Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial.
Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial.
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DOI：
10.1136/bmjopen-2020-042247
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发表时间：
2020-11-26
期刊：
影响因子：
2.9
通讯作者：
Abdool Karim S
中科院分区：
文献类型：
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作者：
Mahomed S;Garrett N;Karim QA;Zuma NY;Capparelli E;Baxter C;Gengiah T;Archary D;Samsunder N;Doria-Rose N;Moore P;Williamson C;Barouch DH;Fast PE;Pozzetto B;Hankins C;Carlton K;Ledgerwood J;Morris L;Mascola J;Abdool Karim S
迫切需要新的艾滋病毒预防战略。广泛中和抗体（bNAb）的发现为评估被动免疫作为潜在预防策略和促进疫苗开发提供了机会。自2014年以来，已经从感染C进化枝的南非供体CAPRISA 256中分离出了几种bNAb。一种特殊的bNAb，CAP 256-VRC26.25，被发现是非常有效的，对C进化枝病毒，在撒哈拉以南非洲占主导地位的艾滋病毒进化枝具有良好的覆盖率。在非人灵长类动物中的挑战研究表明，即使在极低剂量下，这种抗体也具有完全保护作用。随后对该bNAb进行了结构改造，临床变体现在被称为CAP 256 V2 LS。CAPRISA 012 B是CAPRISA 012 bNAb试验计划中三项试验中的第二项。这是一项评估CAP 256 V2 LS安全性和药代动力学的首次人体I期研究。研究分为四组。第1组是向HIV阴性和HIV阳性女性静脉内施用的剂量递增的CAP 256 V2 LS。组2是在HIV阴性女性中皮下（SC）施用的剂量递增的CAP 256 V2 LS，其具有和不具有分散剂重组人透明质酸酶（rHuPH 20），作为单次或重复剂量。第3组和第4组为随机安慰剂对照组，以评估向HIV阴性女性SC施用的两种（CAP 256 V2 LS + VRC 07 - 523 LS; CAP 256 V2 LS + PGT 121）和三种（CAP 256 V2 LS + VRC 07 - 523 LS + PGT 121）bNAb组合。将通过与研究产品相关的反应原性和不良事件的频率评估安全性。将通过剂量亚组和给药途径评估CAP 256 V2 LS单独给药以及与VRC 07 - 523 LS和PGT 121联合给药的药代动力学分布。夸祖鲁-纳塔尔大学生物医学研究伦理委员会（BREC）和南非卫生产品监管局（SAHPRA）已授予监管批准（试验参考编号：BREC 00000857/2019和SAHPRA 20200123）。试验结果将通过会议报告、同行评审出版物和临床试验注册表传播。PACTR 202003767867253;预结果。
New HIV prevention strategies are urgently required. The discovery of broadly neutralising antibodies (bNAbs) has provided the opportunity to evaluate passive immunisation as a potential prevention strategy and facilitate vaccine development. Since 2014, several bNAbs have been isolated from a clade C-infected South African donor, CAPRISA 256. One particular bNAb, CAP256-VRC26.25, was found to be extremely potent, with good coverage against clade C viruses, the dominant HIV clade in sub-Saharan Africa. Challenge studies in non-human primates demonstrated that this antibody was fully protective even at extremely low doses. This bNAb was subsequently structurally engineered and the clinical variant is now referred to as CAP256V2LS. CAPRISA 012B is the second of three trials in the CAPRISA 012 bNAb trial programme. It is a first-in-human, phase I study to assess the safety and pharmacokinetics of CAP256V2LS. The study is divided into four groups. Group 1 is a dose escalation of CAP256V2LS administered intravenously to HIV-negative and HIV-positive women. Group 2 is a dose escalation of CAP256V2LS administered subcutaneously (SC), with and without the dispersing agent recombinant human hyaluronidase (rHuPH20) as single or repeat doses in HIV-negative women. Groups 3 and 4 are randomised placebo controlled to assess two (CAP256V2LS+VRC07-523LS; CAP256V2LS+PGT121) and three (CAP256V2LS+VRC07-523LS+PGT121) bNAb combinations administered SC to HIV-negative women. Safety will be assessed by the frequency of reactogenicity and adverse events related to the study product. Pharmacokinetic disposition of CAP256V2LS alone and in combination with VRC07-523LS and PGT121 will be assessed via dose subgroups and route of administration. The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and the South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval (trial reference numbers: BREC00000857/2019 and SAHPRA 20200123). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry. PACTR202003767867253; Pre-results.
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