Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV)(Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV))

概要

基本信息

药物类型

单克隆抗体

别名

Anti Flu Virus mAb40C7、Influenza monoclonal antibody 40C7、Monoclonal antibody against influenza A viruses

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靶点

hemagglutinin

作用机制

hemagglutinin调节剂(血凝素调节剂)

治疗领域

感染呼吸系统疾病

在研适应症-

非在研适应症

甲型流感病毒感染流感病毒感染

原研机构

AIMM Therapeutics BV

在研机构-

非在研机构

Janssen Pharmaceuticals, Inc.Crucell Holland B.V.Crucell Holdings, Inc.

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最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

6

项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的临床试验

EUCTR2013-003341-41-FR / Unknown statusN/AIIT

Multicenter, randomized, double-blind, placebo-controlled study to evaluate the effect of CR8020 and CR6261 in hospitalized patients with influenza A infection

开始日期2013-12-19

申办/合作机构

Crucell Holland B.V.

NCT02015533 / Withdrawn临床1期

A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Japanese Subjects to Assess the Safety, Pharmacokinetics and Immunogenicity of CR8020 Following Single Intravenous Administration

The purpose of the study is to assess the safety, pharmacokinetics (what the body does to the drug) and immunogenicity (ability of a particular substance to provoke an immune response in the human body) of CR8020 in japanese healthy participants

开始日期2013-12-01

申办/合作机构

Janssen Pharmaceuticals, Inc.

NCT01992276 / Withdrawn临床2期

Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of CR8020 and CR6261 in Hospitalized Patients With Influenza A Infection

The purpose of this study is to evaluate the rate of decline in quantitative viral load measured in hospitalized patients with Influenza A infection

开始日期2013-12-01

申办/合作机构

Crucell Holland B.V.

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100 项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的临床结果

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100 项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的转化医学

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100 项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的专利（医药）

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8

项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的文献（医药）

2016-12-01·Journal of Virology2区 · 医学

Human Monoclonal Antibody 81.39a Effectively Neutralizes Emerging Influenza A Viruses of Group 1 and 2 Hemagglutinins

2区 · 医学

Article

作者: Jones, Joyce ; Willis, Melissa ; Stevens, James ; Tan, Man-Wah ; Tegeris, John ; Marjuki, Henju ; Chai, Ning ; Mishin, Vasiliy P. ; Erlandson, Karl ; Davis, Todd ; Newton, Elizabeth M. ; Gubareva, Larisa V.

ABSTRACT The pandemic threat posed by emerging zoonotic influenza A viruses necessitates development of antiviral agents effective against various antigenic subtypes. Human monoclonal antibody (hMAb) targeting the hemagglutinin (HA) stalk offers a promising approach to control influenza virus infections. Here, we investigated the ability of the hMAb 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 HA subtypes. The majority of viruses were effectively neutralized by 81.39a at a 50% effective concentration (EC 50 ) of <0.01 to 4.9 μg/ml. Among group 2 HA viruses tested, a single A(H7N9) virus was not neutralized at 50 μg/ml; it contained HA 2 -Asp19Gly, an amino acid position previously associated with resistance to neutralization by the group 2 HA-neutralizing MAb CR8020. Notably, among group 1 HA viruses, H11-H13 and H16 subtypes were not neutralized at 50 μg/ml; they shared the substitution HA 2 -Asp19Asn/Ala. Conversely, H9 viruses harboring HA 2 -Asp19Ala were fully susceptible to neutralization. Therefore, amino acid variance at HA 2 -Asp19 has subtype-specific adverse effects on in vitro neutralization. Mice given a single injection (15 or 45 mg/kg of body weight) at 24 or 48 h after infection with recently emerged A(H5N2), A(H5N8), A(H6N1), or A(H7N9) viruses were protected from mortality and showed drastically reduced lung viral titers. Furthermore, 81.39a protected mice infected with A(H7N9) harboring HA 2 -Asp19Gly, although the antiviral effect was lessened. A(H1N1)pdm09-infected ferrets receiving a single dose (25 mg/kg) had reduced viral titers and showed less lung tissue injury, despite 24- to 72-h-delayed treatment. Taken together, this study provides experimental evidence for the therapeutic potential of 81.39a against diverse influenza A viruses. IMPORTANCE Zoonotic influenza viruses, such as A(H5N1) and A(H7N9) subtypes, have caused severe disease and deaths in humans, raising public health concerns. Development of novel anti-influenza therapeutics with a broad spectrum of activity against various subtypes is necessary to mitigate disease severity. Here, we demonstrate that the hemagglutinin (HA) stalk-targeting human monoclonal antibody 81.39a effectively neutralized the majority of influenza A viruses tested, representing 16 HA subtypes. Furthermore, delayed treatment with 81.39a significantly suppressed virus replication in the lungs, prevented dramatic body weight loss, and increased survival rates of mice infected with A(H5Nx), A(H6N1), or A(H7N9) viruses. When tested in ferrets, delayed 81.39a treatment reduced viral titers, particularly in the lower respiratory tract, and substantially alleviated disease symptoms associated with severe A(H1N1)pdm09 influenza. Collectively, our data demonstrated the effectiveness of 81.39a against both seasonal and emerging influenza A viruses.

