Back to results

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)

Primary Purpose

Hepatitis C, HIV Infection

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Sofosbuvir

Ribavirin

Sofosbuvir

Ledipasvir

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Africa, Hepatitis C, HIV, Antiviral treatment, Adults, HCV genotype 1, HCV genotype 2, HCV genotype 4

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Clinique de la Cathédrale
Centre de suivi des donneurs de sang
CHU de Youpougon - Service de Gastro-entéro-hépatologie
CHU Fann, Service des Maladies Infectieuses

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Sofosbuvir+Ribavirin

Sofosbuvir+Ledipasvir

Arm 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)

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

Outcomes

Primary Outcome Measures

Sustained Viral Load Response (SVR)

Secondary Outcome Measures

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

Viral kinetics as measured by SVR 24 and HCV-RNA

SVR 24 and HCV-RNA

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

Liver fibrosis

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

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

proportion of people reporting symptoms in the scale of symptoms experienced (scale of side effects perception SF12)

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).

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.

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

Biological events

Plasma HIV-RNA and CD4 count

Full Information

NCT ID

NCT02405013

First Posted

February 20, 2015

Last Updated

December 12, 2017

Sponsor

ANRS, Emerging Infectious Diseases

1. Study Identification

Unique Protocol Identification Number

NCT02405013

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

October 2015 (Actual)

Primary Completion Date

July 2017 (Actual)

Study Completion Date

November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ANRS, Emerging Infectious Diseases

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: To estimate the study treatment SVR24 rate To evaluate the clinical and biological tolerance of study treatment To describe HCV kinetics under HCV treatment, and identify associated factors To describe the evolution of HIV disease under HCV treatment in HVC-HIV co-infected patients 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 To identify factors associated with SVR12 and SVR24 (including HIV status) 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) Facilitate the detection and treatment of those infected with HCV by supporting national initiatives for access to strategies without interferon 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, HIV Infection

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sofosbuvir+Ribavirin

Arm Type

Experimental

Arm Description

Arm Title

Sofosbuvir+Ledipasvir

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir

Other Intervention Name(s)

Sovaldi®

Intervention Description

Sofosbuvir 400mg QD (Sovaldi®) in treatment-naïve patients infected with HCV genotype 2 (12-week course)

Intervention Type

Drug

Intervention Name(s)

Ribavirin

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir

Other Intervention Name(s)

Harvoni®

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ledipasvir

Other Intervention Name(s)

Harvoni®

Intervention Description

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

Primary Outcome Measure Information:

Title

Sustained Viral Load Response (SVR)

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

Tolerance

Description

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

Time Frame

36 weeks

Title

Viral kinetics as measured by SVR 24 and HCV-RNA

Description

SVR 24 and HCV-RNA

Time Frame

W0, W2, W4, W12, W24, W36

Title

HIV treatment clinical parameters

Description

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

Time Frame

36 weeks

Title

Liver fibrosis

Description

Elastometry score and only for cirrhotic patients : Child-Pugh score

Time Frame

W0, W24 and W36

Title

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

Description

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

Title

Quality of life

Description

proportion of people reporting symptoms in the scale of symptoms experienced (scale of side effects perception SF12)

Time Frame

36 weeks

Title

Performance of an unit of nanotechnology

Description

Time Frame

36 weeks

Title

Setting up the network:

Description

Time Frame

36 weeks

Title

Description

Time Frame

36 weeks

Title

Biological events

Description

Plasma HIV-RNA and CD4 count

Time Frame

W0, W24 and W36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raoul Moh, Dr

Organizational Affiliation

Programme PACCI

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Babacar Sylla

Organizational Affiliation

Institut de Médecine et d'Epidémiologie Appliquée

Official's Role

Study Director

Facility Information:

Facility Name

Clinique de la Cathédrale

City

Yaoundé

Country

Cameroon

Facility Name

Centre de suivi des donneurs de sang

City

Abidjan

Country

Côte D'Ivoire

Facility Name

CHU de Youpougon - Service de Gastro-entéro-hépatologie

City

Abidjan

Country

Côte D'Ivoire

Facility Name

CHU Fann, Service des Maladies Infectieuses

City

Dakar

Country

Senegal

12. IPD Sharing Statement

Learn more about this trial

We'll reach out to this number within 24 hrs