Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

Phase 2

Completed

• Conditions: Chronic HCV Infection
• Interventions: Drug: SOF; Drug: LDV/SOF; Drug: RBV

• Registration Number: NCT02120300
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-18
• Study First Submitted QC: 2014-04-18
• Study First Posted: 2014-04-22
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Results First Submitted: 2016-08-16
• Status Verified: 2016-10
• Results First Submitted QC: 2016-10-13
• Last Update Submitted: 2016-10-13
• Results First Posted: 2016-12-06
• Last Update Posted: 2016-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

• Hemophilia A, B or C, or Von Willebrand's disease

• Chronic genotype 1, 2, 3 or 4 HCV infection

• HCV RNA ≥ 1000 IU/mL at screening

• Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

• Screening laboratory values within defined thresholds

• For HIV-1/HCV co-infected individuals:

  • Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
  • Stable protocol-approved ARV regimen for > 8 weeks prior to screening
  • CD4 T-cell count > 200 cells/mm^3 at screening

Read More

Exclusion Criteria

• Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

• Current or prior history of any of the following:

  • Hepatic decompensation
  • Chronic liver disease of a non-HCV etiology
  • Hepatocellular carcinoma (HCC)
  • Infection with hepatitis B virus (HBV)

• Pregnant or nursing female

• Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase

• Chronic use of systemically administered immunosuppressive agents

• For HIV-1/HCV co-infected individuals:

  • Opportunistic infection within 6 months prior to screening
  • Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SOF+RBV 12 wks GT 2	SOF	Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
SOF+RBV 24 wks GT 3	SOF	Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
SOF+RBV 12 wks GT 2	RBV	Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
LDV/SOF GT 1 or 4	LDV/SOF	Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
SOF+RBV 24 wks GT 3	RBV	Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 24 weeks
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	Posttreatment Week 4	SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)	Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24	Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24	Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24
Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24	Virologic failure was defined as: * On-treatment virologic failure: * 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; * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only)	Baseline; Weeks 12, 24, and Posttreatment Week 12