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Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease.
- Source :
-
Inflammatory bowel diseases [Inflamm Bowel Dis] 2010 Jul; Vol. 16 (7), pp. 1209-18. - Publication Year :
- 2010
-
Abstract
- Background: Interleukin-12 (IL-12) and interleukin-23 (IL-23) are inflammatory cytokines linked to the Th-1 and Th-17 phenotypes associated with Crohn's disease (CD). We investigated the activity and safety of apilimod mesylate (formerly STA-5326), an oral IL-12 and IL-23 inhibitor, in patients with active CD.<br />Methods: We performed a multicenter, Phase 2, randomized, double-blinded, placebo-controlled study to evaluate the efficacy of apilimod mesylate in treating 220 adult patients with moderate-to-severe CD (Crohn's Disease Activity Index [CDAI] score 220-450). Patients were stratified according to C-reactive protein (CRP) levels and corticosteroid use and were randomly assigned to receive placebo or apilimod mesylate 50 mg daily or 100 mg daily. The study was divided into an induction phase (43 days) and a maintenance phase (125 days). The primary analysis involved a comparison of the proportion of patients experiencing clinical response, defined as at least a 100-point decrease in CDAI score from baseline at day 29. Data on adverse events were also collected.<br />Results: In all, 220 of the planned 282 patients were enrolled when the Data Monitoring Committee determined that the drug was not efficacious as a treatment and closed enrollment. A clinical response was experienced by 18 patients (24.7%) in the 50-mg daily (QD) group (n = 73) and 19 patients (25.7%) in the 100 mg QD group (n = 74), as compared with 21 patients (28.8%) in the placebo group (n = 73) on day 29 (P = 0.71 for each comparison). No significant adverse safety signal was observed.<br />Conclusions: Apilimod was well-tolerated but did not demonstrate efficacy over placebo in patients with active CD.
- Subjects :
- Administration, Oral
Adolescent
Adult
Aged
Double-Blind Method
Female
Humans
Hydrazones
Male
Middle Aged
Placebo Effect
Pyrimidines
Quality of Life
Remission Induction
Treatment Outcome
Young Adult
Crohn Disease drug therapy
Interleukin-12 antagonists & inhibitors
Interleukin-23 antagonists & inhibitors
Morpholines therapeutic use
Triazines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4844
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Inflammatory bowel diseases
- Publication Type :
- Academic Journal
- Accession number :
- 19918967
- Full Text :
- https://doi.org/10.1002/ibd.21159