Medical Research Council Clinical Trials Unit at University College London, UK.
Medical Research Council Clinical Trials Unit at University College London, UK.
Contemp Clin Trials. 2024 Jul;142:107540. doi: 10.1016/j.cct.2024.107540. Epub 2024 Apr 16.
There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing.
D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm.
D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial.
International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57.
gov: NCT04337450.
人们越来越感兴趣地将两种药物联合用于 HIV 治疗，以降低毒性并提高可接受性。D3 试验评估了 DTG/3TC 在儿童和青少年中的疗效和安全性，并包括一项用于儿童药物许可的嵌套药代动力学（PK）子研究。
D3 是一项正在进行的、开放性、III 期、96 周非劣效性随机对照试验（RCT），在南非、西班牙、泰国、乌干达和英国进行。D3 招募了 386 名年龄在 2-<15 岁、病毒学抑制≥6 个月、无既往治疗失败的儿童。参与者按照地区、年龄（2-<6、6-<12、12-<15 岁）和入组时 DTG 的使用情况（允许参与者在入组时开始使用 DTG）进行 1:1 随机分组，接受 DTG/3TC 或 DTG 加两种核苷逆转录酶抑制剂（NRTIs）治疗。主要结局是 96 周时确认 HIV-1 RNA 病毒反弹≥50 拷贝/mL。该试验采用 Smooth Away From Expected（SAFE）非劣效性边界，该边界根据对照臂中的观察到的事件风险指定非劣效性边界和显著性水平。嵌套 PK 子研究评估了 DTG/3TC 臂中的 WHO 体重带调整剂量。
D3 是第一项评估 DTG/3TC 在儿童和青少年中的比较试验。考虑到整合 PK 子研究和提供数据以快速进行监管提交的意义，仔细考虑了确保正在进行的试验完整性的问题。该试验在主要分析中使用了创新性的非劣效性边界，以允许对照臂中的确认病毒反弹风险低于预期，同时确保结果的可解释性并保持在已资助试验中的计划样本量。
国际标准随机对照临床试验编号注册：ISRCTN82656678。欧洲临床试验数据库：2020-001426-57。
gov：NCT04337450。
