A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Adults

Study Overview
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Brief Summary
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This is an Open-label Phase 3 study in adults with chronic genotypes 1, 2, 3, and 4 HCV infection who are co-infected with HIV-1.

Official Title
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A Phase 3, Open-label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-infected Subjects

Conditions
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Chronic Hepatitis C, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: Sofosbuvir
* Drug: RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years with HIV-1 and chronic HCV genotype 1, 2, 3, or 4 co-infection HCV RNA > 10,000 IU/mL at screening HCV treatment history: Treatment-naive for HCV genotypes 1, 2, 3, or 4, or Treatment-experienced for HCV genotypes 2 or 3 HIV antiretroviral (ARV) criteria: On a stable, protocol-approved, HIV ARV regimen with undetectable HIV RNA for > 8 weeks prior to screening, or ARV untreated for ≥ 8 weeks prior to screening, with a CD4 T-cell count > 500 cells/mm^3 Presence or absence of cirrhosis; a liver biopsy may be required Healthy according to medical history and physical examination with the exception of HCV and HIV diagnosis Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication Exclusion Criteria: HCV genotype 1 or 4 with previous HCV treatment Poor control with HIV ARV regimen requiring a possible dose modification of therapy within 4 weeks of study medication dosing A new AIDS-defining condition diagnosed within 30 days prior to screening Prior use of any other inhibitor of the HCV NS5B polymerase History of any other clinically significant chronic liver disease Evidence of or history of decompensated liver disease Chronic hepatitis B virus (HBV) infection Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers) Chronic use of immunosuppressive agents or immunomodulatory agents Clinically relevant drug or alcohol abuse within 12 months of screening History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study or not be in the best interest of the participant in the opinion of the investigator

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: Genotype 2 treatment-naive<br>Treatment-naive (TN) participants with HIV-1 and genotype 2 HCV coinfection will receive sofosbuvir plus RBV for 12 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg tablet 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>|
| Experimental: Genotype 2/3 treatment-experienced<br>Treatment-experienced (TE) participants with HIV-1 and genotype 2 or 3 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg tablet 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>|
| Experimental: Genotype 1/3/4 treatment-naive<br>Treatment naive (TN) participants with HIV-1 and genotype 1, 3, or 4 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks. | Drug: Sofosbuvir<br>* Sofosbuvir 400 mg tablet 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>|

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 (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks following the last dose of study drug. | Posttreatment Week 12 | 
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ) 4 weeks and 24 weeks following the last dose of study drug, respectively. | Posttreatment Weeks 4 and 24 | 
| HCV RNA Change From Baseline at Week 1 |  | Baseline; Week 1 | 
| HCV RNA Change From Baseline at Week 2 |  | Baseline; Week 2 | 
| HCV RNA Change From Baseline at Week 4 |  | Baseline; Week 4 | 
| HCV RNA Change From Baseline at Week 6 |  | Baseline; Week 6 | 
| HCV RNA Change From Baseline at Week 8 |  | Baseline; Week 8 | 
| Percentage of Participants Experiencing Virologic Failure | On-treatment virologic failure was defined as either: Virologic breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Nonresponse (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment). Virologic relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period, having achieved HCV RNA < LLOQ at last on-treatment visit. | Baseline up to Posttreatment Week 24 |