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)

NCT01644617 | Completed Phase 2 Results

• 3 other identifiers: P076272012-001855-388237-003
• Study Type: interventional
• Target: 124
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Nonseasonal

Outcome Measures

Primary Outcomes (1)

• Average Total Nasal Symptom Score (TNSS) During Environmental Exposure Chamber (EEC) Challenge Session at Week 24

  The average total TNSS included the evaluation of 4 nasal symptoms: itchy nose, blocked nose, runny nose, and sneezing. The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 24. TNSS was the total of scores for the 4 nasal symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TNSS ranged from 0 to 12 points. The 24-week TNSS was analyzed using the analysis of covariance (ANCOVA) model with treatment and baseline TNSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TNSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.

  Week 24

Secondary Outcomes (14)

• Average TNSS During EEC Challenge Session at Week 16

  Week 16

• Average TNSS During EEC Challenge Session at Week 8

  Week 8

• Average Total Symptom Score (TSS [TNSS + TOSS]) During EEC Challenge Session at Week 24

  Week 24

• Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 16

  Week 16

• Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 8

  Week 8

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo rapidly dissolving tablet administered sublingually once daily (q.d.), at approximately the same time each day, for 24 weeks

Drug: Placebo

MK-8237 6 Developmental Units (DU)

EXPERIMENTAL

MK-8237 6 DU rapidly dissolving tablet administered sublingually q.d., at approximately the same time each day, for 24 weeks

Drug: MK-8237 6 DU

MK-8237 12 DU

EXPERIMENTAL

MK-8237 12 DU rapidly dissolving tablet administered sublingually q.d., at approximately the same time each day, for 24 weeks

Drug: MK-8237 12 DU

Interventions

Placebo DRUG

Placebo rapidly dissolving tablets administered sublingually once daily

Placebo

MK-8237 6 DU DRUG

MK-8237 6 DU rapidly dissolving tablets administered sublingually once daily

Also known as: SCH 900237

MK-8237 6 Developmental Units (DU)

MK-8237 12 DU DRUG

MK-8237 12 DU rapidly dissolving tablets administered sublingually once daily

Also known as: SCH 900237

MK-8237 12 DU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ALK-Abelló A/S: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (5)

• 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.

  PMID: 25636947 BACKGROUND

• 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.

  PMID: 32926419 DERIVED

• 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.

  PMID: 30323863 DERIVED

• 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.

  PMID: 29656145 DERIVED

• 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.

  PMID: 27979028 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic, Perennial

Condition Hierarchy (Ancestors)

Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 19, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 15, 2017
• Results First Posted: February 13, 2017

Record last verified: 2017-09