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

Hepatitis C Clinical Trial

— TAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02405013
• Other study ID #: ANRS 12311 TAC
• Status: Completed
• Phase: Phase 2
• First received: February 20, 2015
• Last updated: December 12, 2017
• Start date: October 2015
• Est. completion date: November 2017

Study information

• Verified date: December 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: November 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• HIV Infection
• HIV Infections

Intervention

Drug:
• Sofosbuvir
Sofosbuvir 400mg QD (Sovaldi®) in treatment-naïve patients infected with HCV genotype 2 (12-week course)
• 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)
• Sofosbuvir
Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
• Ledipasvir
Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)

Locations

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

Sponsors (1)

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

Countries where clinical trial is conducted

Cameroon,  Côte D'Ivoire,  Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Viral Load Response (SVR)		Week 12
Secondary	Tolerance	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	36 weeks
Secondary	Viral kinetics as measured by SVR 24 and HCV-RNA	SVR 24 and HCV-RNA	W0, W2, W4, W12, W24, W36
Secondary	HIV treatment clinical parameters	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	36 weeks
Secondary	Liver fibrosis	Elastometry score and only for cirrhotic patients : Child-Pugh score	W0, W24 and W36
Secondary	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	Number of remaining tablets at each visit based on the number of tablets should have been taken as a percentage of the total dose	W4, W8, W12
Secondary	Quality of life	proportion of people reporting symptoms in the scale of symptoms experienced (scale of side effects perception SF12)	36 weeks
Secondary	Performance of an unit of nanotechnology	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).	36 weeks
Secondary	Setting up the network:	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.	36 weeks
Secondary	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	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	36 weeks
Secondary	Biological events	Plasma HIV-RNA and CD4 count	W0, W24 and W36