Centre for the Aids Programme of Research in South Africa, Durban, South Africa
Centre for the Aids Programme of Research in South Africa, Durban, South Africa.
BMJ Open. 2022 Jan 6;12(1):e052880. doi: 10.1136/bmjopen-2021-052880.
Young African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution.
CAPRISA 018 is a phase I/II trial to evaluate the safety, acceptability, tolerability and pharmacokinetics (PKs) of a TAF subdermal silicone implant containing 110 mg of TAF with an anticipated 0.25 mg/day release rate.The phase I trial (n=60) will assess the safety of one implant inserted in six participants (Group 1), followed by dose escalation components (Groups 2 and 3) assessing the safety, tolerability and PK of one to four TAF 110 mg implants releasing between 0.25 mg and 1 mg daily in 54 healthy women at low risk for HIV infection. Data from this phase I trial will be used to determine the dosing, implant location and implant replacement interval for the phase II trial.The phase II component (Group 4) will assess extended safety, PK, tolerability and acceptability of the implant in 490 at risk women, randomised in a 1:1 ratio to the TAF implant and placebo tablet or to the placebo implant and an oral pre-exposure prophylaxis tablet. Safety will be assessed by calculating the percentage change in creatinine clearance from baseline at weeks 4, 12, 24, 36, 72, 96 and 120, compared with the percentage change in the control group.
The South African Health Products Regulatory Authority and the University of KwaZulu-Natal's Biomedical Research Ethics Committee have approved the trial. Results will be disseminated through open access peer reviewed publications, conference presentations, public stakeholder engagement and upload of data into the clinical trials registry.
PACTR201809520959443.
年轻的非洲女性感染 HIV 的风险极高。我们需要能够赋予女性保护自己能力的 HIV 技术。替诺福韦艾拉酚胺（TAF）等安全、有效的抗逆转录病毒药物，制成长效皮下植入剂，为我们提供了一种创新的解决方案。
CAPRISA 018 是一项 I/II 期临床试验，旨在评估替诺福韦艾拉酚胺皮下硅胶植入剂的安全性、可接受性、耐受性和药代动力学（PK）。该植入剂含有 110mg 的 TAF，预计以 0.25mg/天的速度释放。I 期临床试验（n=60）将评估 6 名参与者中 1 个植入物的安全性（第 1 组），随后进行剂量递增部分（第 2 组和第 3 组），评估 54 名感染 HIV 风险低的健康女性中 1 至 4 个 TAF 110mg 植入物的安全性、耐受性和 PK，这些植入物以 0.25mg 至 1mg/天的速度释放。I 期临床试验的数据将用于确定 II 期临床试验的剂量、植入部位和植入物更换间隔。II 期部分（第 4 组）将评估 490 名高危女性的延长安全性、PK、耐受性和可接受性，她们将以 1:1 的比例随机分配到 TAF 植入物和安慰剂片剂组或安慰剂植入物和口服暴露前预防片剂组。安全性将通过计算与对照组相比，第 4、12、24、36、72、96 和 120 周时从基线的肌酐清除率的百分比变化来评估。
南非卫生产品监管局和夸祖鲁-纳塔尔大学生物医学伦理委员会已批准该试验。结果将通过同行评议的开放获取出版物、会议演讲、公众利益相关者参与以及将数据上传到临床试验注册处来传播。
PACTR201809520959443。
