First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.
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.
['Stevens|Misty W|MW|', 'Henry|Ralph L|RL|', 'Owens|S Michael|SM|', 'Schutz|Ralph|R|', 'Gentry|W Brooks|WB|']
D000293:Adolescent D000328:Adult D019969:Amphetamine-Related Disorders D000911:Antibodies, Monoclonal D000917:Antibody Formation 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 D008875:Middle Aged D011993:Recombinant Fusion Proteins D013997:Time Factors D055815:Young Adult
monoclonal antibody healthy volunteers pharmacokinetics 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 mAb, monoclonal antibody methamphetamine t1/2, apparent terminal half-life