Tolerability, pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody, in Chinese healthy volunteers and psoriatic patients.
OBJECTIVE
To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.


METHODS
Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.


RESULTS
CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C(max) increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.


CONCLUSIONS
CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.
International Cancer Research Institute, Second Military Medical University, Shanghai 200433, China.
Xian-ping
XP
Li
Jing
J
Li
Heng
H
Yan
Bo
B
Zhou
Bo-hua
BH
Li
Wei-zhu
WZ
Qian
Sheng
S
Hou
Hao
H
Wang
Fei
F
Hao
Ya-jun
YJ
Guo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D040881:CD11a Antigen / Q000378:metabolism*; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D000911:Antibodies, Monoclonal; D040881:CD11a Antigen; D011994:Recombinant Proteins