tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2017 May 30. pii: AAC.00279-17. doi: 10.1128/AAC.00279-17. [Epub ahead of print]
[h=1]A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending-Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Monoclonal Antibody, MHAB5553A, in Healthy Volunteers.[/h] Lim JJ[SUP]1[/SUP], Derby MA[SUP]2[/SUP], Zhang Y[SUP]2[/SUP], Deng R[SUP]2[/SUP], Larouche R[SUP]3[/SUP], Anderson M[SUP]2[/SUP], Maia M[SUP]2[/SUP], Carrier S[SUP]3[/SUP], Pelletier I[SUP]3[/SUP], Girard J[SUP]3[/SUP], Kulkarni P[SUP]2[/SUP], Newton E[SUP]2[/SUP], Tavel JA[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] This Phase 1, randomized, double-blind, placebo-controlled, single ascending-dose study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of MHAB5553A. Twenty-six healthy male and female volunteers >18 years were randomized into five cohorts receiving a single intravenous (i.v.) dose of 120, 1200, 3600, 8400, or 10800 mg MHAB5553A or placebo (4 active: 1 placebo, except 120-mg cohort [4:2]). Subjects were followed for 120 days after dosing.
[h=4]RESULTS:[/h] 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 placebo. Observed serum PK was linear and generally dose-proportional and observed nasal PK was nonlinear and generally non-dose-proportional.
[h=4]CONCLUSIONS:[/h] MHAB5553A is generally well tolerated in healthy volunteers up to at least a single i.v. dose of 10800 mg and demonstrated linear serum PK consistent with those of a human IgG1 antibody lacking known endogenous targets in humans.
Copyright ? 2017 American Society for Microbiology.
PMID: 28559255 DOI: 10.1128/AAC.00279-17
[h=1]A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending-Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza B Monoclonal Antibody, MHAB5553A, in Healthy Volunteers.[/h] Lim JJ[SUP]1[/SUP], Derby MA[SUP]2[/SUP], Zhang Y[SUP]2[/SUP], Deng R[SUP]2[/SUP], Larouche R[SUP]3[/SUP], Anderson M[SUP]2[/SUP], Maia M[SUP]2[/SUP], Carrier S[SUP]3[/SUP], Pelletier I[SUP]3[/SUP], Girard J[SUP]3[/SUP], Kulkarni P[SUP]2[/SUP], Newton E[SUP]2[/SUP], Tavel JA[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] 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.
[h=4]METHODS:[/h] This Phase 1, randomized, double-blind, placebo-controlled, single ascending-dose study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of MHAB5553A. Twenty-six healthy male and female volunteers >18 years were randomized into five cohorts receiving a single intravenous (i.v.) dose of 120, 1200, 3600, 8400, or 10800 mg MHAB5553A or placebo (4 active: 1 placebo, except 120-mg cohort [4:2]). Subjects were followed for 120 days after dosing.
[h=4]RESULTS:[/h] 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 placebo. Observed serum PK was linear and generally dose-proportional and observed nasal PK was nonlinear and generally non-dose-proportional.
[h=4]CONCLUSIONS:[/h] MHAB5553A is generally well tolerated in healthy volunteers up to at least a single i.v. dose of 10800 mg and demonstrated linear serum PK consistent with those of a human IgG1 antibody lacking known endogenous targets in humans.
Copyright ? 2017 American Society for Microbiology.
PMID: 28559255 DOI: 10.1128/AAC.00279-17