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Clinical Trials

MainTitle

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)

This study is ongoing, but not recruiting participants.
Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)


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
NCT02405013

First received: February 20, 2015
Last updated: July 10, 2017
Last Verified: July 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
Hepatitis C
HIV Infection

Drug : Sofosbuvir
Drug : Ribavirin
Drug : Sofosbuvir
Drug : Ledipasvir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

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 Viral Load Response (SVR) [ Time Frame: Week 12 ]
Secondary Outcome Measures:
  • 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

Estimated Enrollment: 120
Study Start Date: October 2015
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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)
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)

Experimental: Sofosbuvir+Ledipasvir
Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (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®

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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

contacts and locations

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: NCT02405013

Locations

Cameroon
Clinique de la Cathédrale
Yaoundé, Cameroon
Côte D'Ivoire
Centre de suivi des donneurs de sang
Abidjan, Côte D'Ivoire
CHU de Youpougon - Service de Gastro-entéro-hépatologie
Abidjan, Côte D'Ivoire
Senegal
CHU Fann, Service des Maladies Infectieuses
Dakar, Senegal

Sponsors and Collaborators

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Investigators

Study Director: Raoul Moh, Dr Programme PACCI
Study Director: Babacar Sylla Institut de Médecine et d'Epidémiologie Appliquée
More Information

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: NCT02405013   History of Changes  
Other Study ID Numbers: ANRS 12311 TAC  
Study First Received: February 20, 2015  
Last Updated: July 10, 2017  

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

Africa
Hepatitis C
HIV
Antiviral treatment
Adults
HCV genotype 1
HCV genotype 2
HCV genotype 4

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
HIV Infections
Interferons
Ribavirin
Antiviral Agents
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.