MK-8237 (SCH900237) Biomarker Study in Participants With Allergic Rhinitis or Rhinoconjunctivitis (MK-8237-009)

NCT ID: NCT01852825

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-27
• Study Completion Date: 2015-08-03

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.

Conditions

Allergic Rhinitis; Allergic Rhinoconjunctivitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

NAC + MK-8237 (Part 2)

Nasal Allergen Challenge (NAC) treatment consisting of 1800 Biological Units (BU) of HDM extract on Days -14, 56 and 84; starting on Day 1 a single tablet of MK-8237 with 12 Development Units (DUs), administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

Group Type: EXPERIMENTAL

MK-8237

Intervention Type: BIOLOGICAL

A single tablet of MK-8237 with 12 DU, administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

NAC

Intervention Type: BIOLOGICAL

0.1 mL fixed volume of 10,000 BU/mL of HDM extract is delivered with a Pfeiffer Bidose Nasal Delivery System (or equivalent) to each nostril for a total dose of 1800 BU at the start of Part 1; and in Part 2 on Days -14, 56 and 84

NAC + Placebo (Part 2)

NAC treatment consisting of 1800 BU of HDM extract on Days -14, 56 and 84; starting on Day 1 a single placebo tablet administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

A single placebo tablet administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

NAC

Intervention Type: BIOLOGICAL

0.1 mL fixed volume of 10,000 BU/mL of HDM extract is delivered with a Pfeiffer Bidose Nasal Delivery System (or equivalent) to each nostril for a total dose of 1800 BU at the start of Part 1; and in Part 2 on Days -14, 56 and 84

NAC (Part 1)

Nasal Allergen Challenge (NAC) consisting of 100 µl fixed volume of 10,000 biological units (BU) of HDM extract delivered with a Pfeiffer Bidose Nasal Delivery System (or equivalent) to each nostril for a total dose of 1800 BU at the start of Part 1

Group Type: EXPERIMENTAL

NAC

Intervention Type: BIOLOGICAL

0.1 mL fixed volume of 10,000 BU/mL of HDM extract is delivered with a Pfeiffer Bidose Nasal Delivery System (or equivalent) to each nostril for a total dose of 1800 BU at the start of Part 1; and in Part 2 on Days -14, 56 and 84

Interventions

MK-8237

A single tablet of MK-8237 with 12 DU, administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

Intervention Type: BIOLOGICAL

Placebo

A single placebo tablet administered sublingually, at approximately the same time each day for 84 days (+/- 5 days)

Intervention Type: OTHER

NAC

0.1 mL fixed volume of 10,000 BU/mL of HDM extract is delivered with a Pfeiffer Bidose Nasal Delivery System (or equivalent) to each nostril for a total dose of 1800 BU at the start of Part 1; and in Part 2 on Days -14, 56 and 84

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ALK-Abelló A/S

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 28911971 (View on PubMed)

Other Identifiers

2012-005621-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8237-009

Identifier Type: -

Identifier Source: org_study_id