NCT06203132招募中3 期
Phase III, Open-label, Randomized, Multicenter Trial EvaLuating the Non-inferiority of DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 610
- 试验地点
- 23
- 主要终点
- Non-inferiority of doravirine in combination with tenofovir and lamivudine as compared to dolutegravir in combination with tenofovir and lamivudine or emtricitabine in terms of virological efficacy at week 48
研究概览
简要总结
Phase III trial evaluating doravirine as an alternative to dolutegravir in treatment naïve people living with HIV-1 infection.
详细描述
Phase III, multicenter, open-label, randomized, non-inferiority clinical trial which aims to assess the non-inferiority of doravirine in association with tenofovir and lamivudine, as compared to dolutegravir in association with tenofovir and lamivudine or emtricitabine.
This trial will be implemented in Brazil, Cameroon, Côte d'Ivoire, France, Mozambique and Thailand.
Six hundred and ten patients will be enrolled and followed for 96 weeks after entry in the trial (=ART initiation).
Primary endpoint will assess virological efficacy at Week 48, measured by the proportion of subjects achieving HIV-1 RNA <50 copies/mL, in HIV-1 infected, treatment-naive subjects with pre-treatment viral load (HIV-1 RNA) ≥ 1,000 copies/mL.
Secondary endpoints are planned at W48 and W96.
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
- •Be at least 18 years of age on the day of signing the informed consent.
- •Be HIV-1 positive as determined according to national testing strategies
- •Have a plasma HIV-1 RNA ≥1000 copies/mL within 30 days prior to the randomization,
- •Have HIV treatment indication based on physician assessment according to local treatment guidelines
- •Be naïve to antiretroviral therapy (ART) including investigational antiretroviral agents
- •For women or transgender men of childbearing potential i.e. of childbearing age who are not menopausal, or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or not refraining from sexual activity: negative urinary test for pregnancy and acceptance to use contraceptive methods
- •Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial.
- •Non-inclusion Criteria:
- •Has ongoing (pulmonary or extra-pulmonary) tuberculosis
- •Has any other history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
- •Is infected with HIV-2 or co-infected with HIV-1 and HIV-2
- •Has received cabotegravir long acting or dapivirine pre-exposure prophylaxis (PrEP).
- •Has received oral pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) in the past three months or has had no negative HIV-1 serology performed
- •Has documented or known resistance or possible resistance to study drugs (in France and where national guidelines recommend screening for primary resistance before starting first-line ART) as defined by the ANRS MIE AC43 Resistance group
- •Has the following laboratory values at screening visit, within 30 days prior to the randomization:
- •AST (SGOT) and ALT (SGPT) >4.0 x upper limit of normal
- •Estimated glomerular filtration rate at time of screening <60 mL/min/1.73m², based on the CKD-EPI equation
- •Has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
- •Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
- •Requires or is anticipated to require any of the prohibited or contraindicated medications noted in the trial protocol.
- •Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
- •Is pregnant, breastfeeding, or expecting to conceive at any time during the study.
- •Has any condition which might, in the investigator's opinion, compromise the safety of treatment and/or patient's adherence to study procedure.
- •Is a person under guardianship or deprived of freedom by a judicial or administrative decision
排除标准
- 未提供
研究组 & 干预措施
Doravirine arm
Experimental
Doravirine (100 mg) + tenofovir DF (300 mg) + lamivudine (300mg) administered daily
干预措施: Doravirine + tenofovir DF + lamivudine (Drug)
Dolutegravir arm
Active Comparator
Dolutegravir (50 mg) + tenofovir DF 300 mg + XTC (300 mg if lamivudine or 200 mg if emtricitabine) administered daily
干预措施: Dolutegravir + tenofovir DF + lamivudine or emtricitabine (Drug)
结局指标
主要结局
Non-inferiority of doravirine in combination with tenofovir and lamivudine as compared to dolutegravir in combination with tenofovir and lamivudine or emtricitabine in terms of virological efficacy at week 48
时间窗: Week 48
The non-inferiority will be assessed in terms of virologic efficacy at week 48 under allocated treatment using the FDA snapshot algorithm (window period of 42-54 weeks), and measured by the proportion of subjects achieving a rate of HIV 1 RNA \<50 copies/mL, in HIV-1 infected, treatment-naive subjects with pre-treatment viral load (HIV-1 RNA) ≥ 1,000 copies/mL. The rate of HIV 1 RNA will be measured by RT-PCR.
