Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis.
Clin Pharmacol Ther
; 64(3): 339-46, 1998 Sep.
Article
en En
| MEDLINE
| ID: mdl-9757158
ABSTRACT
OBJECTIVE:
To evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of a humanized anti-CD11/CD18 monoclonal antibody (Hu23F2G) in patients with multiple sclerosis.METHODS:
In this phase I uncontrolled dose escalation study, patients (n = 24) with primary or secondary progressive multiple sclerosis received single intravenous infusions of Hu23F2G (0.01 to 4.0 mg/kg). Study parameters included safety, pharmacology, immunogenicity, and brain magnetic resonance imaging (MRI).RESULTS:
Hu23F2G had few adverse effects, but 2 cases of urinary tract infection and 2 cases of gingivitis did occur. Transient leukocytes developed in some subjects receiving > or = 1.0 mg/kg. The pharmacokinetic response was nonlinear, with the area under the curve increasing out of proportion to the increase in dose. The mean terminal half-life increased with dose and was 21.9 (SD, 12.8) hours at the 4.0 mg/kg dose. High saturation (> 80%) of CD11/CD18 on circulating leukocytes was achieved with doses > or = 0.2 mg/kg. The duration of high leukocyte saturation was dose-dependent, persisting for more than a week at the 4.0 mg/kg dose. A marked decrease in leukocyte migration in response to cutaneous inflammation was observed. Antibodies against Hu23F2G were not detected. The neurologic examinations were stable except for 1 subject who had worsening weakness associated with an infection. No significant changes were noted on brain MRI scans.CONCLUSIONS:
Hu23F2G was tolerated at doses that achieved high degrees of leukocyte CD11/CD118 saturation with in vivo inhibition of leukocyte migration. Because this phase I study was not designed to determine the clinical efficacy of Hu23F2G, further studies are needed.
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Banco de datos:
MEDLINE
Asunto principal:
Antígenos CD18
/
Antígenos CD11
/
Anticuerpos Monoclonales
/
Esclerosis Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Año:
1998
Tipo del documento:
Article