Pilot Study to Assess Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-dose Combination in Treatment Experienced Subjects With Hepatitis C Virus (HCV) Genotype 1 - HIV Co-infection

NCT02125500 | Completed Phase 2 DMC

• 1 other identifier: ANRS HC31 SOFTRIH
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Aim of the study is to assess the efficacy and safety of 24 weeks of oral Sofosbuvir/Ledipasvir fixed-dose combination (FDC) in subjects with HCV genotype 1 infection and HIV co-infection, who have previously failed a NS3/4A protease inhibitor plus Pegylated interferon /ribavirin regimen or stopped prematurely their treatment for intolerance.

Conditions

Viral Hepatitis C; HIV

Keywords

HCV/HIV coinfection; HCV genotype 1

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response 12 weeks after discontinuation of therapy (SVR12), i.e. at week 36.

  12 weeks post-treatment

Secondary Outcomes (8)

• Adverse clinical and biological events that occur during the treatment and up to 24 weeks after the end of the treatment

  up to 24 weeks after the end of the treatment

• Number and causes of poor adherence and treatment interruptions

  at 1,2,3,4,8,12,16, 20, 24 weeks during treatment, 4, 8,14,18,24 weeks after treatment discontinuationeeks after discontinuation of drugs

• SVR rate 24 weeks (i.e. W48) after the end of treatment and according to the HCV sub-type

  Week 48

• Number of patients with HCV resistance mutations to Sofosbuvir and/or Ledipasvir

  from Day(D)0 to Week (W)24

• HCV viral load

  at Day 0, Week 1, 2, 4, 8, 12, 16, 20, week 24, and 4, 8, 12, 18 and 24 weeks after the end of the treatment

Study Arms (1)

Sofosbuvir/Ledipasvir

EXPERIMENTAL

Non-cirrhotic patients will receive SOF/LDV Fixed Dose Combination (FDC) for 12 weeks. Cirrhotic patients will receive SOF/LDV Fixed Dose Combination (FDC) for 24 weeks.

Drug: Sofosbuvir/Ledipasvir fixed dose

Interventions

Sofosbuvir/Ledipasvir fixed dose DRUG

SOF 400 mg/LDV 90 mg FDC tablet administered orally once daily

Also known as: Sofosbuvir is also known as GS-7977 or PSI-7977., Ledipasvir is also known as GS-5885.

Sofosbuvir/Ledipasvir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed HIV infection
• Infection with HCV genotype 1 only, confirmed at screen visit, with a HCV-RNA ≥ 1000 InternationalUnit(IU)/mL at screen visit
• Treatment-experienced subjects with:
• previous virological failure to tritherapy with Peginterferon/Ribavirin and protease inhibitor,
• or premature discontinuation of previous tritherapy with Peginterferon/Ribavirin and protease inhibitor due to intolerance to Peginterferon or protease inhibitor
• Anti-HCV treatment stopped for at least the last 3 months
• Patients on a stable (for more than 1 month) antiretroviral treatment consisting of an emtricitabine/tenofovir or lamivudine/tenofovir standard of care backbone plus efavirenz or raltegravir or rilpivirine or enfuvirtide. Alternative combinations of the above listed medications may be allowed.
• Dendritic cells 4 \> 100/mm3 and \> 15% at screen visit
• HIV-RNA \< 50cp/ml for more than 3 months at screen visit
• Any liver fibrosis grade, with the assessment of the presence or not of cirrhosis at screening, cirrhosis being defined as a METAVIR score of F4 on the liver puncture biopsy and/or with hepatic impulse elastometry ≥ 14,5 kilopascal (kPa):
• Previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4),
• and/or significant liver biopsy (cumulative length ≥ 15mm or ≥ 5 portal spaces), within the past 18 months
• and/or significant and reliable liver stiffness assessment (Fibroscan®) within the past 6 months (at least 10 measures with IQR less than 30% of the median value and a success rate of at least 70%).
• Female patients with child-bearing potential, and their heterosexual partners must use adequate contraception from the date of screening until 90 days after administration of the last dose of study drug. Male participants must agree to consistently and correctly use a condom, while their female partner must use adequate contraception from the date of screening until 90 days after administration of the last dose of study drug
• Body weight ≥40 kg and ≤125 kg

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (1)

Centre de Méthodologie et de Gestion de Rennes

Rennes, France

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; ledipasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Eric Rosenthal

  Hôpital de Nice

  PRINCIPAL INVESTIGATOR

• Eric Bellissant

  Centre de Méthodologie et de Gestion, CHU de Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: April 29, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: June 29, 2017

Record last verified: 2017-06

Locations

FR (1)