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 is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
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)
ClinicalTrials.gov Identifier:
NCT02125500
First received: April 24, 2014
Last updated: July 30, 2014
Last verified: July 2014
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • SVR rate 24 weeks (i.e. W48) after the end of treatment and according to the HCV sub-type [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with HCV resistance mutations to Sofosbuvir and/or Ledipasvir [ Time Frame: from Day(D)0 to Week (W)24 ] [ Designated as safety issue: No ]
  • HCV viral load [ Time Frame: at D0, W1, W2, W4, W8, W12, W16, W20, W24, and 4, 8, 12, 18 and 24 weeks after the end of the treatment ] [ Designated as safety issue: No ]
  • Plasma HIV RNA levels [ Time Frame: at D0, W4, W8, W12, W16, W20, W24, W36 and W48 ] [ Designated as safety issue: No ]
  • Assess drug-drug interactions between HCV et HIV drugs [ Time Frame: D0 and W4 ] [ Designated as safety issue: No ]
    Describe pharmacokinetic parameters of HIV drugs at D0 and W4 Describe pharmacokinetic parameters of Sofosbuvir and Ledipasvir at W4

  • Patient's reported outcomes evaluation [ Time Frame: D0,W8, W24 and W48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2014
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 ≥ 15 kilopascal (kPa):
  • Previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4),

    • and/or significant liver biopsy (cumulative length ≥ 15mm and ≥ 6 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 25% of the mean value and a success rate of at least 80%).
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02125500

Contacts
Contact: Eric Rosenthal +33 ext 4 92 035851 rosenthal.e@chu-nice.fr
Contact: Claire Fougerou-Leurent +33 ext 299283753 Claire.FOUGEROU@chu-rennes.fr

Locations
France
Centre de Méthodologie et de Gestion de Rennes Not yet recruiting
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

No publications provided

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
Study First Received: April 24, 2014
Last Updated: July 30, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

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 A
Infection
Hepatitis C
Coinfection
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 22, 2014