Bakersfield, California, United States, 93301
    • Coronado, California, United States, 92118
    • La Mesa, California, United States, 91942
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90048
      • CLI
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center
    • San Diego, California, United States, 92120
      • eStudy Site
    • San Diego, California, United States, 92193
      • Medical Associates Research Group
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80220
    • Engelwood, Colorado, United States, 80113
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
  • Florida
    • Deland, Florida, United States, 32720
      • Avail Clinical Research
    • Gainesville, Florida, United States, 32610
      • University Of Florida Hepatology
    • Miami, Florida, United States, 33136
      • University of Miami Center for Liver Diseases
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Trinity, Florida, United States, 34655
      • Advanced Research Institute
    • Wellington, Florida, United States, 33414
      • South Florida Center of Gastroenterology
  • Georgia
    • Atlanta, Georgia, United States, 30308
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Marietta, Georgia, United States, 30060
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Digestive Health Services
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Baltimore, Maryland, United States, 21229
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • Concorde Medical Group
  • North Carolina
    • Ashville, North Carolina, United States, 28801
      • Ashville Gastroenterology Associates
    • Statesville, North Carolina, United States, 28677
      • Carolina'S Center For Liver Disease
    • Winston-Salem, North Carolina, United States, 27103
      • Digestive Health Specialists
  • Ohio
    • Cincinnati, Ohio, United States
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37211
      • Nashville Gastrointestinal Specialists
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic HCV-infection
• Naive to all HCV antiviral treatment
• Otherwise healthy patients

Exclusion Criteria:

• Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab
• History of any other clinically significant chronic liver disease
• Medical history which the investigator considers the patient unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOF+RBV 12 Weeks; Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 12 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Ribasphere®; Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: GS-7977; PSI-7977; Sovaldi™
Experimental: SOF+RBV 24 Weeks; Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 24 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Ribasphere®; Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: GS-7977; PSI-7977; Sovaldi™
Experimental: GS-0938 Alone; Participants were randomized to receive GS-0938 plus placebo to match sofosbuvir for up to 24 weeks.	Drug: GS-0938; GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily; Other Names: PSI-352938; Drug: Placebo to match sofosbuvir; Placebo to match sofosbuvir administered orally once daily
Experimental: GS-0938+SOF; Participants were randomized to receive GS-0938 plus sofosbuvir for up to 24 weeks.	Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: GS-7977; PSI-7977; Sovaldi™; Drug: GS-0938; GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily; Other Names: PSI-352938
Experimental: GS-0938+SOF+RBV; Participants were randomized to receive GS-0938 plus sofosbuvir plus RBV for up to 24 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Ribasphere®; Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: GS-7977; PSI-7977; Sovaldi™; Drug: GS-0938; GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily; Other Names: PSI-352938
Experimental: Placebo; Deferred start group: Participants were randomized to receive placebo to match GS-0938 plus placebo to match sofosbuvir for 24 Weeks.	Drug: Placebo to match sofosbuvir; Placebo to match sofosbuvir administered orally once daily; Drug: Placebo to match GS-0938; Placebo to match GS-0938 administered orally once daily
Experimental: Retreatment Group - SOF+RBV 24 Weeks; After discontinuing a regimen containing GS-0938, participants received sofosbuvir plus RBV for up to 24 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Ribasphere®; Drug: Sofosbuvir; Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily; Other Names: GS-7977; PSI-7977; Sovaldi™

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 study drug (SVR12)	SVR12 was defined as HCV RNA < LLOQ 12 weeks after the last dose of all study drugs.	Post-treatment Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Adverse Events	Adverse events (AEs) were summarized across the participant population. A participant was counted once if they had a qualifying event.	Baseline to Week 24 plus 30 days
Change from baseline in HCV RNA		Baseline to Week 12
Percentage of Participants With HCV RNA < LLOQ during treatment		Baseline to Week 12
Percentage of Participants With ALT Normalization	ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at a subsequent visit.	Baseline to post-treatment Week 4
Percentage of participants with SVR at 4 and 24 weeks after discontinuation of study drug (SVR4; SVR24)	SVR4 and SVR24 was defined as HCV RNA < LLOQ 4 and 24 weeks after the last dose of all study drugs, respectively.	Post-treatment Weeks 4 and 24
Percentage of Participants Who Developed Resistance to Sofosbuvir		Baseline to Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Quintiles, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: September 9, 2011
• First Submitted That Met QC Criteria: September 13, 2011
• First Posted (Estimate): September 15, 2011

Study Record Updates

• Last Update Posted (Estimate): February 6, 2014
• Last Update Submitted That Met QC Criteria: January 7, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; Chronic
• 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; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Sofosbuvir; Ribavirin
• Other Study ID Numbers: P2938-0721