次要结局
- Occurrence of obesity(Week 48; Week 96)
- Occurrence of insulin resistance(Week 48; Week 96)
- Occurrence of hypertension(Week 48; Week 96)
- Non-inferiority of DOR in association with TDF and 3TC, compared to DTG in association with TDF and 3TC or FTC, in terms of virologic efficacy(Week 96)
- Occurrence of virological failures(Virological failure)
- Occurrence of HIV-1 drug resistances in patients with confirmed virological failure(Virological Failure)
- Virological efficacy at a threshold of HIV 1 RNA<200 copies/mL(Week 48; Week 96)
- Virological efficacy at a threshold of HIV 1 RNA<1000 copies/mL(Week 48; Week 96)
- Effect of baseline RT and integrase mutations on virological response(Week 48; Week 96)
- Occurrence of combined overweight and obesity(Week 48; Week 96)
- Occurrence of weight gain ≥10% absolute body weight(Week 48; Week 96)
- Changes in absolute weight gain(Week 48; Week 96)
- Occurrence of diabetes(Week 48; Week 96)
- Safety and tolerability(Week 48; Week 96)
- Changes in waist circumference, hip circumference and waist-to-hip ratio(Week 48; Week 96)
- Changes in fasting glycemia and insulin(Week 48; Week 96)
- Changes in fasting serum lipids(Week 48; Week 96)
- Changes in estimated glomerular filtration rate(Week 48; Week 96)
- Occurrence of cardiovascular abnormalities(Week 48; Week 96)
- Changes in liver steatosis and clinically significant fibrosis(Week 48; Week 96)
- Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH)(Week 48; Week 96)
- Changes in liver diseases biomarkers(Week 48; Week 96)
- Changes in mental health and quality of life outcomes(Week 24; Week 48; Week 96)
- Occurrence of Acquired Immune Deficiency Syndrome (AIDS), tuberculosis, Immune Reconstitution Inflammatory Syndrome (IRIS) or death(Week 48; Week 96)
- Description of antiretroviral drugs trough plasma concentration in each arm(Week 4; Week 24; Week 48; Week 96)
- Assessment of the effect of antiretroviral drugs trough plasma concentration on virological response(Week 4; Week 24; Week 48; Week 96)
- Determining DOR, DTG and M9 trough plasma concentration thresholds predictive of virological response(Week 4; Week 24; Week 48; Week 96)
- Assessment of the effect of antiretroviral drugs trough plasma concentration on safety endpoints(Week 4; Week 24; Week 48; Week 96)
- Changes in CD4 cell count, CD4 percentage, CD8 cell count, CD8 percentage, CD4/CD8 ratio(Week 48; Week 96)
- Description of the distribution of CYP3A5/4 mutations according to ARV regimen(Study long)
- Adherence to ART(Week 48; Week 96)
- Assessment of the impact of CYP3A5/4 mutations on PK(Study long)
- Assessment of the impact of CYP3A5/4 mutations on virological response and side effects(Study long)
- Explore additional polymorphism (i.e. UGT1A1) according to literature update(Baseline)
- Changes in truncal fat distribution in a sub-group of cisgender women enrolled in the trial(Week 48; Week 96)
- Cost-effectiveness and budget impact of using DOR-based versus DTG-based antiretroviral regimens(Study long)
- Changes in adipose tissue markers and immune activation markers in a sub-group of cisgender women enrolled in the trial(Week 48; Week 96)
- Changes in fat quality in a sub-group of cisgender women enrolled in the trial(Week 48)
研究者
研究点 (23)
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