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Abstract：
BACKGROUND: COVID-19 remains a significant risk for the immunocompromised given their lower responsiveness to vaccination or infection. Therefore, passive immunity through long-acting monoclonal antibodies (mAbs) offers a needed approach for pre-exposure prophylaxis (PrEP). Our study evaluated safety, anti-SARS-CoV-2 neutralizing activity, nasal penetration, and pharmacokinetics (PK) of two half-life-extended investigational mAbs, AER001 and AER002, providing the first demonstration of upper airway penetration of mAbs with the LS-modification.
METHODS: This randomized, double-blind, placebo-controlled phase I study enrolled healthy adults (n = 80) who received two long-acting COVID mAbs (AER001 and AER002), AER002 alone, or placebo. The dose ranged from 100 mg (mg) to 1200 mg per mAb component. The primary objective was to describe the safety and tolerability following intravenous (IV) administration. Secondary objectives were to describe PK, anti-drug antibodies (ADA), neutralization activity levels, and safety evaluation through 6 months of follow-up.
RESULTS: The majority (97.6%) of the reported adverse events (AE) post administration were of grade 1 severity. There were no serious adverse events (SAE) or ADAs. AER001 and AER002 successfully achieved an extended half-life of 105 days and 97.5 days, respectively. Participants receiving AER001 and AER002 (300 mg each) or AER002 (300 mg) alone showed 15- and 26-fold higher neutralization levels against D614G and omicron BA.1 than the placebo group 24 h post-administration. Single 300 or 1200 mg IV dose of AER001 and AER002 resulted in nasal mucosa transudation of approximately 2.5% and 2.7%, respectively.
CONCLUSIONS: AER001 and AER002 showed an acceptable safety profile and extended half-life. High serum neutralization activity was observed against D614G and Omicron BA.1 compared to the placebo group. These data support that LS-modified mAbs can achieve durability, safety, potency, and upper airway tissue penetration and will guide the development of the next generation of mAbs for COVID-19 prevention and treatment.
BACKGROUND: EudraCT Number 2022-001709-35 (COV-2022-001).
METHODS: This randomized, double-blind, placebo-controlled phase I study enrolled healthy adults (n = 80) who received two long-acting COVID mAbs (AER001 and AER002), AER002 alone, or placebo. The dose ranged from 100 mg (mg) to 1200 mg per mAb component. The primary objective was to describe the safety and tolerability following intravenous (IV) administration. Secondary objectives were to describe PK, anti-drug antibodies (ADA), neutralization activity levels, and safety evaluation through 6 months of follow-up.
RESULTS: The majority (97.6%) of the reported adverse events (AE) post administration were of grade 1 severity. There were no serious adverse events (SAE) or ADAs. AER001 and AER002 successfully achieved an extended half-life of 105 days and 97.5 days, respectively. Participants receiving AER001 and AER002 (300 mg each) or AER002 (300 mg) alone showed 15- and 26-fold higher neutralization levels against D614G and omicron BA.1 than the placebo group 24 h post-administration. Single 300 or 1200 mg IV dose of AER001 and AER002 resulted in nasal mucosa transudation of approximately 2.5% and 2.7%, respectively.
CONCLUSIONS: AER001 and AER002 showed an acceptable safety profile and extended half-life. High serum neutralization activity was observed against D614G and Omicron BA.1 compared to the placebo group. These data support that LS-modified mAbs can achieve durability, safety, potency, and upper airway tissue penetration and will guide the development of the next generation of mAbs for COVID-19 prevention and treatment.
BACKGROUND: EudraCT Number 2022-001709-35 (COV-2022-001).
摘要：
背景：鉴于COVID-19对疫苗接种或感染的反应性较低，其免疫功能受损的风险仍然很大。因此,通过长效单克隆抗体(mAb)的被动免疫为暴露前预防(PrEP)提供了必要的方法.我们的研究评估了安全性，抗SARS-CoV-2中和活性，鼻腔渗透，和两个半衰期延长的研究性单克隆抗体的药代动力学（PK），AER001和AER002，首次证明了通过LS修饰的单克隆抗体的上呼吸道渗透。
方法：这是随机的，双盲,安慰剂对照I期研究招募了健康成年人(n=80)，他们接受了两种长效COVID单克隆抗体(AER001和AER002)，AER002单独,或安慰剂。每个mAb组分的剂量范围为100mg(mg)至1200mg。主要目的是描述静脉内(IV)给药后的安全性和耐受性。次要目标是描述PK，抗药物抗体（ADA），中和活性水平，并通过6个月的随访进行安全性评价。
结果：给药后报告的不良事件（AE）的大多数（97.6%）为1级严重程度。没有严重不良事件（SAE）或ADAs。AER001和AER002成功实现了105天和97.5天的延长半衰期，分别。单独接受AER001和AER002（各300mg）或AER002（300mg）的参与者在给药后24小时对D614G和omicronBA.1的中和水平比安慰剂组高15和26倍。AER001和AER002的单次300或1200mgIV剂量导致鼻粘膜渗出约2.5％和2.7％，分别。
结论：AER001和AER002显示出可接受的安全性和延长的半衰期。与安慰剂组相比,观察到针对D614G和OmicronBA.1的高血清中和活性。这些数据支持LS修饰的单克隆抗体可以实现耐久性，安全,效力，效力和上气道组织渗透，并将指导用于COVID-19预防和治疗的下一代单克隆抗体的开发。
背景：EudraCT编号2022-001709-35（COV-2022-001）。
方法：这是随机的，双盲,安慰剂对照I期研究招募了健康成年人(n=80)，他们接受了两种长效COVID单克隆抗体(AER001和AER002)，AER002单独,或安慰剂。每个mAb组分的剂量范围为100mg(mg)至1200mg。主要目的是描述静脉内(IV)给药后的安全性和耐受性。次要目标是描述PK，抗药物抗体（ADA），中和活性水平，并通过6个月的随访进行安全性评价。
结果：给药后报告的不良事件（AE）的大多数（97.6%）为1级严重程度。没有严重不良事件（SAE）或ADAs。AER001和AER002成功实现了105天和97.5天的延长半衰期，分别。单独接受AER001和AER002（各300mg）或AER002（300mg）的参与者在给药后24小时对D614G和omicronBA.1的中和水平比安慰剂组高15和26倍。AER001和AER002的单次300或1200mgIV剂量导致鼻粘膜渗出约2.5％和2.7％，分别。
结论：AER001和AER002显示出可接受的安全性和延长的半衰期。与安慰剂组相比,观察到针对D614G和OmicronBA.1的高血清中和活性。这些数据支持LS修饰的单克隆抗体可以实现耐久性，安全,效力，效力和上气道组织渗透，并将指导用于COVID-19预防和治疗的下一代单克隆抗体的开发。
背景：EudraCT编号2022-001709-35（COV-2022-001）。
