A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis.
Curr Med Res Opin
; 22(9): 1671-8, 2006 Sep.
Article
in En
| MEDLINE
| ID: mdl-16968570
ABSTRACT
OBJECTIVE:
To assess the safety, tolerability and pharmacokinetics of an interleukin (IL)-12/23 monoclonal antibody (mAb) in subjects with a relapsing form of multiple sclerosis (MS).METHODS:
A phase I, double-blind, placebo-controlled, sequential dose escalation study was conducted in 20 subjects with MS. Subjects were randomized (41) to receive a single subcutaneous injection of either IL-12/23 mAb (0.3, 0.75, 1.5, and 3.0 mg/kg) or placebo. Clinical and laboratory evaluations were performed through 16 weeks following administration.RESULTS:
IL-12/23 mAb was well tolerated in this study. Adverse events were generally mild or moderate, with no apparent dose-related trends. One subject with a family history of breast cancer was diagnosed during the study with breast cancer 21 days after IL-12/23 mAb administration. There were no significant changes in laboratory indicators of systemic or neurotoxicity. There was a large degree of variability in T2 lesion volume and total number of gadolinium-positive lesions, both unaffected by dose escalation. Three relapses of MS occurred in two placebo-treated subjects. Over the range of single doses studied, the median Tmax ranged from 9.0 to 16.5 days, and the median T1/2 ranged from 20.2 to 30.9 days.CONCLUSION:
Single subcutaneous administrations of IL-12/23 mAb in this first study of relapsing MS were generally well tolerated. Safety of the agent will need to be tested in a study of longer duration and involving a larger cohort of subjects.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-12 Subunit p40
/
Antibodies, Monoclonal
/
Multiple Sclerosis
Type of study:
Clinical_trials
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Curr Med Res Opin
Year:
2006
Document type:
Article
Affiliation country: