White Joleen T, Terstappen Jonne, Levi Micha, Radivojevic Andrijana, Noble Robert, Anderson Aparna B, Wise-Blackman Gwendolyn, Dunne Michael W
Bill & Melinda Gates Medical Research Institute, Cambridge, MA, USA.
Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
BMC Infect Dis. 2024 Dec 18;24(1):1403. doi: 10.1186/s12879-024-10196-4.
Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries. To evaluate the ability of dried blood collection to generate data sets and conclusions comparable to serum collection, we compared pharmacokinetics (PK) of RSM01, immunogenicity, and virus neutralisation for dried capillary blood samples with serum samples.
RSM01 PK, anti-drug antibodies (ADA), and RSV-neutralising antibodies from the Phase 1 trial were analyzed and compared between matched serum and dried blood samples. Deming regression analysis was performed using baseline-corrected values to evaluate correlation between measurements in liquid serum versus dried blood.
The analysis showed good correlation (R > 0.95) between individual RSM01 concentrations measured in both serum and capillary blood. Analysis of RSM01 PK parameters in capillary blood yielded equivalent conclusions as from serum. A strong correlation (R > 0.95) was observed between RSV neutralising activity measured in both serum and capillary blood. In addition, RSV neutralising activity was correlated with RSM01 concentrations in both serum and capillary blood data sets. For ADA, individual sample results had 96% agreement (290/302) and overall participant ADA status had 93% agreement (52/56).
Both RSM01 concentrations and RSV neutralising activity showed a strong correlation between the serum and blood measurements. ADA measurements also had an agreement of > 90% for individual samples and overall participant status. Our results demonstrate that dried blood is a suitable specimen type for collection and evaluation in the RSM01 clinical development program and shows promise as a useful approach to reduce patient burden in clinical trials, particularly for infants in low- and middle-income countries.
Clinicaltrials.gov NCT05118386 November 12, 2021.
血清中的病毒中和抗体被认为是呼吸道合胞病毒（RSV）疫苗和单克隆抗体保护作用的关键相关指标。RSM01是一种新型、高效、半衰期延长且全人源的靶向RSV融合前F蛋白的单克隆抗体候选药物。目前处于1期开发阶段，RSM01主要致力于在低收入和中等收入国家潜在地提供一种有效且经济实惠的RSV预防策略。为了评估干血采集生成与血清采集可比的数据集和结论的能力，我们比较了RSM01的药代动力学（PK）、免疫原性以及干毛细血管血样与血清样本的病毒中和情况。
对1期试验中的RSM01 PK、抗药抗体（ADA）和RSV中和抗体在匹配的血清和干血样本之间进行分析和比较。使用基线校正值进行Deming回归分析，以评估液体血清与干血测量值之间的相关性。
分析显示血清和毛细血管血中测量的个体RSM01浓度之间具有良好的相关性（R > 0.95）。对毛细血管血中RSM01 PK参数的分析得出了与血清等效的结论。在血清和毛细血管血中测量的RSV中和活性之间观察到强相关性（R > 0.95）。此外，RSV中和活性与血清和毛细血管血数据集中的RSM01浓度相关。对于ADA，个体样本结果的一致性为96%（290/302），总体参与者ADA状态的一致性为93%（52/56）。
RSM01浓度和RSV中和活性在血清和血液测量之间显示出强相关性。ADA测量在个体样本和总体参与者状态方面的一致性也超过90%。我们的结果表明，干血是RSM01临床开发项目中适合采集和评估的样本类型，并有望成为减轻临床试验中患者负担的有用方法，特别是对于低收入和中等收入国家的婴儿。
Clinicaltrials.gov NCT05118386，2021年11月12日。
