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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02125500
First Posted: April 29, 2014
Last Update Posted: June 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
  Purpose
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.

Condition Intervention Phase
Viral Hepatitis C HIV Drug: Sofosbuvir/Ledipasvir fixed dose Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Assess Efficacy and Safety of Sofosbuvir/Ledipasvir (GS-5885) Fixed-dose Combination in NS3/4A Protease Inhibitor-experienced Subjects With HCV Genotype 1 Infection and HIV Co-infection

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Sustained virologic response 12 weeks after discontinuation of therapy (SVR12), i.e. at week 36. [ Time Frame: 12 weeks post-treatment ]

Secondary Outcome Measures:
  • Adverse clinical and biological events that occur during the treatment and up to 24 weeks after the end of the treatment [ Time Frame: up to 24 weeks after the end of the treatment ]
  • Number and causes of poor adherence and treatment interruptions [ Time Frame: 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 [ Time Frame: Week 48 ]
  • Number of patients with HCV resistance mutations to Sofosbuvir and/or Ledipasvir [ Time Frame: from Day(D)0 to Week (W)24 ]
  • HCV viral load [ Time Frame: 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 ]
  • Plasma HIV RNA levels [ Time Frame: at Day 0, Week 4, 8, 12, 16, 20, 24, 36 and Week 48 ]
  • Assess drug-drug interactions between HCV et HIV drugs [ Time Frame: Day 0 and Week 4 ]
    Describe pharmacokinetic parameters of HIV drugs at Day 0 and Week 4 Describe pharmacokinetic parameters of Sofosbuvir and Ledipasvir at Week 4

  • Patient's reported outcomes evaluation [ Time Frame: Day 0, Week 12, Week 24 and Week 36 ]

Enrollment: 68
Study Start Date: August 2014
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sofosbuvir/Ledipasvir

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
SOF 400 mg/LDV 90 mg FDC tablet administered orally once daily
Other Names:
  • Sofosbuvir is also known as GS-7977 or PSI-7977.
  • Ledipasvir is also known as GS-5885.

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  • 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
  • Informed and signed consent for the main study and the Pharmacokinetic (PK ) sub-study (for the participating patients)
  • Patients with Health insurance

Non inclusion Criteria:

  • Child-Pugh B or C cirrhosis or history of decompensated cirrhosis.
  • Co-infection with Hepatitis B virus (HBV) (AgHBs +) with HBV DNA > 1000 UI/ml
  • Pregnant or breast-feeding women
  • Transplant recipients
  • Opportunistic infections (stage C), active or occurred within 6 months prior to baseline
  • Evolutive malignancy, including hepatocarcinoma which should be controlled prior to baseline
  • Alcohol or drug consumption which may affect the study participation according to the investigator. Patients included in a programme of substitution with methadone or buprenorphine could be enrolled. The opinion of a consultant in addictology is recommended for patients presenting with current drug use or drug use during the previous year.
  • Patients with a history of non-adherence, who will be at risk of being unable to respect the study follow-up timetable
  • Patients participating in another clinical trial within 30 days prior to inclusion
  • Hb < 10 g/dL (female) or < 11g/dL (male)
  • Platelets < 50 000/mm3
  • Neutrophil count < 750/mm3
  • Renal failure defined as creatinin clearance (MDRD) < 60ml/min
  • Other antiretroviral drugs than those allowed in the study
  • Contra-indications to Sofosbuvir, Ledipasvir
  • Contra-indicated treatment likely to interfere with the study drugs as listed in the protocol
  Contacts and Locations
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): NCT02125500


Locations
France
Centre de Méthodologie et de Gestion de Rennes
Rennes, France
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Eric Rosenthal Hôpital de Nice
Study Chair: Eric Bellissant Centre de Méthodologie et de Gestion, CHU de Rennes
  More Information

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT02125500     History of Changes
Other Study ID Numbers: ANRS HC31 SOFTRIH
First Submitted: April 24, 2014
First Posted: April 29, 2014
Last Update Posted: June 29, 2017
Last Verified: June 2017

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HCV/HIV coinfection
HCV genotype 1

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Coinfection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Infection
Parasitic Diseases
Sofosbuvir
Ledipasvir
Antiviral Agents
Anti-Infective Agents