A Phase I/II, Open-Label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Rilpivirine in Antiretroviral Naive HIV-1 Infected Children, < 12 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Toxicity endpoint: termination from treatment due to a suspected adverse drug reaction (SADR)
研究概览
简要总结
Development of tolerable and effective antiretroviral (ARV) drugs for use in children and adolescents remains a high priority. First-line therapy with non-nucleoside reverse transcriptase inhibitors (NNRTIs) has proven to be effective for HIV-1-infected infants, children, and adolescents. This study will evaluate the safety, effectiveness, and dosing levels of the NNRTI rilpivirine (RPV) when given with two other ARV drugs in treatment-naive, HIV-1-infected children less than 12 years of age.
详细描述
This study will enroll HIV-1-infected children less than 12 years of age who are naive to antiretroviral therapy (ART) (have never taken ARV drugs). Study participants will be assigned to 1 of 2 cohorts based on age. Cohort 1 will include children at least 6 years of age to less than 12 years of age. Cohort 2 will include children at least 2 years of age to less than 6 years of age. Each cohort will consist of two stages: Stage 1 and Stage 2. Stage 1 will be the initial dose finding stage. Participants will begin treatment with daily RPV and 2 nucleoside reverse transcriptase inhibitors (NRTIs). The 2 NRTIs will be selected by the site investigator but will not be provided through the study. This stage of the study will involve intense pharmacokinetic (PK) sampling to evaluate the safety, tolerability, and antiviral activity of RPV, which will allow for the selection of an RPV dose to use in Stage 2 of the study. Participants in both cohorts will remain on RPV-based therapy for up to 48 weeks.
Study enrollment will begin with Cohort 1. Once data from Cohort 1 has been reviewed and an RPV dose has been approved, enrollment for Cohort 2 will begin.
Study participation will include at least 12 study visits over 48 weeks. Participants who complete 48 weeks of RPV treatment and are benefiting from the drug will continue on the study and receive RPV as part of a long-term safety follow-up for a minimum of 4 additional years. Study visits in this stage of the study will occur every 24 weeks.
At most visits, participants will give a medical history and undergo a physical exam, blood collection, and urine collection. At some visits, participants will also undergo an electrocardiogram (ECG), adrenocorticotropic hormone (ACTH) stimulation test (consisting of blood collection and an injection of ACTH), and determination of the participant's stage of sexual development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: 6 to less than 12 years of age
Participants in this arm will be at least 6 but younger than 12 years of age; they will receive the study drug RPV together with 2 other NRTIs.
干预措施: Rilpivirine (Drug)
Cohort 2: 2 to less than 6 years of age
Participants in this arm will be at least 2 but younger than 6 years of age; they will receive the study drug RPV together with 2 other NRTIs.
干预措施: Rilpivirine (Drug)
结局指标
主要结局
Toxicity endpoint: termination from treatment due to a suspected adverse drug reaction (SADR)
时间窗: Measured through Week 24
Failure to meet PK guidelines
时间窗: Measured through Week 48
Main PK parameters include the area under the plasma concentration-time curve over 24 hours (AUC24h) and the maximum observed plasma concentration (Cmax)
Toxicity endpoint: death
时间窗: Measured through Week 24
Toxicity endpoint: adverse events (AEs) or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medication
时间窗: Measured through Week 24
次要结局
- AEs or laboratory toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medications(Measured through Week 48)
- Adverse events meeting the International Conference on Harmonisation (ICH) seriousness criteria(Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240))
- Treatment discontinued due to toxicity or virologic failure(Measured through participant's last study visit (through Week 48 or, for participants in long-term safety follow-up, through Week 240))
- Failure to suppress plasma HIV RNA to less than 400 copies/mL (confirmed within 2 to 4 weeks)(Measured at Week 24 and Week 48)
- Virologic outcome as per Snapshot and time to loss of virologic response (TLOVR)(Measured at Week 24 and Week 48)
- Failure to achieve undetectable plasma HIV RNA (less than 40 copies/mL on Abbott RealTime HIV-1 assay, confirmed within 2 to 4 weeks)(Measured at Week 24 and Week 48)
- Sustained decline in absolute CD4 percent of greater than 5% any time after 12 weeks of therapy(Measured through Week 48)
- Long-term safety (AEs, toxicities of Grade 3 or higher severity, or deaths at least possibly related to treatment) after 48 weeks(Measured through Week 48)