Clinical trial NCT01852825: MK-8237 (SCH900237) Biomarker Study in Participants With Allergic Rhinitis or Rhinoconjunctivitis (MK-8237-009)
Official title: A Two Part, Randomized Clinical Trial to Study Biomarkers of MK-8237 (SCH 900237) Treatment in Subjects With House Dust Mite Induced Allergic Rhinitis or Rhinoconjunctivitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Allergic Rhinitis
Allergic Rhinoconjunctivitis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: ALK-Abelló A/S
First posted: 2013-05-14
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to assess the effect on various biomarkers of treatment with MK-8237 in participants with allergic rhinitis or rhinoconjunctivitis. In Part 1 of the study healthy participants undergo nasal allergen challenge (NAC) with house dust mite (HDM) extract in order to verify the operational performance of NAC and associated sample collection methods. Part 2, the main study, is a placebo controlled, double blind study of participants with HDM-induced allergic rhinitis or rhinoconjunctivitis. The primary hypotheses are that the changes from baseline in post-allergen challenge HDM-specific Immunoglobulin G4 (IgG4) and Immunoglobulin E blocking factor (IgE-BF) are greater after treatment with MK-8237 than after treatment with placebo.


Eligibility criteria: Inclusion Criteria:

Part 1:

* healthy participants
* has a Body Mass Index (BMI) =\< 30 kg/m\^2
* female of reproductive potential remains abstinent or uses two acceptable methods of birth control from 2 weeks before first allergen challenge to 2 weeks after last allergen challenge; alternatively hormonal contraception may be used.

Part 2:

* has a Body Mass Index (BMI) =\< 38 kg/m\^2
* has a clinical history of allergic rhinitis/rhinoconjunctivitis to HDM for at least one year, and used medication to relieve symptoms within the last year
* does not have asthma, or has mild controlled asthma not requiring regular use over the 12 months prior to screening of any corticosteroids
* female of reproductive potential remains abstinent or use two acceptable methods of birth control from 2 weeks before first allergen challenge to at least 2 weeks after last allergen challenge or last dose of study drug, whichever is longer
* has not smoked or used tobacco for the prior 6 months, and agrees not to during study

Exclusion Criteria:

Parts 1 and 2:

* is experiencing at the first NAC visit, symptoms from an upper or lower respiratory tract infection (viral or bacterial)
* has participated within the prior 3 months in another investigational study (that included an investigational drug or agent)
* is directly associated with the administration of the study or is related to the investigational study staff
* is mentally or legally incapacitated, has significant emotional problems or has a history of clinically significant psychiatric disorder within the past 5 years
* has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
* has a history of cancer
* has a history of significant intolerability to drugs or food
* is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV
* had major surgery or lost 1 unit (500 mL) of blood within the prior 4 weeks
* has a clinical history of chronic sinusitis during the prior 2 years
* has any nasal condition (e.g. nasal polyposis) that could confound efficacy or safety assessments
* is pregnant or expects to conceive during the study period
* is a nursing mother
* consumes more than 3 glasses of alcoholic beverages per day
* regularly uses any illicit drug, or has a history of drug or alcohol abuse within the prior 6 months

Part 2 only:

* is experiencing allergic rhinoconjunctivitis exacerbation at Screening NAC
* consumes excessive daily amounts of caffeinated beverages
* has a known history of allergy, hypersensitivity or intolerance to investigational medicines
* is sensitized and regularly exposed to animal dander and molds in the home or workplace in a manner that might interfere with the study in the opinion of the investigator
* is sensitized and regularly exposed to seasonal allergens such as Birch or grass pollen (sensitized but out of season is acceptable however)
* has a history of chronic urticaria and/or angioedema within the prior 2 years
* has had previous immunotherapeutic treatment with any HDM allergen for more than 1 month during the prior 3 years
* is receiving any specific immunotherapy within prior 60 days
* has a history of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy due to an unknown cause or an inhalant allergen

Primary outcomes:
measure: Change From Baseline in D. Farinae HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in D. Pteronyssinus HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in HDM-specific IgE Blocking Factor (IgE-BF) in Serum at 12 Weeks
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change From Baseline in 6.5 Hours Post-NAC Interleukin-5 (IL-5) Protein Concentration in Nasal Exudates Following 12 Weeks of Treatment (Part 2)
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in 6.5 Hours Post-NAC Nasal Epithelial Eosinophil-related Messenger RNA (mRNA) Signature Following 12 Weeks of Treatment (Part 2)
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Time Weighted Average (TWA) Over 1 Hour Pre-NAC Through 1 Hour Post-NAC Visual Analog Score (VAS) for Sneezing, Rhinorrhea, Congestion and Nasal Itch Following 12 Weeks of Treatment (Part 2)
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Gunawardana NC, Zhao Q, Carayannopoulos LN, Tsai K, Malkov VA, Selverian D, Clarke G, Mant T, Butts BD, Lund K, Hansel TT, Nolte H. The effects of house dust mite sublingual immunotherapy tablet on immunologic biomarkers and nasal allergen challenge symptoms. J Allergy Clin Immunol. 2018 Feb;141(2):785-788.e9. doi: 10.1016/j.jaci.2017.08.016. Epub 2017 Sep 11. No abstract available.