CHAPAS-5: An Adaptive Platform Trial for Evaluation of Novel Treatment Regimens in Children and Adolescents With HIV in Africa
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 800
- 主要终点
- The proportion of participants alive with HIV VL <400 c/mL at 48 weeks
研究概览
简要总结
The goal of the CHAPAS-5 clinical trial is to find out how well different HIV treatments work in children and young people (from 4 weeks up to under 15 years old) living with HIV, including those starting treatment for the first time and those whose current treatment is not working well.
The study aims to learn whether newer or different combinations of medicines can better control the virus, be safer, and be easier to take.
The main questions it aims to answer are:
- Can these treatments help children stay alive and keep their HIV virus at very low levels (viral load below 400) after 48 weeks?
- Which treatment options are most effective, safest, and easiest for children and their carers to use?
Researchers will compare different treatment groups to see if some medicines work better than others. Participants will be given one of several HIV treatment combinations (all already used in care), and these will be compared to see if they lead to:
- Better control of HIV
- Fewer side effects
- Improved quality of life
Participants will:
- Be randomly assigned (like flipping a coin by computer) to one suitable HIV treatment
- Take their HIV medication every day as prescribed
- Attend clinic visits over about 1-2 years
At these visits, they will:
-
Have blood tests to check HIV levels and general health
-
Have health check-ups (e.g. weight, symptoms, side effects)
-
Answer simple questionnaires about:
-
How easy the treatment is to take
-
Mood, sleep, and wellbeing
-
Quality of life
-
Receive support to help them take their medication regularly
Some participants may also take part in optional extra studies (for example, to understand how the drugs work in the body).
Overall, this study aims to identify the best HIV treatments for children and young people, so future care can be more effective, safer, and easier to follow.
详细描述
CHAPAS-5 is a study organised by an international group of researchers from the United Kingdom, Uganda, Mozambique, Zimbabwe, Italy and the Netherlands.
Background HIV is a virus that attacks the cells that help the body fight infection. This means that a person living with HIV may be more likely to become ill as they are not able to fight off other infections and cope with other illnesses. HIV is usually treated by taking three or four different medicines. Some of these medicines can be combined into one tablet. Depending on the medicines used, tablets may need to be taken either once or twice every day. The medicine is called antiretroviral therapy (ART).
The goal of HIV treatment is to make sure the HIV virus in the blood remains very low; this is called virological suppression. If this goal is achieved and sustained life-long, then people with HIV infection can live a healthy life, with a normal life expectancy. Adults living with HIV have many treatment options. This means that they can change treatments more easily if they get side-effects or if a treatment stops working.
Children and adolescents living with HIV have fewer available treatments than adults and only limited alternatives if they develop side-effects or if their current treatment stops working. As HIV treatment needs to be life-long for a person to live a long, healthy and productive life, it is really important that better treatment options are made available to children and adolescents.
A clinical trial is a study that compares different treatments to find out which works best. Traditional trials usually compare only two treatments at a time. CHAPAS-5 uses a newer trial design that can compare several treatments at the same time in two different groups of children. It will test three treatment options for children and adolescents starting ART for the first time (ART-naïve), and four options for those already on ART whose current treatment is not working well (ART-experienced).
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
- 4 Weeks 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 4 weeks to <15 years* with confirmed HIV infection
- •Weight ≥3kg and <30kg*
- •Written informed consent obtained (and assent if applicable)
- •Willing to adhere to a minimum of 48 weeks' follow-up
- •Upper limits of 15 years and 30kg are for initial treatment options and may be amended when further treatment options are introduced (through a protocol amendment)
- •Planning to start first-line ART
- •Virologically unsuppressed with VL ≥400 c/mL at screening
- •ART-EXPERIENCED
- •ART-experienced, and on DTG-based ART, and have been on DTG-based ART for at least 6-months prior to screening
- •Virologically unsuppressed for at least 3 months, demonstrated by two consecutive VLs ≥400 c/mL in the last year; the second VL must be at screening
- •Received adherence counselling as per standard practice prior to screening
排除标准
- •Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR both ALT ≥3xULN and bilirubin ≥2xULN at screening**
- •Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Severe renal impairment, defined as creatinine clearance <30 mL/min/1.73m2, at screening**
- •Severe life-threatening illness (not expected to survive beyond two weeks) as determined by the investigator's clinical judgment.
- •Eligible for less than two permitted treatment options based on tables 3 (ART-naive participants) and 4 (ART-experienced participants)
- •Concurrent participation in another clinical trial of an investigational medicinal product (IMP), medical device or other intervention.
- •If ALT, bilirubin or creatinine results are available before randomisation and meet exclusion criteria, the child should not be randomised. However, randomisation may proceed while awaiting these results. If results become available after randomisation and meet exclusion criteria, the participant must be recalled and withdrawn from the trial and the InCTU trial physician contacted to discuss clinical management.
