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

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

doi:10.1128/aac.00607-16

Cited by 35 publications

(37 citation statements)

References 27 publications

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“…Currently, mAbs have been approved or are in development for numerous infectious diseases, including RSV, influenza, Pseudomonas aeruginosa, and Staphylococcus aureus (18,20,(29)(30)(31)(32). These mAbs target secreted virulence factors, surface/structural proteins, or both, resulting in neutralization of pathogen-induced host damage and improved pathogen clearance.…”

Section: Discussionmentioning

confidence: 99%

Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4

Cohen¹,

Pelletier²,

Cheng³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4

Cohen¹,

Pelletier²,

Cheng³

et al. 2017

JCI Insight

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“…MHAB5553A demonstrated linear serum PK consistent with typical human IgG1 antibodies with no known endogenous targets in humans (30), such as RG7667, an anticytomegalovirus antibody (31,32), and MHAA4549A (26,29,41). MHAB5553A serum PK resembled that of MHAA4549A, which had terminal half-lives of approximately 21 to 25 days and clearances of 151 to 204 ml/day for the same dose range in phase 1 studies in healthy volunteers (26).…”

Section: Discussionmentioning

confidence: 78%

“…MHAB5553A serum PK resembled that of MHAA4549A, which had terminal half-lives of approximately 21 to 25 days and clearances of 151 to 204 ml/day for the same dose range in phase 1 studies in healthy volunteers (26). Based on the totality of the data ( Fig.…”

Section: Discussionmentioning

confidence: 92%

“…The human efficacious dose of MHAB5553A is expected to be the same as that for MHAA4549A, a broadly neutralizing monoclonal IgG1 antibody that targets influenza A virus HA (25,26), based upon their similar mechanisms of action, comparable in vitro binding properties, comparable PK in mice and monkeys, and the same efficacious dose range in mouse influenza infection models (23,25,27,28). MHAA4549A also demonstrated strong antiviral activity at 3,600 mg in healthy volunteers challenged with influenza A virus (29).…”

Section: Discussionmentioning

confidence: 99%

“…Since MHAB5553A is a monoclonal antibody, it is metabolized through catabolic pathways, unlike small-molecule neuraminidase inhibitors. As a result, MHAB5553A is not expected to have drug-drug interactions with neuraminidase inhibitors like oseltamivir (26,39).…”

Section: Discussionmentioning

confidence: 99%

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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Virus Monoclonal Antibody, MHAB5553A, in Healthy Volunteers

Lim¹,

Derby²,

Zhang³

et al. 2017

Antimicrob Agents Chemother

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Influenza B can cause significant morbidity and mortality. MHAB5553A, a human monoclonal immunoglobulin G1 (IgG1) antibody that binds to a highly conserved region of the hemagglutinin protein of influenza B virus, is being examined as a novel therapeutic for the treatment of influenza B patients with severe disease. This phase 1, randomized, double-blind, placebo-controlled, single-ascendingdose study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of MHAB5553A. Twenty-six healthy male and female volunteers of Ͼ18 years of age were randomized into five cohorts receiving a single intravenous (i.v.) dose of 120, 1,200, 3,600, 8,400, or 10,800 mg MHAB5553A or placebo (four active:one placebo, except for the 120-mg cohort [4:2]). Subjects were followed for 120 days after dosing. No subject discontinued the study, no dose-limiting adverse events or serious adverse events were reported, and a maximum tolerated dose (MTD) was not defined. The most commonly reported adverse events were cold symptoms and headache; most were mild and occurred at a similar rate across all cohorts. MHAB5553A showed no relevant time-or dose-related changes in laboratory values or vital signs compared to the placebo. The observed serum PK was linear and generally dose proportional, and the observed nasal PK was nonlinear and generally non-dose proportional. MHAB5553A is generally well tolerated in healthy volunteers up to at least a single i.v. dose of 10,800 mg and demonstrated linear serum PK consistent with those of a human IgG1 antibody lacking known endogenous targets in humans. (This study has been registered at ClinicalTrials.gov under registration no. NCT02528903.)

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Antiviral Drugs Against Influenza Virus

Planz¹

2021

New Drug Development for Known and Emerging Viruses

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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

Cited by 35 publications

References 27 publications

Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4

Anti-LPS antibodies protect against Klebsiella pneumoniae by empowering neutrophil-mediated clearance without neutralizing TLR4

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Virus Monoclonal Antibody, MHAB5553A, in Healthy Volunteers

Antiviral Drugs Against Influenza Virus

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