A Prospective, Multicenter, Open, Randomized Phase 2a Trial to Confirm a Sustained Virological Suppression Defined as HIV-RNA <50 Copies/ml of 3 Different Doses of Fozivudine in Context to a Standard Zidovudine Based Antiretroviral Therapy Regimen After 24 Weeks of Treatment in ART naïve, Non Subtype B HIV-1 Infected Individuals From Tanzania and Ivory Coast
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Proportion of patients with plasma HIV RNA < 50 copies/ml
研究概览
简要总结
A prospective, multicenter, open, randomized Phase 2a trial to confirm a sustained virological suppression defined as HIV-RNA <50 copies/ml of 3 different doses of Fozivudine in context to a standard Zidovudine based antiretroviral therapy regimen after 24 weeks of treatment in ART naïve, non subtype B HIV-1 infected individuals from Tanzania and Ivory Coast.
详细描述
The study will evaluate four different oral 1st line antiretroviral regimens: three study arms will contain different doses of Fozivudine (FZD) plus Lamivudine (3TC) in a twice daily or once daily application plus once daily Efavirenz. The 4th study arm will contain standard Zidovudine (AZT)/Lamivudine (3TC) twice daily in a fixed dose combination plus once daily Efavirenz. The treatment duration will be 24 weeks.
In a pharmacokinetic Sub-Study Pharmacokinetic (PK) characteristics will be determined under controlled conditions in a sub population to evaluate PK values of the study drugs.
Primary Objective
The primary objective is to confirm a sustained virological suppression (HIV RNA <50 copies/ml) after 24 weeks of treatment between three different doses of Fozivudine (FZD) based antiretroviral 1st line treatment regimen in context to a standard Zidovudine (ZDV) based treatment regimen in non subtype B HIV-1 infected individuals from Africa.
Secondary Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Male or female ≥ 18 years of age.
- •Provide written or thump printed informed consent prior to all trial-related procedures
- •HIV-1 positive with an indication to start antiretroviral therapy (ART) according to WHO and/or country guidelines
- •ART naïve, including no history of antiretroviral medication during PMTCT or PEP
- •Patient agrees not to take any concomitant medication during the trial without informing the investigator. Traditional medicines should be specified with concomitant medications.
- •Availability throughout the study
- •Female patients of childbearing potential must have a negative pregnancy test and agree to use a highly effective method of birth control throughout participation in the trial and for 10 weeks after last dose (to cover duration of ovulation).
- •Agree to have home visits or active tracing if lost to follow up or any other event justifying a rapid visit of the patient at the clinical trial centre.
- •CD4 count ≥100 cells/μl
- •Hb ≥9.5 g/dl
- •Platelets ≥50,000 cells/mm3
- •Neutrophils ≥500 cells/ mm3
- •Bilirubin <2.5 x uln
- •ALT <2.5 x uln
- •Exclusion of Severe hepatic insufficiency (PT<50%)
- •Creatinine clearance calculated by Cockroft's formula ≥50 ml/min
- •Urine dipstick for protein and blood: negative or trace
排除标准
- •Deficiency in the patient, rendering it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
- •Presence of an uncontrolled, ongoing, opportunistic infection or of any severe or progressive disease including active TB or any other justified reason which in the opinion of the investigator could significantly inhibit study procedures. This includes any clinical signs possibly associated with any WHO stage 3 or 4, with still unconfirmed diagnosis such as fever, weight loss, diarrhoea or unexplained cough.
- •HIV-2 infection
- •Pregnancy or lactating mother
- •Unlikely to comply with protocol as judged by the principal investigator or his designate
- •Use of experimental therapeutic agents within 30 days of study entry.
- •Hepatitis B with positive HBsAg.
研究组 & 干预措施
FZD 600mg twice daily
FZD 3 tablets (600mg) twice daily / 3TC 1 tablet (150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: FZD (Drug)
FZD 600mg twice daily
FZD 3 tablets (600mg) twice daily / 3TC 1 tablet (150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: 3TC (Drug)
FZD 600mg twice daily
FZD 3 tablets (600mg) twice daily / 3TC 1 tablet (150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: EFV (Drug)
FZD 800mg once daily
FZD 4 tablets (800mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: FZD (Drug)
FZD 800mg once daily
FZD 4 tablets (800mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: 3TC (Drug)
FZD 800mg once daily
FZD 4 tablets (800mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: EFV (Drug)
FZD 1200mg once daily
FZD 6 tablets (1200mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: FZD (Drug)
FZD 1200mg once daily
FZD 6 tablets (1200mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: 3TC (Drug)
FZD 1200mg once daily
FZD 6 tablets (1200mg) once daily / 3TC 2 tablets (150mg) once daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: EFV (Drug)
AZT twice daily
1 tablet Combivir(AZT 300mg/3TC 150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: 3TC (Drug)
AZT twice daily
1 tablet Combivir(AZT 300mg/3TC 150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: EFV (Drug)
AZT twice daily
1 tablet Combivir(AZT 300mg/3TC 150mg) twice daily / EFV 1 capsule (600mg) once daily for the duration of 24 weeks
干预措施: AZT (Drug)
结局指标
主要结局
Proportion of patients with plasma HIV RNA < 50 copies/ml
时间窗: at week 24
次要结局
- Mean HIV log10 reduction compared to baseline(at week 2, 4 and 8)
- Incidence of resistance mutations after confirmed treatment failure (confirmed HIV RNA > 1000 copies/ml(at week 12 and week 24)
- Proportion of patients with plasma HIV RNA <50 copies/ml(at week 8 and 12)
- Proportion of patients with plasma HIV RNA < 400 copies/ml(at week 8, 12 and 24)
- Variation of circulating CD4+ lymphocyte count(up to week 24)
- Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) before and after the first dose(Day 1)
- Pharmacokinetic parameters (Cmax, AUC, CL/f, CLR, t1/2) at steady state(Week 4)
- Number of participants with Adverse Events as Measure of safety and tolerability(up to week 24)
- Variation of circulating total lymphocyte count(up to week 24)
- Proportion of clinical events stage 3 or 4 of WHO HIV classification(up to week 24)
研究者
Michael Hoelscher
Chief Investigator
Ludwig-Maximilians - University of Munich