Clinical trial NCT01644617: A Dose-Ranging Study of the Safety and Effectiveness of MK-8237 in the Treatment of House Dust Mite (HDM) Induced Allergic Rhinitis/Rhinoconjunctivitis in Adults (MK-8237-003/P07627)
Official title: A Phase IIb, Randomized, Placebo-Controlled, Dose-Finding Clinical Trial to Study the Safety and Efficacy of MK-8237 Using an Environmental Exposure Chamber in Subjects With House Dust Induced Allergic Rhinitis/Rhinoconjunctivitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rhinitis, Allergic, Perennial
Rhinitis, Allergic, Nonseasonal
Lead sponsor: ALK-Abelló A/S
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-07-19
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the dose-related effectiveness, the safety and the tolerability of MK-8237, compared to placebo, in the treatment of house dust mite (HDM)-induced allergic rhinitis/rhinoconjunctivitis in adults. The primary hypothesis is that administration of MK-8237, compared to placebo, results in dose-related improvement in the average total nasal symptom score (TNSS) determined during environmental exposure chamber (EEC) challenge.


Eligibility criteria: Inclusion Criteria:

* History of allergic rhinitis/rhinoconjunctivitis to house dust of 1 year duration or more (with or without asthma)
* If female of childbearing potential, has a negative urine pregnancy test at screening and agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control within the projected duration of the study.

Exclusion Criteria:

* Sensitized and regularly exposed to animal dander and molds, (e.g. present in the home, job, etc.)
* Sensitized and regularly exposed to seasonal allergens (i.e., birch or grass pollen)
* Immunosuppressive treatment within 3 months prior to screening (except steroids for allergic and asthma symptoms)
* History of chronic urticaria and/or angioedema within 2 years prior to screening
* Previous immunotherapy treatment with any HDM allergen for more than 1 month within 3 years prior to screening
* Ongoing treatment with any specific immunotherapy
* History of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, due to an unknown cause or to an inhalant allergen
* Unstable uncontrolled/partially controlled or severe asthma, or life-threatening asthma attack or an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids (but allowing short-acting beta agonists \[SABA\]) within 3 months prior to screening
* Asthma requiring medium- or high-dose inhaled corticosteroid (ICS) within 12 months prior to screening
* Chronic sinusitis within 2 years prior to screening
* Nasal condition that could confound the efficacy or safety assessments (e.g., nasal polyps)
* Pregnant, breastfeeding or planning to become pregnant during the study
* Participation in a different investigational study at any site during the same time frame of this study
* Direct association with the administration of the study or a family member of the study staff

Primary outcomes:
measure: Average Total Nasal Symptom Score (TNSS) During Environmental Exposure Chamber (EEC) Challenge Session at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Average TNSS During EEC Challenge Session at Week 16
timeFrame: Week 16
measure: Average TNSS During EEC Challenge Session at Week 8
timeFrame: Week 8
measure: Average Total Symptom Score (TSS [TNSS + TOSS]) During EEC Challenge Session at Week 24
timeFrame: Week 24
measure: Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 16
timeFrame: Week 16
measure: Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 8
timeFrame: Week 8
measure: Average Total Ocular Symptom Score (TOSS) During EEC Challenge Session at Week 24
timeFrame: Week 24
measure: Average TOSS During EEC Challenge Session at Week 16
timeFrame: Week 16
measure: Average TOSS During EEC Challenge Session at Week 8
timeFrame: Week 8
measure: HDM-specific Immunoglobulin E (IgE) Levels at Week 8
timeFrame: Week 8
measure: HDM-specific Immunoglobulin G4 (IgG4) Levels at Week 8
timeFrame: Week 8
measure: Change From Baseline in HDM-specific IgE Levels at Week 8
timeFrame: Baseline and Week 8
measure: Change From Baseline in HDM-specific IgG4 Levels at Week 8
timeFrame: Time Frame: Baseline and Week 8
measure: Percentage of Participants Who Experienced At Least One Adverse Event (AE)
timeFrame: From first dose to last dose of treatment plus 2 weeks of follow-up (Up to 26 weeks)
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE
timeFrame: From first dose to last dose of treatment (Up to 24 weeks)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Nolte H, Maloney J, Nelson HS, Bernstein DI, Lu S, Li Z, Kaur A, Zieglmayer P, Zieglmayer R, Lemell P, Horak F. Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber. J Allergy Clin Immunol. 2015 Jun;135(6):1494-501.e6. doi: 10.1016/j.jaci.2014.12.1911. Epub 2015 Jan 27.
citation: Fortescue R, Kew KM, Leung MST. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2020 Sep 14;9(9):CD011293. doi: 10.1002/14651858.CD011293.pub3.
citation: Roth-Walter F, Schmutz R, Mothes-Luksch N, Lemell P, Zieglmayer P, Zieglmayer R, Jensen-Jarolim E. Clinical efficacy of sublingual immunotherapy is associated with restoration of steady-state serum lipocalin 2 after SLIT: a pilot study. World Allergy Organ J. 2018 Oct 1;11(1):21. doi: 10.1186/s40413-018-0201-8. eCollection 2018.
citation: Bernstein DI, Kleine-Tebbe J, Nelson HS, Bardelas JA Jr, Sussman GL, Lu S, Rehm D, Svanholm Fogh B, Nolte H. SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration. Ann Allergy Asthma Immunol. 2018 Jul;121(1):105-110. doi: 10.1016/j.anai.2018.04.007. Epub 2018 Apr 12.
citation: Zieglmayer P, Nolte H, Nelson HS, Bernstein DI, Kaur A, Jacobi H, Lemell P, Schmutz R, Zieglmayer R, Horak F. Long-term effects of a house dust mite sublingual immunotherapy tablet in an environmental exposure chamber trial. Ann Allergy Asthma Immunol. 2016 Dec;117(6):690-696.e1. doi: 10.1016/j.anai.2016.10.015.