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

Phase 3

Completed

• Conditions: Human Immunodeficiency Virus; Chronic Hepatitis C
• Interventions: Drug: Sofosbuvir; Drug: RBV

• Registration Number: NCT01783678
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-01-31
• Study First Submitted QC: 2013-02-01
• Study First Posted: 2013-02-05
• Primary Completion: 2014-04
• Study Completion: 2014-07
• Status Verified: 2015-04
• Results First Submitted: 2015-04-15
• Results First Submitted QC: 2015-04-15
• Last Update Submitted: 2015-04-15
• Results First Posted: 2015-04-30
• Last Update Posted: 2015-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 275

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Genotype 2 treatment-naive	RBV	Treatment-naive (TN) participants with HIV-1 and genotype 2 HCV coinfection will receive sofosbuvir plus RBV for 12 weeks.
Genotype 2 treatment-naive	Sofosbuvir	Treatment-naive (TN) participants with HIV-1 and genotype 2 HCV coinfection will receive sofosbuvir plus RBV for 12 weeks.
Genotype 2/3 treatment-experienced	Sofosbuvir	Treatment-experienced (TE) participants with HIV-1 and genotype 2 or 3 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks.
Genotype 2/3 treatment-experienced	RBV	Treatment-experienced (TE) participants with HIV-1 and genotype 2 or 3 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks.
Genotype 1/3/4 treatment-naive	Sofosbuvir	Treatment naive (TN) participants with HIV-1 and genotype 1, 3, or 4 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks.
Genotype 1/3/4 treatment-naive	RBV	Treatment naive (TN) participants with HIV-1 and genotype 1, 3, or 4 HCV co-infection will receive sofosbuvir plus RBV for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	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.
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)	Up to 24 weeks	The percentage of participants permanently discontinuing any study drug due to an adverse event was summarized.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	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.
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	Baseline up to Posttreatment Week 24	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."