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

Chronic HCV Infection Clinical Trial

Official title:

A Phase 2b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02120300
• Other study ID #: GS-US-334-1274
• Status: Completed
• Phase: Phase 2
• First received: April 18, 2014
• Last updated: August 25, 2015
• Start date: April 2014
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) for participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) for 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 participants:

• 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

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 NS5A or the NS5B polymerase

• Chronic use of systemically administered immunosuppressive agents

• For HIV-1/HCV co-infected subjects:

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Chronic HCV Infection
• Hemostatic Disorders
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• LDV/SOF
Ledipasvir 90 mg /sofosbuvir 400 mg (LDV/SOF) FDC tablet administered orally
• SOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12)	SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.	Posttreatment Week 12	No
Primary	Incidence of adverse events leading to permanent discontinuation of study drug(s)		Up to 24 weeks	No
Secondary	Proportion of participants with sustained virologic response (SVR) at 4 weeks after discontinuation of therapy (SVR4)	SVR4 is defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug.	Posttreatment Week 4	No
Secondary	Proportion of participants with HCV RNA < LLOQ on treatment		Up to 24 weeks	No
Secondary	HCV RNA change from baseline		Up to 24 weeks	No
Secondary	Proportion of participants with virologic failure	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	Up to Posttreatment Week 12	No
Secondary	For HIV-1/HCV co-infected participants, the proportion of participants that maintain HIV-1 RNA < 50 copies/mL while on HCV treatment		Up to 24 weeks	No
Secondary	For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at the end of treatment		Up to 24 weeks	No
Secondary	For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at posttreatment Week 12		Up to Posttreatment Week 12	No