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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01329978
First received: March 30, 2011
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Sofosbuvir
Drug: RBV
Drug: PEG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24) [ Time Frame: Post-treatment Week 24 ] [ Designated as safety issue: No ]
    SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.

  • Percentage of Participants Who Experienced Adverse Events [ Time Frame: Baseline (Day 1) to post-treatment Day 30 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12) [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.

  • Change in HCV RNA at Week 2 [ Time Frame: Baseline (Day 1) to Week 2 ] [ Designated as safety issue: No ]
  • Change in HCV RNA at Week 4 [ Time Frame: Baseline (Day 1) to Week 4 ] [ Designated as safety issue: No ]
  • Change in HCV RNA at Week 8 [ Time Frame: Baseline (Day 1) to Week 8 ] [ Designated as safety issue: No ]
  • Change in HCV RNA at Week 12 [ Time Frame: Baseline (Day 1) to Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LOD at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA Below < LOD at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA Below < LOD at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA Below < LOD at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA Below < LOD at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With ALT Normalization at Week 12 [ Time Frame: Baseline (Day 1) to Week 12 ] [ Designated as safety issue: No ]
    ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.

  • Percentage of Participants With ALT Normalization at Week 24 [ Time Frame: Baseline (Day 1) to Week 24 ] [ Designated as safety issue: No ]
    ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.

  • Percentage of Participants With ALT Normalization at Post-treatment Week 4 [ Time Frame: Baseline (Day 1) to Post-treatment Week 4 ] [ Designated as safety issue: No ]
    ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.

  • Percentage of Participants With Virologic Failure During Treatment [ Time Frame: Baseline (Day 1) to Week 24 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse). [ Time Frame: End of treatment to Post-treatment Week 24 ] [ Designated as safety issue: No ]
    Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.


Enrollment: 332
Study Start Date: March 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOF+PEG+RBV 12 weeks
Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks.
Drug: Sofosbuvir
Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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 Name: Copegus®
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Other Name: Pegasys®
Experimental: SOF+PEG+RBV 24 weeks
Participants were randomized to receive sofosbuvir+PEG+RBV for 24 weeks.
Drug: Sofosbuvir
Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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 Name: Copegus®
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Other Name: Pegasys®
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: Sofosbuvir
Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
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 Name: Copegus®
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Other Name: Pegasys®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01329978

  Show 46 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Robert H. Hyland, DPhil Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01329978     History of Changes
Other Study ID Numbers: P7977-0724
Study First Received: March 30, 2011
Results First Received: January 6, 2014
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C
HCV
Chronic Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferons
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014