Pharmacokinetics, tolerability, and preliminary efficacy of human anti-Pseudomonas aeruginosa monoclonal antibodies in pneumonia and burn infection patients.
Human monoclonal antibody (hMAb) cocktail SM-17220 (also known as BT-570), a heterofunctional antibody mixture of 3 human IgM MAbs (HI-223, MH-4H7, and IN-2A8; ratio of 1:10:10) directed against Pseudomonas aeruginosa, were administered to patients with pneumonia or burn wounds (or both) to assess the pharmacokinetics, safety, antigenicity, and preliminary efficacy. Twenty mg of SM-17220 was IV infused over 60 min once daily on 3 consecutive days. Twenty patients (8 pneumonia, 4 burns, and 8 both) completed the study. SM-17220 was safe and well tolerated, and no subjects developed antibodies to SM-17220 and mouse J-chain during the follow-up of 8 weeks. Each MAb of SM-17220 had a half-life ranging from 49 to 91 h, similar to native human IgM. Both MH-4H7 and IN-2A8 administration resulted in a high serum level for about 4 days over an effective concentration, whereas HI-223 showed a lower serum level than expected. Some indications of a potential efficacy were observed and are discussed here.
Harrison
F J
FJ
Harrison Clinical Research GmbH, Munchen, Germany.
Rohm
D
D
Kohzuki
T
T
Noguchi
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002056:Burns / Q000378:metabolism* / Q000628:therapy; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008875:Middle Aged; D010865:Pilot Projects; D011014:Pneumonia / Q000378:metabolism* / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D000911:Antibodies, Monoclonal