研究组 & 干预措施
ART Naïve DTG/TAF/FTC
ART Naïve participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Dolutegravir (DTG) (Drug)
ART Experienced DTG/ABC/3TC
ART Experienced participants receiving dolutegravir, abacavir, lamivudine
干预措施: Abacavir (ABC) (Drug)
ART Experienced DRV/r /ABC/3TC
ART Experienced participants receiving darunavir, ritonavir, abacavir, lamivudine
干预措施: Lamivudine (3TC) (Drug)
ART Experienced DRV/r /ABC/3TC
ART Experienced participants receiving darunavir, ritonavir, abacavir, lamivudine
干预措施: Darunavir (DRV) (Drug)
ART Experienced DRV/r /ABC/3TC
ART Experienced participants receiving darunavir, ritonavir, abacavir, lamivudine
干预措施: Ritonavir (RTV) (Drug)
ART Naïve DTG/ABC/3TC
ART Naïve participants receiving dolutegravir, abacavir, lamivudine
干预措施: Lamivudine (3TC) (Drug)
ART Experienced DTG/ABC/3TC
ART Experienced participants receiving dolutegravir, abacavir, lamivudine
干预措施: Dolutegravir (DTG) (Drug)
ART Experienced DRV/r /ABC/3TC
ART Experienced participants receiving darunavir, ritonavir, abacavir, lamivudine
干预措施: Abacavir (ABC) (Drug)
ART Experienced DRV/r /TAF/FTC
ART Experienced participants receiving darunavir, ritonavir, tenofovir alafenamide, emtricitabine
干预措施: Ritonavir (RTV) (Drug)
ART Naïve DTG/ABC/3TC
ART Naïve participants receiving dolutegravir, abacavir, lamivudine
干预措施: Dolutegravir (DTG) (Drug)
ART Naïve DTG/3TC
ART Naïve participants receiving dolutegravir, lamivudine
干预措施: Dolutegravir (DTG) (Drug)
ART Experienced DTG/TAF/FTC
ART Experienced participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Tenofovir alafenamide (TAF) (Drug)
ART Experienced DRV/r /TAF/FTC
ART Experienced participants receiving darunavir, ritonavir, tenofovir alafenamide, emtricitabine
干预措施: Tenofovir alafenamide (TAF) (Drug)
ART Naïve DTG/TAF/FTC
ART Naïve participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Emtricitabine (FTC) (Drug)
ART Experienced DTG/ABC/3TC
ART Experienced participants receiving dolutegravir, abacavir, lamivudine
干预措施: Lamivudine (3TC) (Drug)
ART Naïve DTG/ABC/3TC
ART Naïve participants receiving dolutegravir, abacavir, lamivudine
干预措施: Abacavir (ABC) (Drug)
ART Naïve DTG/3TC
ART Naïve participants receiving dolutegravir, lamivudine
干预措施: Lamivudine (3TC) (Drug)
ART Experienced DTG/TAF/FTC
ART Experienced participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Emtricitabine (FTC) (Drug)
ART Naïve DTG/TAF/FTC
ART Naïve participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Tenofovir alafenamide (TAF) (Drug)
ART Experienced DTG/TAF/FTC
ART Experienced participants receiving dolutegravir, tenofovir alafenamide, emtricitabine
干预措施: Dolutegravir (DTG) (Drug)
ART Experienced DRV/r /TAF/FTC
ART Experienced participants receiving darunavir, ritonavir, tenofovir alafenamide, emtricitabine
干预措施: Emtricitabine (FTC) (Drug)
ART Experienced DRV/r /TAF/FTC
ART Experienced participants receiving darunavir, ritonavir, tenofovir alafenamide, emtricitabine
干预措施: Darunavir (DRV) (Drug)
结局指标
主要结局
The proportion of participants alive with HIV VL <400 c/mL at 48 weeks
时间窗: Week 48
For participants with an initial week 48 VL ≥400 copies/mL, a repeat VL is required, and the repeat value will be used for outcome classification.
次要结局
- The proportion of participants with emergent drug resistance by 48 weeks(Week 48)
- Time to first serious adverse events (SAEs), grade ≥3 adverse events (AEs) and ART-modifying events of any grade(From randomisation to the last study visit (minimum of 48 weeks))
- Time to first new or recurrent WHO 3/4 events, or death(From randomisation to the last study visit (minimum of 48 weeks))
- Change in CD4 count and CD4 percentage from baseline to week 48(From baseline to week 48)
- Change in weight and BMI-for-age from baseline to week 48(From baseline to week 48)
- The proportion of participants alive with HIV VL<1000 c/mL at 48 weeks(Week 48)
- The proportion of participants with cross-sectional HIV VL ≥50 copies/mL, ≥400 copies/mL, and ≥1000 copies/mL at 48 weeks(Week 48)