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

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
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

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: Sofosbuvir
* Drug: GS-0938
* Drug: RBV
* Drug: Placebo to match sofosbuvir
* Drug: Placebo to match GS-0938


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF+RBV 12 Weeks<br>Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 12 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered 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: Ribasphere®;|
| Experimental: SOF+RBV 24 Weeks<br>Participants were randomized to receive sofosbuvir plus RBV plus placebo to match GS-0938 for 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered 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: Ribasphere®;|
| Experimental: GS-0938 Alone<br>Participants were randomized to receive GS-0938 plus placebo to match sofosbuvir for up to 24 weeks. | Drug: GS-0938<br>* GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily<br>* Other names: PSI-352938;Drug: Placebo to match sofosbuvir<br>* Placebo to match sofosbuvir administered orally once daily<br>|
| Experimental: GS-0938+SOF<br>Participants were randomized to receive GS-0938 plus sofosbuvir for up to 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily<br>* Other names: PSI-7977;Drug: GS-0938<br>* GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily<br>* Other names: PSI-352938;|
| Experimental: GS-0938+SOF+RBV<br>Participants were randomized to receive GS-0938 plus sofosbuvir plus RBV for up to 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily<br>* Other names: PSI-7977;Drug: GS-0938<br>* GS-0938 300 mg (3 × 100 mg tablets) administered orally once daily<br>* Other names: PSI-352938;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: Ribasphere®;|
| Experimental: Placebo<br>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<br>* Placebo to match sofosbuvir administered orally once daily<br>Drug: Placebo to match GS-0938<br>* Placebo to match GS-0938 administered orally once daily<br>|
| Experimental: Retreatment Group - SOF+RBV 24 Weeks<br>After discontinuing a regimen containing GS-0938, participants received sofosbuvir plus RBV for up to 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg (2 × 200 mg tablets) administered 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: Ribasphere®;|

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 | 

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