First-in-Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID-19.
First-in-Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID-19.
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DOI：
10.1002/cpt.2405
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发表时间：
2021-12
影响因子：
6.7
通讯作者：
Benson C
中科院分区：
文献类型：
--
作者：
Chen P;Datta G;Grace Li Y;Chien J;Price K;Chigutsa E;Brown-Augsburger P;Poorbaugh J;Fill J;Benschop RJ;Rouphael N;Kay A;Mulligan MJ;Saxena A;Fischer WA;Dougan M;Klekotka P;Nirula A;Benson C
在大流行期间，迫切需要针对2019年冠状病毒病（COVID - 19）住院患者的治疗方法。Bamlanivimab是一种有效的中和性单克隆抗体，可阻止严重急性呼吸综合征冠状病毒2 （SARS - CoV - 2）附着和进入人体细胞，这可能会带来潜在的治疗效果。J2W‐MC‐PYAA是一项随机、双盲、赞助商非盲、安慰剂对照、单次递增剂量的首次人体试验（NCT04411628），在住院的COVID‐19患者中进行。总共有24名患者接受了安慰剂或单剂量的bamlanivimab （700 mg， 2800 mg或7000 mg）。主要目的是评估安全性和耐受性，包括不良事件和严重不良事件，其次是药代动力学（PK）和药效学分析。治疗紧急不良事件（TEAE）发生率在安慰剂组和联合巴兰尼韦单抗组中相同（66.7%）。teae的数量或严重程度没有明显的剂量相关增加。在研究期间没有发生严重的不良事件或死亡，也没有因不良事件而中断研究。巴兰尼韦单抗的PKs呈线性关系，单次静脉给药后暴露量随剂量成比例增加。半衰期为~ 17天。这些结果证明了bamlanivimab具有良好的安全性，并提供了安全性、耐受性和PKs的初步关键评估，支持了bamlanivimab在几项正在进行的临床试验中的发展。
Therapeutics for patients hospitalized with coronavirus disease 2019 (COVID‐19) are urgently needed during the pandemic. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. J2W‐MC‐PYAA was a randomized, double‐blind, sponsor unblinded, placebo‐controlled, single ascending dose first‐in‐human trial (NCT04411628) in hospitalized patients with COVID‐19. A total of 24 patients received either placebo or a single dose of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg). The primary objective was assessment of safety and tolerability, including adverse events and serious adverse events, with secondary objectives of pharmacokinetic (PK) and pharmacodynamic analyses. Treatment‐emergent adverse event (TEAE) rates were identical in the placebo and pooled bamlanivimab groups (66.7%). There were no apparent dose‐related increases in the number or severity of TEAEs. There were no serious adverse events or deaths during the study, and no discontinuations due to adverse events. PKs of bamlanivimab is linear and exposure increased proportionally with dose following single i.v. administration. The half‐life was ~ 17 days. These results demonstrate the favorable safety profile of bamlanivimab, and provided the initial critical evaluation of safety, tolerability, and PKs in support of the development of bamlanivimab in several ongoing clinical trials.
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DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
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作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
3.5
作者：
Jones, Hannah M.;Zhang, Zhiwei;Webster, Robert
通讯作者：
Webster, Robert
影响因子：
120.7
作者：
Li, Ling;Zhang, Wei;Liu, Zhong
通讯作者：
Liu, Zhong
影响因子：
15.9
作者：
Bronte, Vincenzo;Ugel, Stefano;Olivieri, Oliviero
通讯作者：
Olivieri, Oliviero