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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: RBV
* Drug: PEG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF+PEG+RBV 12 weeks<br>Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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)<br>* Other names: Copegus®;Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>* Other names: Pegasys®;|
| Experimental: SOF+PEG+RBV 24 weeks<br>Participants were randomized to receive sofosbuvir+PEG+RBV for 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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)<br>* Other names: Copegus®;Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>* Other names: Pegasys®;|
| Experimental: SOF+PEG+RBV 12 week/Rerandomization Group<br>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<br>* Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily<br>* Other names: PSI-7977;Drug: RBV<br>* 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)<br>* Other names: Copegus®;Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>* Other names: Pegasys®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Chronic Hepatitis C, Hepatitis C