Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease.
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.


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.


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.


CONCLUSIONS
Apilimod was well-tolerated but did not demonstrate efficacy over placebo in patients with active CD.
Sands
Bruce E
BE
MGH Crohn's & Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. bsands@partners.org
Jacobson
Eric W
EW
Sylwestrowicz
Thomas
T
Younes
Ziad
Z
Dryden
Gerald
G
Fedorak
Richard
R
Greenbloom
Susan
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006835:Hydrazones; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D015990:Placebo Effect; D011743:Pyrimidines; D011788:Quality of Life; D012074:Remission Induction; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*; D055815:Young Adult
D006835:Hydrazones; D053759:Interleukin-23; D009025:Morpholines; D011743:Pyrimidines; D014227:Triazines; D018664:Interleukin-12; C504227:apilimod