tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2016 Jul 5. pii: AAC.00607-16. [Epub ahead of print]
[h=1]Two Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending-Dose Studies to Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza A Monoclonal Antibody, MHAA4549A, in Healthy Volunteers.[/h] Lim JJ[SUP]1[/SUP], Deng R[SUP]2[/SUP], Derby MA[SUP]2[/SUP], Larouche R[SUP]3[/SUP], Horn P[SUP]2[/SUP], Anderson M[SUP]2[/SUP], Maia M[SUP]2[/SUP], Carrier S[SUP]3[/SUP], Pelletier I[SUP]3[/SUP], Burgess T[SUP]2[/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] Hospitalized 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 strains. Two phase 1 trials examined the safety, tolerability, and pharmacokinetics of MHAA4549A in healthy volunteers.
[h=4]METHODS:[/h] 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 8400 mg or 10800 mg MHAA4549A or placebo. Subjects were followed for 120 days after dosing.
[h=4]RESULTS:[/h] 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 [MHAA4549A], 1/5 [placebo]; Trial 2: 4/8 [MHAA4549A], 2/6 [placebo]). MHAA4549A showed no relevant time- or dose-related changes in laboratory values or vital signs compared to placebo. No subjects developed an anti-therapeutic antibody response following MHAA4549A administration. MHAA4549A showed linear serum pharmacokinetics, with a mean half-life of 22.5-23.7 days.
[h=4]CONCLUSIONS:[/h] MHAA4549A is safe and well tolerated in healthy volunteers up to a single intravenous dose of 10800 mg and demonstrated 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 nos. NCT01877785 and NCT02284607).
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27381392 DOI: 10.1128/AAC.00607-16
[PubMed - as supplied by publisher]
[h=1]Two Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending-Dose Studies to Investigate the Safety, Tolerability, and Pharmacokinetics of an Anti-Influenza A Monoclonal Antibody, MHAA4549A, in Healthy Volunteers.[/h] Lim JJ[SUP]1[/SUP], Deng R[SUP]2[/SUP], Derby MA[SUP]2[/SUP], Larouche R[SUP]3[/SUP], Horn P[SUP]2[/SUP], Anderson M[SUP]2[/SUP], Maia M[SUP]2[/SUP], Carrier S[SUP]3[/SUP], Pelletier I[SUP]3[/SUP], Burgess T[SUP]2[/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] Hospitalized 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 strains. Two phase 1 trials examined the safety, tolerability, and pharmacokinetics of MHAA4549A in healthy volunteers.
[h=4]METHODS:[/h] 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 8400 mg or 10800 mg MHAA4549A or placebo. Subjects were followed for 120 days after dosing.
[h=4]RESULTS:[/h] 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 [MHAA4549A], 1/5 [placebo]; Trial 2: 4/8 [MHAA4549A], 2/6 [placebo]). MHAA4549A showed no relevant time- or dose-related changes in laboratory values or vital signs compared to placebo. No subjects developed an anti-therapeutic antibody response following MHAA4549A administration. MHAA4549A showed linear serum pharmacokinetics, with a mean half-life of 22.5-23.7 days.
[h=4]CONCLUSIONS:[/h] MHAA4549A is safe and well tolerated in healthy volunteers up to a single intravenous dose of 10800 mg and demonstrated 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 nos. NCT01877785 and NCT02284607).
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27381392 DOI: 10.1128/AAC.00607-16
[PubMed - as supplied by publisher]