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

Hepatitis C Virus Infection Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02600351
• Other study ID #: GS-US-337-1746
• Status: Terminated
• Phase: Phase 3
• Start date: November 11, 2015
• Est. completion date: May 29, 2017

Study information

• Verified date: August 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 87
• Est. completion date: May 29, 2017
• Est. primary completion date: March 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C Virus Infection
• Virus Diseases

Intervention

Drug:
• LDV/SOF
90/400 mg FDC tablet administered orally once daily
• RBV
Tablets administered orally in a divided daily dose according to weight-based dosing recommendations (< 75 kg = 1000 mg and = 75 kg = 1200 mg)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (4)

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 Infecti

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-NS

Tam E, Luetkemeyer AF, Mantry PS, Satapathy SK, Ghali P, Kang M, Haubrich R, Shen X, Ni L, Camus G, Copans A, Rossaro L, Guyer B, Brown RS Jr; RESCUE and ACTG A5348 study investigators. Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvi — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After Cessation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Primary	Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event		Up to 24 weeks
Secondary	Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.	Posttreatment Weeks 4 and 24
Secondary	Percentage of Participants With Viral Breakthrough	Viral breakthrough was defined as HCV RNA = LLOQ after having previously had HCV RNA < LLOQ while receiving treatment.	Up to 24 weeks
Secondary	Percentage of Participants With Viral Relapse	Viral relapse was defined as confirmed HCV RNA = LLOQ during the posttreatment period having achieved HCV RNA	Up to Posttreatment Week 24
Secondary	Number of Participants With Emerging Resistance	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.	Up to Posttreatment Week 24