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)

ANRS, Emerging Infectious Diseases

Status and phase: Completed; Phase 2

Conditions: Hepatitis C; HIV Infection

Treatments: Drug: Ribavirin; Drug: Sofosbuvir; Drug: Ledipasvir

Study type: Interventional

Funder types: Other

Identifiers

NCT02405013

ANRS 12311 TAC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Sofosbuvir+Ribavirin

Experimental group

Description:

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)

Treatment:

Drug: Sofosbuvir

Drug: Ribavirin

Drug: Sofosbuvir

Sofosbuvir+Ledipasvir

Experimental group

Description:

Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)

Treatment:

Drug: Sofosbuvir

Drug: Ledipasvir

Drug: Sofosbuvir