Clinical trial NCT02405013: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
HIV Infection
Keywords: Africa
Hepatitis C
HIV
Antiviral treatment
Adults
HCV genotype 1
HCV genotype 2
HCV genotype 4
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2015-04-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Sustained Viral Load Response (SVR)
timeFrame: Week 12
Secondary outcomes:
measure: Tolerance
timeFrame: 36 weeks
measure: Viral kinetics as measured by SVR 24 and HCV-RNA
timeFrame: W0, W2, W4, W12, W24, W36
measure: HIV treatment clinical parameters
timeFrame: 36 weeks
measure: Liver fibrosis
timeFrame: W0, W24 and W36
measure: 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
timeFrame: W4, W8, W12
measure: Quality of life
timeFrame: 36 weeks
measure: Performance of an unit of nanotechnology
timeFrame: 36 weeks
measure: Setting up the network:
timeFrame: 36 weeks
measure: 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
timeFrame: 36 weeks
measure: Biological events
timeFrame: W0, W24 and W36
Other outcomes:
Locations:
city: Yaoundé
country: Cameroon
facility: Clinique de la Cathédrale
city: Abidjan
country: Côte D'Ivoire
facility: Centre de suivi des donneurs de sang
city: Abidjan
country: Côte D'Ivoire
facility: CHU de Youpougon - Service de Gastro-entéro-hépatologie
city: Dakar
country: Senegal
facility: CHU Fann, Service des Maladies Infectieuses
Study officials:
affiliation: Programme PACCI
name: Raoul Moh, Dr
role: STUDY_DIRECTOR
affiliation: Institut de Médecine et d'Epidémiologie Appliquée
name: Babacar Sylla
role: STUDY_DIRECTOR
References: