Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01701401
First received: October 2, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate the safety, tolerability and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.


Condition Intervention Phase
Chronic Hepatitis C Virus
Drug: LDV/SOF
Drug: RBV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with sustained virologic response (SVR) 12 weeks after discontinuation of study drug [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 is defined as HCV RNA level < the lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.

  • Incidence of any AE leading to permanent discontinuation of study [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with SVR at 4 and 24 weeks after discontinuation of study drug [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
    SVR4 and SVR24 are is defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.

  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in HCV RNA [ Time Frame: Baseline to 8 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to posttreatment Week 24 ] [ Designated as safety issue: No ]

    Virologic failure is defined as:

    • Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Rebound: > 1 log10IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment, OR Relapse: HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement


Enrollment: 870
Study Start Date: September 2012
Study Completion Date: April 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDV/SOF 24 weeks
Participants will receive LDV/SOF for 24 weeks
Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed dose combination (FDC) tablet administered orally once daily
Other Names:
  • Sofosbuvir is also known as GS-7977, PSI-7977, or Sovaldi®
  • Ledipasvir is also known as GS-5885.
Experimental: LDV/SOF+RBV 24 weeks
Participants will receive LDV/SOF+RBV for 24 weeks.
Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed dose combination (FDC) tablet administered orally once daily
Other Names:
  • Sofosbuvir is also known as GS-7977, PSI-7977, or Sovaldi®
  • Ledipasvir is also known as GS-5885.
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: LDV/SOF 12 weeks
Participants will receive LDV/SOF for 12 weeks
Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed dose combination (FDC) tablet administered orally once daily
Other Names:
  • Sofosbuvir is also known as GS-7977, PSI-7977, or Sovaldi®
  • Ledipasvir is also known as GS-5885.
Experimental: LDV/SOF+RBV 12 weeks
Participants will receive LDV/SOF+RBV for 12 weeks.
Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed dose combination (FDC) tablet administered orally once daily
Other Names:
  • Sofosbuvir is also known as GS-7977, PSI-7977, or Sovaldi®
  • Ledipasvir is also known as GS-5885.
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18, with chronic genotype 1 HCV infection
  • HCV treatment-naive
  • HCV RNA > 10,000 IU/mL at Screening
  • Cirrhosis determination; a liver biopsy may be required
  • Screening laboratory values within defined thresholds
  • Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

  • Pregnant or nursing female or male with pregnant female partner
  • Co-infection with HIV or HBV
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
  • Chronic use of systemic immunosuppressive agents
  • History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01701401

  Show 88 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jenny Yang, Pharm D Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01701401     History of Changes
Other Study ID Numbers: GS-US-337-0102, 2012-003387-43
Study First Received: October 2, 2012
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Italy: The Italian Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Gilead Sciences:
HCV genotype 1 (GT-1)
HCV
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
GS-7977
GS-5885
Ribavirin
Open Label
Sofosbuvir
Additional relevant MeSH terms:
Hepatitis
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Molecular Mechanisms of Pharmacological Action
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014