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

NCT02405013 | Completed Phase 2 DMC

• 1 other identifier: ANRS 12311 TAC
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 4

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. 1.To estimate the study treatment SVR24 rate
2. 2.To evaluate the clinical and biological tolerance of study treatment
3. 3.To describe HCV kinetics under HCV treatment, and identify associated factors
4. 4.To describe the evolution of HIV disease under HCV treatment in HVC-HIV co-infected patients
5. 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. 6.To identify factors associated with SVR12 and SVR24 (including HIV status)
7. 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. 8.Facilitate the detection and treatment of those infected with HCV by supporting national initiatives for access to strategies without interferon
9. 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.

Conditions

Hepatitis C; HIV Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Sustained Viral Load Response (SVR)

  Week 12

Secondary Outcomes (10)

• Tolerance

  36 weeks

• Viral kinetics as measured by SVR 24 and HCV-RNA

  W0, W2, W4, W12, W24, W36

• HIV treatment clinical parameters

  36 weeks

• Liver fibrosis

  W0, W24 and W36

• 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

  W4, W8, W12

Study Arms (2)

Sofosbuvir+Ribavirin

EXPERIMENTAL

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; Drug: Ribavirin

Sofosbuvir+Ledipasvir

EXPERIMENTAL

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

Drug: Sofosbuvir; Drug: Ledipasvir

Interventions

Sofosbuvir DRUG

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

Also known as: Sovaldi®

Sofosbuvir+Ribavirin

Ribavirin DRUG

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+Ribavirin

Ledipasvir DRUG

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

Also known as: Harvoni®

Sofosbuvir+Ledipasvir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (4)

Clinique de la Cathédrale

Yaoundé, Cameroon

Location

Centre de suivi des donneurs de sang

Abidjan, Côte d’Ivoire

Location

CHU de Youpougon - Service de Gastro-entéro-hépatologie

Abidjan, Côte d’Ivoire

Location

CHU Fann, Service des Maladies Infectieuses

Dakar, Senegal

Location

Related Publications (1)

• Marcellin F, Mourad A, Lemoine M, Kouanfack C, Seydi M, Carrieri P, Attia A, Protopopescu C, Lacombe K, Boyer S. Patient-reported outcomes with direct-acting antiviral treatment for hepatitis C in West and Central Africa (TAC ANRS 12311 trial). JHEP Rep. 2022 Dec 28;5(3):100665. doi: 10.1016/j.jhepr.2022.100665. eCollection 2023 Mar.

  PMID: 36686592 DERIVED

MeSH Terms

Conditions

Hepatitis C; HIV Infections

Interventions

Sofosbuvir; Ribavirin; ledipasvir, sofosbuvir drug combination; ledipasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Raoul Moh, Dr

  Programme PACCI

  STUDY DIRECTOR

• Babacar Sylla

  Institut de Médecine et d'Epidémiologie Appliquée

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2015
• First Posted: April 1, 2015
• Study Start: October 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: November 1, 2017
• Last Updated: December 13, 2017

Record last verified: 2017-12

Locations

SE (1); CA (1); CÔ (2)