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Trial record 11 of 30 for:    Dermatophagoides pteronyssinus AND Dermatophagoides farinae

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

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ClinicalTrials.gov Identifier: NCT01852825
Recruitment Status : Completed
First Posted : May 14, 2013
Results First Posted : February 13, 2017
Last Update Posted : March 15, 2019
Sponsor:
Collaborator:
ALK-Abelló A/S
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Diagnostic
Conditions Allergic Rhinitis
Allergic Rhinoconjunctivitis
Interventions Biological: MK-8237
Other: Placebo
Biological: NAC
Enrollment 26
Recruitment Details In Part 1, healthy participants aged 18-55 years were enrolled; In Part 2, participants with house dust mite (HDM)-induced allergic rhinitis or rhinoconjunctivitis, aged 18-55, were enrolled.
Pre-assignment Details  
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description 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) 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) Nasal Allergen Challenge (NAC) treatment 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
Period Title: Overall Study
Started 16 7 3
Completed 14 7 3
Not Completed 2 0 0
Reason Not Completed
Withdrawal by Subject             2             0             0
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1) Total
Hide Arm/Group Description 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) 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) Nasal Allergen Challenge (NAC) treatment 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 Total of all reporting groups
Overall Number of Baseline Participants 16 7 3 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 7 participants 3 participants 26 participants
31.3  (8.6) 36.1  (13.2) 25.7  (4.0) 31.9  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 7 participants 3 participants 26 participants
Female
8
  50.0%
3
  42.9%
1
  33.3%
12
  46.2%
Male
8
  50.0%
4
  57.1%
2
  66.7%
14
  53.8%
1.Primary Outcome
Title Change From Baseline in D. Farinae HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 14 7 0
Geometric Mean (95% Confidence Interval)
Unit of Measure: Fold Change
0.392
(0.249 to 0.615)
0.166
(0.097 to 0.285)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments The hypothesis is supported if the lower bound of the two-sided 90% confidence interval for the Week 12 geometric mean fold difference is >1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 2.355
Confidence Interval (2-Sided) 90%
1.515 to 3.661
Estimation Comments MK-8237 treatment divided by Placebo treatment
2.Primary Outcome
Title Change From Baseline in D. Pteronyssinus HDM-specific IgG4 Antibodies in Serum at 12 Weeks (Part 2)
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 14 7 0
Geometric Mean (95% Confidence Interval)
Unit of Measure: Fold Change
0.619
(0.397 to 0.966)
0.284
(0.164 to 0.490)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments The hypothesis is supported if the lower bound of the two-sided 90% confidence interval for the Week 12 geometric mean fold difference is >1.0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 2.182
Confidence Interval (2-Sided) 90%
1.364 to 3.490
Estimation Comments MK-8237 treatment divided by Placebo treatment
3.Primary Outcome
Title Change From Baseline in HDM-specific IgE Blocking Factor (IgE-BF) in Serum at 12 Weeks
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 14 7 0
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Ratio
0.097
(-0.032 to 0.226)
-0.141
(-0.317 to 0.035)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments The hypothesis is supported if the lower bound of the 1-tailed 95% CI around the mean difference in change from baseline excludes zero
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.238
Confidence Interval (2-Sided) 90%
0.066 to 0.410
Estimation Comments MK-8237 treatment minus Placebo treatment
4.Secondary Outcome
Title 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)
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 14 6 0
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Fold change
9.444
(3.852 to 23.153)
8.843
(2.245 to 34.836)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.935
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.068
Confidence Interval (2-Sided) 90%
0.272 to 4.190
Estimation Comments MK-8237 treatment divided by Placebo treatment
5.Secondary Outcome
Title Change From Baseline in 6.5 Hours Post-NAC Nasal Epithelial Eosinophil-related Messenger RNA (mRNA) Signature Following 12 Weeks of Treatment (Part 2)
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 9 4 0
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Fold change
2.618
(0.911 to 5.160)
0.981
(0.267 to 3.610)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.296
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 2.210
Confidence Interval (2-Sided) 90%
0.605 to 8.066
Estimation Comments MK-8237 treatment divided by Placebo treatment
6.Secondary Outcome
Title 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)
Hide Description A visual analog scale (VAS) representing the spectrum of symptoms from absent (0) to extremely severe (100) for each of rhinorrhea, nasal blockage, sneezing and nasal itch were summed to obtain an overall score. The range of VAS overall score is 0 - 400, with higher numbers representing worse symptoms. The models for the time-weighted mean (TWA) of the summed scores over 1 hour pre-NAC through hour 1 following NAC were constructed at the original scale.
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants from Part 2 who are compliant with the study procedures and have available data from at least one treatment. Participants from Part 1 were not analyzed because they were not treated with MK-8237 or placebo.
Arm/Group Title NAC + MK-8237 (Part 2) NAC + Placebo (Part 2) NAC (Part 1)
Hide Arm/Group Description:
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)
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)
Nasal Allergen Challenge (NAC) treatment 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
Overall Number of Participants Analyzed 14 6 0
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
53.065
(25.797 to 80.334)
114.180
(74.723 to 153.638)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC + MK-8237 (Part 2), NAC + Placebo (Part 2)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Constrained Longitudinal Data Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -61.115
Confidence Interval (2-Sided) 90%
-100.185 to -22.045
Estimation Comments MK-8237 treatment minus Placebo treatment
Time Frame Part 1: Up to 17 days after treatment; Part 2: Up to 101 days after treatment
Adverse Event Reporting Description All participants who received at least one dose of the investigational drug.
 
Arm/Group Title NAC (Part 1) NAC + MK-8237 (Part 2) NAC + Placebo (Part 2)
Hide Arm/Group Description Nasal Allergen Challenge (NAC) treatment 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 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) 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)
All-Cause Mortality
NAC (Part 1) NAC + MK-8237 (Part 2) NAC + Placebo (Part 2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
NAC (Part 1) NAC + MK-8237 (Part 2) NAC + Placebo (Part 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/16 (0.00%)      0/7 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
NAC (Part 1) NAC + MK-8237 (Part 2) NAC + Placebo (Part 2)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      14/16 (87.50%)      6/7 (85.71%)    
Ear and labyrinth disorders       
Ear pruritus  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Eye disorders       
Conjunctivitis allergic  1  0/3 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Gastrointestinal disorders       
Dyspepsia  1  0/3 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Gastrooesophageal reflux disease  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Hypoaesthesia oral  1  0/3 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Lip pain  1  0/3 (0.00%)  0 2/16 (12.50%)  3 0/7 (0.00%)  0
Lip swelling  1  0/3 (0.00%)  0 3/16 (18.75%)  3 0/7 (0.00%)  0
Mouth swelling  1  0/3 (0.00%)  0 4/16 (25.00%)  8 0/7 (0.00%)  0
Oral pruritus  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Paraesthesia oral  1  0/3 (0.00%)  0 3/16 (18.75%)  6 1/7 (14.29%)  1
Swollen tongue  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Tongue pruritus  1  0/3 (0.00%)  0 4/16 (25.00%)  6 0/7 (0.00%)  0
General disorders       
Chest discomfort  1  0/3 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Immune system disorders       
Hypersensitivity  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Seasonal allergy  1  0/3 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Infections and infestations       
Conjunctivitis  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Upper respiratory tract infection  1  0/3 (0.00%)  0 6/16 (37.50%)  7 4/7 (57.14%)  5
Injury, poisoning and procedural complications       
Burns first degree  1  0/3 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Investigations       
Blood iron decreased  1  0/3 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  0/3 (0.00%)  0 1/16 (6.25%)  1 0/7 (0.00%)  0
Nervous system disorders       
Headache  1  0/3 (0.00%)  0 1/16 (6.25%)  1 1/7 (14.29%)  1
Respiratory, thoracic and mediastinal disorders       
Dry throat  1  0/3 (0.00%)  0 2/16 (12.50%)  2 0/7 (0.00%)  0
Nasal dryness  1  0/3 (0.00%)  0 0/16 (0.00%)  0 1/7 (14.29%)  1
Throat irritation  1  0/3 (0.00%)  0 3/16 (18.75%)  5 3/7 (42.86%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01852825     History of Changes
Other Study ID Numbers: 8237-009
2012-005621-70 ( EudraCT Number )
First Submitted: May 9, 2013
First Posted: May 14, 2013
Results First Submitted: December 20, 2016
Results First Posted: February 13, 2017
Last Update Posted: March 15, 2019