Dose-Finding Efficacy and Safety Trial of House Dust Mite Sublingual Immunotherapy Tablet, MK-8237, Using an Environmental Exposure Chamber
Tuesday, March 4, 2014: 2:15 PM
Room 8 (Convention Center)
Hendrik Nolte, MD, PhD, , , , , , ,
Rationale: Sublingual immunotherapy with house dust mite (HDM) might be beneficial in patients with allergic rhinitis with/without conjunctivitis (AR/C), although reported effect size is small to moderate and varies greatly among studies. MK-8237 (Merck/ALK-Abelló) is a sublingual HDM immunotherapy tablet currently under investigation.  

Methods: In this randomized, double-blind, single-site trial adults with HDM-induced AR/C with/without asthma (n=124) received daily MK-8237 12 DU, 6 DU, or placebo for 24 weeks, and underwent exposure challenges (Vienna Challenge Chamber) at weeks 8, 16, and 24. The primary objective was to evaluate the dose-related efficacy of MK-8237 versus placebo on total nasal symptom score (TNSS) during chamber challenge at week 24. TNSS was the sum of 4 nasal symptom scores (maximum=12).

Results: MK-8237 12 DU and 6 DU provided a 48.4% and 26.2% improvement, respectively, in TNSS at week 24 versus placebo (mean difference: −3.62, P< .001 and −1.98, P=.003). TNSS improvements were also observed at weeks 8 (mean difference: −1.37, 20.3%; P=.007) and 16 (mean difference: −2.08, 30.1%; P<.001) for the 12 DU dose and week 16 (mean difference: −1.23, 17.8%; P=.032) for the 6 DU dose. Total symptom scores (nasal+ocular symptoms) were significantly improved by both doses versus placebo at week 24. Both doses of MK-8237 were well tolerated, with no systemic allergic reactions or reactions requiring epinephrine.

Conclusions: MK-8237 appears promising, with potential for high and clinically meaningful (>20% reduction in symptoms) effect to be further evaluated in field trials. A dose-dependent effect was observed, with the 12 DU dose exhibiting the best benefit/risk ratio.