Clinical trial NCT02478398: Efficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008)
Official title: A Phase III, Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of MK-3641, a Ragweed (Ambrosia Artemisiifolia) Sublingual Immunotherapy Tablet, in Children With a History of Ragweed-Induced Rhinoconjunctivitis With or Without Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rhinitis, Allergic, Seasonal
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 1025
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of short ragweed pollen allergen extract (MK-3641, SCH 039641, RAGWITEK™) sublingual immunotherapy tablets in children aged 5 to 17 years with ragweed-induced allergic rhinitis/rhinoconjunctivitis with or without asthma. The primary hypothesis of this study is that administration of short ragweed pollen allergen extract sublingual immunotherapy tablets to children 5 to 17 years of age, compared with placebo, will result in a significant reduction in the combination of rhinoconjunctivitis symptoms and medication use over the peak ragweed season (RS).


Eligibility criteria: Inclusion Criteria:

* Is between the ages of 4 and 17 years (inclusive) at enrollment in this study and is at least 5 years old at randomization
* Has a clinical history of significant ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis of ≥1 year (at least 1 season for ages 4 to 6 years) or ≥2 years (at least 2 seasons for ages 7 to 17 years) duration diagnosed by a physician (with or without asthma) and have received treatment for the condition during the previous ragweed season
* If female, agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control within the projected duration of the study.

Exclusion Criteria:

* Has a clinical history of symptomatic seasonal allergic rhinitis (and/or asthma) due to another allergen, which has required regular medication during, or potentially overlapping, the ragweed season
* Has a clinical history of significant symptomatic perennial allergic rhinitis and/or asthma due to an allergen to which the subject is regularly exposed during the ragweed season which would interfere with assessment of the treatment effect
* Has any nasal condition that could confound the efficacy or safety assessments (e.g., nasal polyposis).
* Has asthma requiring high daily doses of inhaled corticosteroids within the 6 months prior to the Screening visit
* Is either \>7 years old and cannot perform reproducible FEV1 maneuvers despite coaching; OR is ≤7 years old and cannot perform reproducible FEV1 maneuvers despite coaching and has current symptoms of asthma characterized by recurrent episodes of wheezing, or episodes of cough, wheeze, difficulty in breathing, or chest tightness
* Has severe, unstable, or uncontrolled asthma, as judged by the clinical investigator, or has experienced a 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) at any time within the last 3 months prior to the Screening or Randomization visits
* Has a history of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause, or inhalant allergen
* Has a diagnosis of eosinophilic esophagitis
* Has a history of chronic urticaria and/or chronic angioedema
* Has a clinical history of chronic sinusitis during the 2 years prior to the Screening or Randomization visits
* Has current severe atopic dermatitis
* Has a history of allergy, hypersensitivity, or intolerance to the ingredients of the study drug (except for Ambrosia artemisiifolia), rescue medications, or self-injectable epinephrine
* Has previously received short ragweed pollen allergen extract
* Has previously been randomized into this study
* Is participating in any other clinical study or plans to participate in another clinical study during the duration of this study

Primary outcomes:
measure: Total Combined Score (TCS) During the Peak Ragweed Season (RS)
timeFrame: The 15-day period during the ragweed season with the highest moving pollen average
Secondary outcomes:
measure: Average TCS During the Entire RS
timeFrame: Up to 13 weeks
measure: Average Rhinoconjunctivitis (RC) DSS During the Peak RS
timeFrame: The 15-day period during the ragweed season with the highest moving pollen average
measure: Average Rhinoconjunctivitis (RC) DMS During the Peak RS
timeFrame: The 15-day period during the ragweed season with the highest moving pollen average
measure: Percentage of Participants Reporting Pre-specified Local Application Site Reactions
timeFrame: Up to 35 weeks
measure: Percentage of Participants Reporting Anaphylaxis and/or Systemic Allergic Reactions
timeFrame: Up to 35 weeks
measure: Percentage of Participants Treated With Epinephrine
timeFrame: Up to 35 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Ellis AK, Gagnon R, Bernstein DI, Nolte H. Randomized controlled trial of ragweed sublingual immunotherapy tablet in the subpopulation of Canadian children and adolescents with allergic rhinoconjunctivitis. Allergy Asthma Clin Immunol. 2021 Dec 9;17(1):127. doi: 10.1186/s13223-021-00626-2.
citation: Fortescue R, Kew KM, Leung MST. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2020 Sep 14;9(9):CD011293. doi: 10.1002/14651858.CD011293.pub3.
citation: Field K, Blaiss MS. Sublingual Versus Subcutaneous Immunotherapy for Allergic Rhinitis: What Are the Important Therapeutic and Real-World Considerations? Curr Allergy Asthma Rep. 2020 Jun 16;20(9):45. doi: 10.1007/s11882-020-00934-4.
citation: Nolte H, Bernstein DI, Nelson HS, Ellis AK, Kleine-Tebbe J, Lu S. Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial. J Allergy Clin Immunol Pract. 2020 Jul-Aug;8(7):2322-2331.e5. doi: 10.1016/j.jaip.2020.03.041. Epub 2020 Apr 15.