title: First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.
abstract: This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17-19 d in the 3 highest dose groups and volume of distribution of 5-6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration.
authors.affiliation: a InterveXion Therapeutics , LLC ; Little Rock , AR USA.
authors.forename: Misty W
authors.initials: MW
authors.lastname: Stevens
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Henry
authors.forename: S Michael
authors.initials: SM
authors.lastname: Owens
authors.forename: Ralph
authors.initials: R
authors.lastname: Schutz
authors.forename: W Brooks
authors.initials: WB
authors.lastname: Gentry
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000276:immunology / Q000517:prevention & control; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics*; D000917:Antibody Formation / Q000276:immunology; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008694:Methamphetamine / Q000276:immunology*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D008694:Methamphetamine
keywords: AE, adverse event; AUC(0-inf), area under the concentration-time curve from 0 to infinity; CL, clearance; CTCAE, Common Terminology Criteria for Adverse Events; Cmax, maximum concentration; ECG, electrocardiogram; FDA, Food and Drug Administration; GLP, good laboratory practice; HACA, human anti-chimeric antibodies; KD, dissociation constant; METH, (+)methamphetamine; Vd, volume of distribution; addiction; chimeric antibody; first in human; healthy volunteers; mAb, monoclonal antibody; methamphetamine; monoclonal antibody; pharmacokinetics; t1/2, apparent terminal half-life