Sofosbuvir With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6 (ATOMIC)

The ATOMIC Study: A Multicenter, Open-label, Randomized, Duration Finding Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Pegylated Interferon and Ribavirin in Treatment-Naive Patients With Chronic HCV Infection Genotype 1,4, 5, or 6

The purpose of this study is to assess the safety, tolerability, and efficacy of sofosbuvir (GS-7977; PSI-7977) administered in combination with pegylated interferon and ribavirin (PEG/RBV) in treatment-naive patients with HCV genotypes 1,4,5,6, or indeterminate genotype.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: RBV; Drug: PEG; Drug: Sofosbuvir

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico
  • San Juan, Puerto Rico
    • Fundacion De Investigacion de Diego
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver and Digestive Specialist
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Clopton Clinic
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Coronado, California, United States, 92118
      • Southern California Liver Centers
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Oceanside, California, United States, 92056
      • eStudy Site
    • San Diego, California, United States, 92114
      • Desta Digestive Disease Medical Center
    • San Diego, California, United States, 92123
      • Medical Associates Reseach Group
    • San Diego, California, United States, 92154
      • Kaiser Permanente Hepatology Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Transplant Center and Hepatology Clinic
    • Englewood, Colorado, United States, 80110
      • South Denver Gastreoenterology
  • Florida
    • Bradenton, Florida, United States, 34209
      • Pointe West Infectious Disease
    • Deland, Florida, United States, 32720
      • Avail Clinical Research
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • 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 Gastroenterology Associates
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Reisterstown, Maryland, United States, 21136
      • Clinical Associates Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deconess Medical Center
    • Worcester, Massachusetts, United States, 01655
      • U Mass Memorial Medical Center
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • St. Louis University Gastroenterology and Hepatology Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Science Center
  • New York
    • Manhasset, New York, United States, 11303
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
    • New York, New York, United States, 10016
      • Concorde Medical Group
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates
    • Durham, North Carolina, United States
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Columbia Gastroenterology Associates
  • Texas
    • Arlington, Texas, United States, 76012
      • North Texas Research Institute
    • Austin, Texas, United States, 78705
      • Central Texas Cinical Research
    • Dallas, Texas, United States, 75246
      • Baylor University
    • Houston, Texas, United States, 77030
      • Baylor/ St. Luke's Advanced Liver Therapy
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialist
  • 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:

• Males and females with Chronic Hepatitis C (HCV) Genotype 1,4,5,6, or indeterminate
• Naive to previous HCV treatment

Exclusion Criteria:

• Positive for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab
• History of any other clinically significant chronic liver disease

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOF+PEG+RBV 12 weeks; Participants were randomized to receive sofosbuvir+PEG+RBV 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: Copegus®; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®; Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977
Experimental: SOF+PEG+RBV 24 weeks; Participants were randomized to receive sofosbuvir+PEG+RBV 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: Copegus®; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®; Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977
Experimental: SOF+PEG+RBV 12 week/Rerandomization Group; Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks, then were rerandomized to receive sofosbuvir only or sofosbuvir+RBV for 12 additional 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: Copegus®; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®; Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)	SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.	Post-treatment Week 24
Percentage of Participants Who Experienced Adverse Events	Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.	Baseline (Day 1) to post-treatment Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)	SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.	Post-treatment Week 12
Change in HCV RNA at Week 2		Baseline (Day 1) to Week 2
Change in HCV RNA at Week 4		Baseline (Day 1) to Week 4
Change in HCV RNA at Week 8		Baseline (Day 1) to Week 8
Change in HCV RNA at Week 12		Baseline (Day 1) to Week 12
Percentage of Participants With HCV RNA < LOD at Week 2		Week 2
Percentage of Participants With HCV RNA Below < LOD at Week 4		Week 4
Percentage of Participants With HCV RNA Below < LOD at Week 8		Week 8
Percentage of Participants With HCV RNA Below < LOD at Week 12		Week 12
Percentage of Participants With HCV RNA Below < LOD at Week 24		Week 24
Percentage of Participants With ALT Normalization at Week 12	ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.	Baseline (Day 1) to Week 12
Percentage of Participants With ALT Normalization at Week 24	ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.	Baseline (Day 1) to Week 24
Percentage of Participants With ALT Normalization at Post-treatment Week 4	ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.	Baseline (Day 1) to Post-treatment Week 4
Percentage of Participants With Virologic Failure During Treatment	Virologic failure was defined as either; HCV RNA ≥ 15 IU/mL after having previously had HCV RNA < 15 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement (ie, breakthrough);; > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement (ie, rebound);or; HCV RNA persistently ≥ 15 IU/mL through 8 weeks of treatment (ie, nonresponse) Baseline was Day 1 for all groups.	Baseline (Day 1) to Week 24
Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).	Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.	End of treatment to Post-treatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5. Erratum In: Lancet. 2014 Mar 8;383(9920):870.
• Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, DeMicco M, Bernstein DE, Afdhal N, Vierling JM, Gordon SC, Anderson JK, Hyland RH, Dvory-Sobol H, An D, Hindes RG, Albanis E, Symonds WT, Berrey MM, Nelson DR, Jacobson IM. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet. 2013 Jun 15;381(9883):2100-7. doi: 10.1016/S0140-6736(13)60247-0. Epub 2013 Mar 15.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 30, 2011
• First Submitted That Met QC Criteria: April 4, 2011
• First Posted (Estimate): April 6, 2011

Study Record Updates

• Last Update Posted (Estimate): May 26, 2014
• Last Update Submitted That Met QC Criteria: April 24, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: HCV; Chronic Hepatitis C; Hepatitis C
• 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; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: P7977-0724