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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Sustained Viral Load Response (SVR)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Sofosbuvir+Ribavirin
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)
干预措施: Sofosbuvir (Drug)
Sofosbuvir+Ribavirin
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)
干预措施: Ribavirin (Drug)
Sofosbuvir+Ledipasvir
Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
干预措施: Sofosbuvir (Drug)
Sofosbuvir+Ledipasvir
Sofosbuvir/Ledipasvir 400mg/90mg (Harvoni®) in treatment-naïve patients infected with HCV genotype 1 or genotype 4 (12-week course)
干预措施: Ledipasvir (Drug)
结局指标
主要结局
Sustained Viral Load Response (SVR)
时间窗: Week 12
次要结局
- Liver fibrosis(W0, W24 and W36)
- Setting up the network:(36 weeks)
- Quality of life(36 weeks)
- HIV treatment clinical parameters(36 weeks)
- 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)
- Performance of an unit of nanotechnology(36 weeks)
- Biological events(W0, W24 and W36)
- 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(36 weeks)
- Tolerance(36 weeks)
- Viral kinetics as measured by SVR 24 and HCV-RNA(W0, W2, W4, W12, W24, W36)