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

NCT01852825 | Completed Phase 1 Results

• 2 other identifiers: 8237-0092012-005621-70
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in D. Farinae HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)

  Blood was collected from participants treated with Dermatophagoides (D.) farinae HDM and then with MK-8237 or placebo, and the amount of HDM-specific IgG4 antibodies in serum at baseline and at week 12 were measured. Fold change from baseline was evaluated based on constrained longitudinal data analysis (cLDA) method with log transformed data. The model included time (categorical variable), treatment, and time by treatment interaction as fixed effects and participants as random effect. Least squares geometric means are presented. It is hypothesized that the change from baseline is statistically greater with MK-8237 treatment than with placebo. This hypothesis is supported if the lower bound of the two-sided 90% confidence interval for the geometric mean fold difference is \>1.0.

  Baseline and 12 weeks

• Change From Baseline in D. Pteronyssinus HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)

  Blood was collected from participants treated with D. pteronyssinus HDM, and then with MK-8237 or placebo, and the amount of HDM-specific IgG4 antibodies in serum at baseline and at week 12 were measured. Fold change from baseline was evaluated based on cLDA method with log transformed data. The model included time (categorical variable), treatment, and time by treatment interaction as fixed effects and participants as random effect. Least squares geometric means are presented. It is hypothesized that the change from baseline is statistically greater with MK-8237 treatment than with placebo. This hypothesis is supported if the lower bound of the two-sided 90% confidence interval for the geometric mean fold difference is \>1.0.

  Baseline and 12 weeks

• Change From Baseline in HDM-specific IgE Blocking Factor (IgE-BF) in Serum at 12 Weeks

  Blood was collected from participants treated with D. pteronyssinus and D.farinae HDM and then with either MK-8237 or placebo, and the amount of IgE-BF in serum was measured based on an Ordinary IgE measurement and an assay in the presence of Competitors; with IgE-BF = 1 - (Competitive IgE/Ordinary IgE). This ranges from 0 (no IgE blocked) to 1 (all IgE blocked); and as it is based on a ratio there are no units. Change from baseline (12 weeks minus baseline) was evaluated based on cLDA method, and was analyzed based on the original scale. The model included time (categorical variable), treatment, and time by treatment interaction as fixed effects and participants as random effect. It is hypothesized that the change from baseline is statistically greater with MK-8237 treatment than with placebo. This hypothesis is supported if the lower bound of the 1-tailed 95% CI around the 12 week mean difference in change from baseline in HDM-specific IgE blocking factor response excludes zero.

  Baseline and 12 weeks

Secondary Outcomes (3)

• 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)

  Baseline and 12 weeks

• Change From Baseline in 6.5 Hours Post-NAC Nasal Epithelial Eosinophil-related Messenger RNA (mRNA) Signature Following 12 Weeks of Treatment (Part 2)

  Baseline and 12 weeks

• 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)

  Baseline and 12 weeks

Study Arms (3)

NAC + MK-8237 (Part 2)

EXPERIMENTAL

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)

Biological: MK-8237; Biological: NAC

NAC + Placebo (Part 2)

PLACEBO COMPARATOR

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)

Other: Placebo; Biological: NAC

NAC (Part 1)

EXPERIMENTAL

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

Biological: NAC

Interventions

MK-8237 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 + MK-8237 (Part 2)

Placebo OTHER

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

NAC + Placebo (Part 2)

NAC 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); NAC + MK-8237 (Part 2); NAC + Placebo (Part 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Related Publications (1)

• 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.

  PMID: 28911971 RESULT

MeSH Terms

Conditions

Rhinitis, Allergic

Condition Hierarchy (Ancestors)

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2013
• First Posted: May 14, 2013
• Study Start: November 27, 2013
• Primary Completion: July 20, 2015
• Study Completion: August 3, 2015
• Last Updated: March 15, 2019
• Results First Posted: February 13, 2017

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share