2016-10-01·Drug Discovery Today2区 · 医学

Translating genomic sequences into antibody efficacy and safety against influenza toward clinical trial outcomes: a case study

2区 · 医学

Review

作者: Yang, Hong ; Yang, Hsih-Te ; Wang, Shih-Jon ; Chiang, Jung-Hsien

Antibodies (Abs) are regarded as a newly emerging form of therapeutics that can provide passive protection against influenza. Although the application of genomics in clinics has increased dramatically, the number of therapeutics available for the treatment of many diseases remains insufficient. To translate genomics into medicines, we established a computational workflow to reconstruct 3D structures of hemagglutinin [HA, antigen (Ag)] and Ab for modeling Ab-HA interactions, based on their protein sequences. This platform was capable of testing the validity of bioinformatics predictions against viral neutralization titers for four Abs: CH65, CR8020, C05, and 5J8. By considering off-target effects, CR8020, the only successful candidate in clinical trials, was prospectively identified. Our approach could facilitate the discovery of Ab drugs against infectious diseases.

2016-09-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Two Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Studies To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza A Virus Monoclonal Antibody, MHAA4549A, in Healthy Volunteers

2区 · 医学

Article

作者: Tavel, Jorge A. ; Anderson, Malia ; Lim, Jeremy J. ; Carrier, Stephanie ; Newton, Elizabeth ; Maia, Mauricio ; Burgess, Tracy ; Pelletier, Isabelle ; Horn, Priscilla ; Deng, Rong ; Larouche, Richard ; Kulkarni, Priya ; Derby, Michael A.

ABSTRACTHospitalized patients with severe influenza are at significant risk for morbidity and mortality. MHAA4549A is a human monoclonal immunoglobulin (Ig) G1 antibody that binds to a highly conserved stalk region of the influenza A virus hemagglutinin protein and neutralizes all tested seasonal human influenza A virus strains. Two phase 1 trials examined the safety, tolerability, and pharmacokinetics of MHAA4549A in healthy volunteers. Both single ascending-dose trials were randomized, double blinded, and placebo controlled. Trial 1 randomized 21 healthy adults into four cohorts receiving a single intravenous dose of 1.5, 5, 15, or 45 mg/kg MHAA4549A or placebo. Trial 2 randomized 14 healthy adults into two cohorts receiving a single intravenous fixed dose of 8,400 mg or 10,800 mg of MHAA4549A or placebo. Subjects were followed for 120 days after dosing. No subject was discontinued in either trial, and no serious adverse events were reported. The most common adverse event in both studies was mild headache (trial 1, 4/16 subjects receiving MHAA4549A and 1/5 receiving placebo; trial 2, 4/8 subjects receiving MHAA4549A and 2/6 receiving placebo). MHAA4549A produced no relevant time- or dose-related changes in laboratory values or vital signs compared to those with placebo. No subjects developed an antitherapeutic antibody response following MHAA4549A administration. MHAA4549A showed linear serum pharmacokinetics, with a mean half-life of 22.5 to 23.7 days. MHAA4549A is safe and well tolerated in healthy volunteers up to a single intravenous dose of 10,800 mg and demonstrates linear serum pharmacokinetics consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (These trials have been registered at ClinicalTrials.gov under registration no. NCT01877785 and NCT02284607).

100 项与 Monoclonal antibody against influenza A viruses(AIMM Therapeutics BV) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
流感病毒感染	临床2期	英国	Crucell Holland B.V.	2013-10-02
流感病毒感染	临床2期	英国	Crucell Holdings, Inc.	2013-10-02
流感病毒感染	临床2期	英国	Crucell Holdings, Inc.	2013-10-02
流感病毒感染	临床2期	英国	Crucell Holland B.V.	2013-10-02
甲型流感病毒感染	临床2期	-	AIMM Therapeutics BV	-
甲型流感病毒感染	临床2期	-	AIMM Therapeutics BV	-
甲型流感病毒感染	临床2期	-	Crucell Holdings, Inc.	-
甲型流感病毒感染	临床2期	-	Crucell Holdings, Inc.	-