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

April 24, 2014
July 30, 2014
September 2014
November 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT02125500 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Viral Hepatitis C
  • HIV
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.
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.

Intervention: Drug: Sofosbuvir/Ledipasvir fixed dose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
70
November 2015
November 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
France
 
NCT02125500
ANRS HC31 SOFTRIH
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Not Provided
Principal Investigator: Eric Rosenthal Hôpital de Nice
Study Chair: Eric Bellissant Centre de Méthodologie et de Gestion, CHU de Rennes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP