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Feasibility, Tolerance and Efficacy of Interferon-free, Antiviral Treatment With Sofosbuvir + Ribavirin for the Treatment of Genotype 2 and Sofosbuvir/Ledipasvir for the Treatment of Genotype 1 and 4 Hepatitis C Virus-infected Patients in West and Central Africa (TAC)

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ClinicalTrials.gov Identifier: NCT02405013
Recruitment Status : Completed
First Posted : April 1, 2015
Last Update Posted : December 13, 2017
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)

Tracking Information
First Submitted Date  ICMJE February 20, 2015
First Posted Date  ICMJE April 1, 2015
Last Update Posted Date December 13, 2017
Actual Study Start Date  ICMJE October 2015
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
Sustained Viral Load Response (SVR) [ Time Frame: Week 12 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2016)
  • Tolerance [ Time Frame: 36 weeks ]
    Grade 1, 2, 3 and 4 clinical or biological events (ACTG grading table), Adverse events-related HCV treatment discontinuation Adverse events-related ARV treatment modification
  • Viral kinetics as measured by SVR 24 and HCV-RNA [ Time Frame: W0, W2, W4, W12, W24, W36 ]
    SVR 24 and HCV-RNA
  • HIV treatment clinical parameters [ Time Frame: 36 weeks ]
    Number, nature and incidence of severe morbid events related to HIV, and clinical and biological events of grade 3 or 4 (ANRS scale) related to the ARV treatment
  • Liver fibrosis [ Time Frame: W0, W24 and W36 ]
    Elastometry score and only for cirrhotic patients : Child-Pugh score
  • Adherence measured by number of remaining tablets at each visit based on the number of tablets should have been taken as a percentage of the total dose [ Time Frame: W4, W8, W12 ]
    Number of remaining tablets at each visit based on the number of tablets should have been taken as a percentage of the total dose
  • Quality of life [ Time Frame: 36 weeks ]
    proportion of people reporting symptoms in the scale of symptoms experienced (scale of side effects perception SF12)
  • Performance of an unit of nanotechnology [ Time Frame: 36 weeks ]
    calculation of sensitivity / specificity / positive predictive value and negative of each of the steps that will be performed (genotype, viral load) compared to the reference measurement (PCR for viral load and sequencing to genotype).
  • Setting up the network: [ Time Frame: 36 weeks ]
    number of network meetings that have taken place before the end of the trial, the number of training sessions (on site or online) and the numbers enrolled in the network active partners. The ultimate goal is the establishment of an e-learning platform that will be an ancillary project.
  • Integration Access initiatives evaluated by the number of patients off protocol that will have access to new anti-HCV treatment due to "ACCESS" programs of pharmaceutical companies conducting such programs in Sub-Saharan Africa [ Time Frame: 36 weeks ]
    It will be evaluated by the number of patients off protocol that will have access to new anti-HCV treatment due to "ACCESS" programs of pharmaceutical companies conducting such programs in Sub-Saharan Africa
  • Biological events [ Time Frame: W0, W24 and W36 ]
    Plasma HIV-RNA and CD4 count
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Tolerance [ Time Frame: 36 and 48 weeks ]
    Grade 1, 2, 3 and 4 clinical or biological events (ACTG grading table), Adverse events-related HCV treatment discontinuation Adverse events-related ARV treatment modification
  • Viral kinetics as measured by SVR 24 and HCV-RNA [ Time Frame: W0, W2, W4, W12, W24, W36 and W48 following treatment initiation ]
    SVR 24 and HCV-RNA
  • HIV treatment clinical parameters [ Time Frame: 36 and 48 weeks ]
    Number, nature and incidence of severe morbid events related to HIV, and clinical and biological events of grade 3 or 4 (ANRS scale) related to the ARV treatment
  • Liver fibrosis [ Time Frame: W0, W24 and W48 ]
    Elastometry score and only for cirrhotic patients : Child-Pugh score
  • Adherence measured by number of remaining tablets at each visit based on the number of tablets should have been taken as a percentage of the total dose [ Time Frame: 36 and 48 weeks ]
    Number of remaining tablets at each visit based on the number of tablets should have been taken as a percentage of the total dose
  • Quality of life [ Time Frame: 36 and 48 weeks ]
    proportion of people reporting symptoms in the scale of symptoms experienced (scale of side effects perception SF12)
  • Performance of an unit of nanotechnology [ Time Frame: 36 and 48 weeks ]
    calculation of sensitivity / specificity / positive predictive value and negative of each of the steps that will be performed (genotype, viral load) compared to the reference measurement (PCR for viral load and sequencing to genotype).
  • Setting up the network: [ Time Frame: 36 and 48 weeks ]
    number of network meetings that have taken place before the end of the trial, the number of training sessions (on site or online) and the numbers enrolled in the network active partners. The ultimate goal is the establishment of an e-learning platform that will be an ancillary project.
  • Integration Access initiatives evaluated by the number of patients off protocol that will have access to new anti-HCV treatment due to "ACCESS" programs of pharmaceutical companies conducting such programs in Sub-Saharan Africa [ Time Frame: 36 and 48 weeks ]
    It will be evaluated by the number of patients off protocol that will have access to new anti-HCV treatment due to "ACCESS" programs of pharmaceutical companies conducting such programs in Sub-Saharan Africa
  • Biological events [ Time Frame: W0, W24 and W48 ]
    Plasma HIV-RNA and CD4 count
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Feasibility, Tolerance and Efficacy of Interferon-free, Antiviral Treatment With Sofosbuvir + Ribavirin for the Treatment of Genotype 2 and Sofosbuvir/Ledipasvir for the Treatment of Genotype 1 and 4 Hepatitis C Virus-infected Patients in West and Central Africa
Official Title  ICMJE TAC (Treatment Africa Hepatitis C) : Feasibility, Tolerance and Efficacy of Interferon-free, Antiviral Treatment With Sofosbuvir + Ribavirin for the Treatment of Genotype 2 and Sofosbuvir/Ledipasvir for the Treatment of Genotype 1 and 4 Hepatitis C Virus-infected Patients in West and Central Africa
Brief Summary

Primary Objective:

To evaluate the efficacy (sustained virological response 12 weeks after end-of-treatment [SVR12]) of 12-week course of an interferon-free regimen combining sofosbuvir and weight-dosed ribavirin (genotype 2), or sofosbuvir and ledipasvir (genotype 1 or 4) in treatment-naïve patients infected with HCV genotype 1, 2 or 4 in West and Central Africa

Secondary Objectives:

  1. To estimate the study treatment SVR24 rate
  2. To evaluate the clinical and biological tolerance of study treatment
  3. To describe HCV kinetics under HCV treatment, and identify associated factors
  4. To describe the evolution of HIV disease under HCV treatment in HVC-HIV co-infected patients
  5. To describe the changes of liver fibrosis based on non-invasive tests between treatment initiation, week 24, and week 36 after treatment, and estimate its association with SVR12 or SVR24
  6. To identify factors associated with SVR12 and SVR24 (including HIV status)
  7. To evaluate the performance of a nanodevice for rapid diagnosis of HCV viral load and genotypying and for assessing response to treatment (SVR12 and SVR24)
  8. Facilitate the detection and treatment of those infected with HCV by supporting national initiatives for access to strategies without interferon
  9. To set up a HCV clinical research network across French and English-speaking African countries, able to run large-scale comparative randomized clinical trials in a near future.
Detailed Description

Study design Multicenter, phase IIb, non randomized, open-label trial involving 3 groups of HCV-mono infected or HCV-HIV co-infected patients: group G1 (patients infected with HCV genotype 1), group G2 (patients infected with HCV genotype 2), and group G4 (patients infected with HCV genotype 4).

Number of Subjects A sample size of 40 patients per group will allow to demonstrate that the SVR12 is >70% ("expected efficacy" in difficult-to-treat patients, according to SPARE interim results), with the lower bound of the confidence interval being >50% ("unacceptable" efficacy). The overall sample size is 3x40=120 patients.

Participating Countries 3 countries from West Africa (Senegal, Côte d'Ivoire) and Central Africa (Cameroon) Number of Sites 5 clinical sites:

  • Côte d'Ivoire: Hepatology Departementat the Yopougon University Teaching Hospital, , Abidjan; and Blood Donors clinic (CMSDS) at the National Blood Bank (CNTS), Abidjan
  • Senegal: CRCF (Centre Régional de Recherche et de Formation), and Fann University Teaching Hospital
  • Cameroon: Clinique de la Cathédrale

Duration of Recruitment : 6 months

Duration of Treatment : 12 weeks

Duration of follow-up : 36 weeks

Anticipated Start Date / Anticipated End Date: November 2015 - October 2016

Target Population /Demographics : Patients >18 years, living with chronic hepatitis C genotype 1, 2 or 4, in West and Central Africa. In each genotype group approx. 50% of patients will be HCV-HIV co-infected, and 50% of patients will be mono-infected with HCV

This study will enable us to assess the feasibility, tolerance and efficacy of such a strategy in resource-constrained settings with considerable treatment needs.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis C
  • HIV Infection
Intervention  ICMJE
  • Drug: Sofosbuvir
    Sofosbuvir 400mg QD (Sovaldi®) in treatment-naïve patients infected with HCV genotype 2 (12-week course)
    Other Name: Sovaldi®
  • Drug: Ribavirin
    Ribavirin weight-adjusted dosing (1000mg BID in patients < 75kg and 1200mg BID in patients ≥ 75kg) in treatment-naïve patients infected with HCV genotype 2 (12-week course)
  • Drug: Sofosbuvir
    Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
    Other Name: Harvoni®
  • Drug: Ledipasvir
    Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
    Other Name: Harvoni®
Study Arms  ICMJE
  • Experimental: Sofosbuvir+Ribavirin
    Sofosbuvir 400mg QD (Sovaldi®) + Ribavirin weight-adjusted dosing (1000mg BID in patients < 75kg and 1200mg BID in patients ≥ 75kg) in treatment-naïve patients infected with HCV genotype 2 (12-week course)
    Interventions:
    • Drug: Sofosbuvir
    • Drug: Ribavirin
  • Experimental: Sofosbuvir+Ledipasvir
    Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
    Interventions:
    • Drug: Sofosbuvir
    • Drug: Ledipasvir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2017
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age≥18 years
  • Confirmed G1, G2 or G4 HCV infection
  • Plasma HCV-RNA ≥1000 IU/mL
  • No history of HCV treatment of any kind
  • Willingness to use a birth control method (hormonal or intrauterine device for women, condoms for men), starting before HCV treatment initiation and continued until 4months (women) and 7 months (men) after end of treatment.
  • Weight ≥40 kg and ≤125 kg

For patients infected with HIV :

  • Confirmed HIV-1 infection
  • Stable HIV treatment for at least 8 weeks with two NRTIs (tenofovir or abacavir, and lamivudine or emtricitabine) and a third agent (raltegravir, lopinavir/ritonavir, atazanavir/ritonavir, darunavir/ritonavir, efavirenz, nevirapine)
  • Current CD4+ lymphocytes count ≥100/mm3
  • Current plasma HIV-1 RNA <200 copies/mL

Exclusion Criteria:

For each patient:

  • Cirrhosis classified Child-Pugh B or C
  • Co-infection by the Hepatitis B virus
  • Pregnant or breastfeeding ongoing
  • History of transplantation of organs or tissues
  • Progressive Cancer, including hepatocellular carcinoma
  • Epilepsy
  • Sickle Cell Disease
  • A history of myocardial infarction or other severe heart disease
  • Excessive consumption of alcohol or drug users, in the absence of substitution by methadone, a stable weaning for more than three months should be required
  • Ongoing Participation in another clinical trial
  • Contraindications to the Sofosbuvir as defined in the Summary of Product Characteristics
  • At least one of the following laboratory abnormalities:

Haemoglobin <10 g / 100 ml (woman) <11 g / 100 ml (man) Platelet count <50,000 / mm3 polymorphonuclear neutrophils rate <750 / mm3 Creatinine clearance <50ml / min

For patients infected with HIV:

  • Severe opportunistic infections in the last 6 months
  • Poor adherence to antiretroviral treatment history
  • Use of antiretroviral drugs other than those permitted in the test
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Côte D'Ivoire,   Cameroon,   Senegal
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02405013
Other Study ID Numbers  ICMJE ANRS 12311 TAC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Study Sponsor  ICMJE French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Raoul Moh, Dr Programme PACCI
Study Director: Babacar Sylla Institut de Médecine et d'Epidémiologie Appliquée
PRS Account French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Verification Date December 2017

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