A dose-searching trial of an anti-LFA1 monoclonal antibody in first kidney transplant recipients.
25.3, a mouse IgG1 monoclonal antibody (MoAb), directed at the alpha chain of the LFA1 molecule (CD11a) has been used in prophylaxis of rejection in recipients of cadaveric kidney graft. Promising clinical results have been obtained for both tolerance and efficacy [1]. The aim of this trial was to determine the optimal dosage, base on a pharmacokinetic-pharmacodynamic analysis of the data obtained from the 15 patients included in this dose-searching study. Biological parameters, such as circulating levels and functional inhibition (as detected in an adhesion assay of patient lymphocytes), were measured during and after treatment. A Hill relation was calculated between the effect and the concentration measured and led us to select a 15 mg/day dose for further clinical trials, with a loading dose of 30 mg. An additional group receiving this protocol was submitted to the same calculation, and the results from this last group were in agreement with this previous analysis.
Le Mauff
B
B
INSERM U437, Service de Néphrologie et Immunologie Clinique, Nantes, France.
Le Meur
Y
Y
Hourmant
M
M
Debray
M
M
Boeffard
F
F
Alberici
G
G
Soulillou
J P
JP
Scherrmann
J M
JM
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1