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Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Participants Who Have Failed Prior Treatment With Sofosbuvir-based Therapies

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ClinicalTrials.gov Identifier: NCT02600351
Recruitment Status : Terminated (Due to lack of feasibility of enrolling participants, the study was terminated early.)
First Posted : November 9, 2015
Results First Posted : April 11, 2018
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) for 12 weeks with or without ribavirin (RBV) in participants without cirrhosis, and LDV/SOF FDC for 12 weeks with RBV or LDV/SOF FDC for 24 weeks without RBV in participants with cirrhosis.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: LDV/SOF Drug: RBV Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Subjects Who Have Failed Prior Treatment With Sofosbuvir-based Therapies
Actual Study Start Date : November 11, 2015
Actual Primary Completion Date : March 21, 2017
Actual Study Completion Date : May 29, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LDV/SOF 12 weeks, without cirrhosis
LDV/SOF for 12 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Experimental: LDV/SOF + RBV 12 weeks, without cirrhosis
LDV/SOF + RBV for 12 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Drug: RBV
Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Experimental: LDV/SOF + RBV 12 weeks, with compensated cirrhosis
LDV/SOF + RBV for 12 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Drug: RBV
Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Experimental: LDV/SOF 24 weeks, with compensated cirrhosis
LDV/SOF for 24 weeks
Drug: LDV/SOF
90/400 mg FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977




Primary Outcome Measures :
  1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Cessation of Therapy (SVR12) [ Time Frame: 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.

  2. Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :
  1. Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.

  2. Percentage of Participants With Viral Breakthrough [ Time Frame: Up to 24 weeks ]
    Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.

  3. Percentage of Participants With Viral Relapse [ Time Frame: Up to Posttreatment Week 24 ]
    Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA <LLOQ at last on-treatment visit.

  4. Number of Participants With Emerging Resistance [ Time Frame: Up to Posttreatment Week 24 ]
    The full-length NS3, NS5A, and NS5B coding regions were deep sequenced at pretreatment (baseline) for all participants included in the Full Analysis Set, and at posttreatment for all participants who relapsed.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • HCV RNA > 15 IU/mL at screening
  • HCV genotype 1 or 4
  • Chronic HCV infection (≥ 6 months)
  • Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
  • Cirrhotic and non-cirrhotic as determined by standard methods
  • Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Key Exclusion Criteria:

  • Prior exposure to approved or experimental non-structural protein (NS5A) inhibitors
  • Prior exposure to nucleos(t)ide polymerase inhibitors, other than SOF
  • Pregnant or nursing female or male with pregnant female partner
  • Coinfection with HIV or hepatitis B virus
  • Current or prior history of clinical hepatic decompensation
  • Hepatocellular carcinoma 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 individual's treatment, assessment or compliance with the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02600351


  Show 42 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Original  [PDF] March 13, 2015
Study Protocol: Amendment 1  [PDF] June 12, 2015
Study Protocol: Amendment 2  [PDF] July 23, 2015
Statistical Analysis Plan  [PDF] March 28, 2017


Publications of Results:
Tam E, Brown RS, Satapathy S, Shen X, Camus G, Copans A, et al. Efficacy and Safety of Ledipasvir/Sofosbuvir (LDV/SOF), with or without Ribavirin (RBV), for Treatment of HCV-mono and HIV/HCV Co-infected Patients Who Have Failed Prior Treatment with Non-NS5A, SOF-based Therapies [Poster THU-265]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
Tam E, Mantry PS, Satapathy SK, Ghali P, Shen X, Han LL, et al. A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir (LDV/SOF), with or without Ribavirin (RBV), in HCV Infected Subjects Who Have Failed Prior Treatment with Non-NS5A, SOF-based Therapies (RESCUE) [Poster PP0217]. Asian Pacific Association for the Study of the Liver (APASL); 2017 15-19 February; Shanghai, China.
Tam E, Brown RS, Satapathy S, Camus G, Copans A, Rossaro L, et al. Ledipasvir/Sofosbuvir ± Ribavirin in HCV and HIV/HCV Prior SOF-based Virologic Failures (RESCUE and ACTG A5348 Studies) [Poster 568LB]. Conference on Retroviruses and Opportunistic Infections (CROI); 2017 13-16 February; Seattle, WA.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02600351     History of Changes
Other Study ID Numbers: GS-US-337-1746
First Posted: November 9, 2015    Key Record Dates
Results First Posted: April 11, 2018
Last Update Posted: November 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Gilead Sciences:
Hepatitis C Virus (HCV)
Ledipasvir/Sofosbuvir
Ribavirin
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents