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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)

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ClinicalTrials.gov Identifier: NCT01644617
Recruitment Status : Completed
First Posted : July 19, 2012
Results First Posted : February 13, 2017
Last Update Posted : September 15, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
ALK-Abelló A/S

Tracking Information
First Submitted Date  ICMJE July 17, 2012
First Posted Date  ICMJE July 19, 2012
Results First Submitted Date  ICMJE December 20, 2016
Results First Posted Date  ICMJE February 13, 2017
Last Update Posted Date September 15, 2017
Study Start Date  ICMJE October 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
Average Total Nasal Symptom Score (TNSS) During Environmental Exposure Chamber (EEC) Challenge Session at Week 24 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2012)
Average Total Nasal Symptom Score (TNSS) During Environmental Exposure Chamber (EEC) Challenge Sessions [ Time Frame: 6 months ]
TNSS is the total of scores for 4 nasal symptoms (itchy nose, blocked nose, runny nose, and sneezing), each scored on a 4-point rating scale (0=no symptoms to 3=severe symptoms; TNSS range: 0 to 12 points).
Change History Complete list of historical versions of study NCT01644617 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
  • Average TNSS During EEC Challenge Session at Week 16 [ Time Frame: Week 16 ]
    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 16. 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 Week 16 TNSS was analyzed using the 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.
  • Average TNSS During EEC Challenge Session at Week 8 [ Time Frame: Week 8 ]
    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 8. 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 Week 8 TNSS was analyzed using the 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.
  • Average Total Symptom Score (TSS [TNSS + TOSS]) During EEC Challenge Session at Week 24 [ Time Frame: Week 24 ]
    The average total TSS included the evaluation of the 4 nasal symptoms of the TNSS (itchy nose, blocked nose, runny nose, and sneezing) plus the 2 ocular symptoms of the TOSS (gritty/feeling/red/itchy eyes and watery eyes). The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 24. TSS was the total of scores for the 4 nasal symptoms and 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TSS ranged from 0 to 18 points. The Week 24 TSS was analyzed using the ANCOVA model with treatment and baseline TSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 16 [ Time Frame: Week 16 ]
    The average total TSS included the evaluation of the 4 nasal symptoms of the TNSS (itchy nose, blocked nose, runny nose, and sneezing) plus the 2 ocular symptoms of the TOSS (gritty/feeling/red/itchy eyes and watery eyes). The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 16. TSS was the total of scores for the 4 nasal symptoms and 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TSS ranged from 0 to 18 points. The Week 16 TSS was analyzed using the ANCOVA model with treatment and baseline TSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • Average TSS (TNSS + TOSS) During EEC Challenge Session at Week 8 [ Time Frame: Week 8 ]
    The average total TSS included the evaluation of the 4 nasal symptoms of the TNSS (itchy nose, blocked nose, runny nose, and sneezing) plus the 2 ocular symptoms of the TOSS (gritty/feeling/red/itchy eyes and watery eyes). The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 8. TSS was the total of scores for the 4 nasal symptoms and 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TSS ranged from 0 to 18 points. The Week 8 TSS was analyzed using the ANCOVA model with treatment and baseline TSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • Average Total Ocular Symptom Score (TOSS) During EEC Challenge Session at Week 24 [ Time Frame: Week 24 ]
    The average total TOSS included the evaluation of 2 ocular symptoms: gritty/feeling/red/itchy eyes and watery eyes. The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 24. TOSS was the total of scores for the 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TOSS ranged from 0 to 6 points. The Week 24 TOSS was analyzed using the ANCOVA model with treatment and baseline TOSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TOSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • Average TOSS During EEC Challenge Session at Week 16 [ Time Frame: Week 16 ]
    The average total TOSS included the evaluation of 2 ocular symptoms: gritty/feeling/red/itchy eyes and watery eyes. The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 16. TOSS was the total of scores for the 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TOSS ranged from 0 to 6 points. The Week 16 TOSS was analyzed using the ANCOVA model with treatment and baseline TOSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TOSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • Average TOSS During EEC Challenge Session at Week 8 [ Time Frame: Week 8 ]
    The average total TOSS included the evaluation of 2 ocular symptoms: gritty/feeling/red/itchy eyes and watery eyes. The endpoint was based on participant diary entries over the last 4 hours of the EEC challenge session at Week 8. TOSS was the total of scores for the 2 ocular symptoms, each scored on a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). The total TOSS ranged from 0 to 6 points. The Week 8 TOSS was analyzed using the ANCOVA model with treatment and baseline TOSS as covariates and expressed as a least squares mean with 95% confidence interval. A decrease in TOSS for participants receiving either dose of MK-8237 compared to placebo indicated an improvement in symptoms.
  • HDM-specific Immunoglobulin E (IgE) Levels at Week 8 [ Time Frame: Week 8 ]
    Dermatophagoides pteronyssinus (D. pteronyssinus) and Dermatophagoides farinae (D. farinae) serum IgE levels were measured using the Immunocap® assay at Week 8. IgE levels were expressed in Log 10 scale kilo units/Liter (kU/L). Analysis was based on the analysis of variance parametric (ANOVA) model with treatment as the fixed effect and reported as mean IgE with a standard deviation.
  • HDM-specific Immunoglobulin G4 (IgG4) Levels at Week 8 [ Time Frame: Week 8 ]
    D. pteronyssinus and D. farinae serum IgG4 levels were measured using the Immunocap® assay at Week 8. IgG4 levels were expressed in Log 10 scale milligrams/Liter (mg/L). Analysis was based on the ANOVA model with treatment as the fixed effect and reported as mean IgG4 with a standard deviation.
  • Change From Baseline in HDM-specific IgE Levels at Week 8 [ Time Frame: Baseline and Week 8 ]
    D. pteronyssinus and D. farinae serum IgE levels were measured using the Immunocap® assay at baseline and Week 8. IgE levels were expressed in Log 10 scale kU/L. Mean Week 8 IgE levels were compared to the mean IgE levels at baseline. Analysis was based on the ANOVA model with treatment as the fixed effect and reported as a least squares mean with 95% confidence interval.
  • Change From Baseline in HDM-specific IgG4 Levels at Week 8 [ Time Frame: Time Frame: Baseline and Week 8 ]
    D. pteronyssinus and D. farinae serum IgG4 levels were measured using the Immunocap® assay at baseline and Week 8. IgG4 levels were expressed in Log 10 scale mg/L. Mean Week 8 IgG4 levels were compared to the mean IgG4 levels at baseline. Analysis was based on the ANOVA model with treatment as the fixed effect and reported as a least squares mean with 95% confidence interval.
  • Percentage of Participants Who Experienced At Least One Adverse Event (AE) [ Time Frame: From first dose to last dose of treatment plus 2 weeks of follow-up (Up to 26 weeks) ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
  • Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: From first dose to last dose of treatment (Up to 24 weeks) ]
    The percentage of participants who had study treatment stopped due to an AE. Discontinuations were reported for all randomized participants who received ≥1 dose of study treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2012)
  • Average Total Symptom Score (TSS) During EEC Challenge Sessions [ Time Frame: 6 months ]
    TSS is the sum of the TNSS and Total Ocular Symptom Score (TOSS). TOSS is the total of scores for 2 ocular symptom scores (gritty/feeling/red/itchy eyes and watery eyes), each scored on a 4-point scale (0=no symptoms to 3=severe symptoms; TOSS range: 0 to 6 points). (TSS range: 0 to 18 points).
  • Average Total Ocular Symptom Score (TOSS) During EEC Challenge Sessions [ Time Frame: 6 months ]
  • HDM-specific Immunoglobulin E (IgE) and HDM-specific Immunoglobulin G4 (IgG4) Levels [ Time Frame: Week 8 ]
  • Change from Pre-treatment in HDM-specific IgE and HDM-specific IgG4 Levels [ Time Frame: Pre-treatment (Week -6) and Week 8 ]
  • Number of Participants Who Experience At Least One Adverse Event (AE) [ Time Frame: From first dose of study drug through to 2 weeks after last dose of study drug (up to 26 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE A Phase IIb, Randomized, Placebo-Controlled, Dose-Finding Clinical Trial to Study the Safety and Efficacy of MK-8237 Using an Environmental Exposure Chamber in Subjects With House Dust Induced Allergic Rhinitis/Rhinoconjunctivitis
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Rhinitis, Allergic, Perennial
  • Rhinitis, Allergic, Nonseasonal
Intervention  ICMJE
  • Drug: Placebo
    Placebo rapidly dissolving tablets administered sublingually once daily
  • Drug: MK-8237 6 DU
    MK-8237 6 DU rapidly dissolving tablets administered sublingually once daily
    Other Name: SCH 900237
  • Drug: MK-8237 12 DU
    MK-8237 12 DU rapidly dissolving tablets administered sublingually once daily
    Other Name: SCH 900237
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo rapidly dissolving tablet administered sublingually once daily (q.d.), at approximately the same time each day, for 24 weeks
    Intervention: Drug: Placebo
  • Experimental: MK-8237 6 Developmental Units (DU)
    MK-8237 6 DU rapidly dissolving tablet administered sublingually q.d., at approximately the same time each day, for 24 weeks
    Intervention: Drug: MK-8237 6 DU
  • Experimental: MK-8237 12 DU
    MK-8237 12 DU rapidly dissolving tablet administered sublingually q.d., at approximately the same time each day, for 24 weeks
    Intervention: Drug: MK-8237 12 DU
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2013)
124
Original Estimated Enrollment  ICMJE
 (submitted: July 17, 2012)
120
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Austria
 
Administrative Information
NCT Number  ICMJE NCT01644617
Other Study ID Numbers  ICMJE P07627
2012-001855-38 ( EudraCT Number )
8237-003 ( Other Identifier: Merck Registration Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ALK-Abelló A/S
Study Sponsor  ICMJE ALK-Abelló A/S
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account ALK-Abelló A/S
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP