Efficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008)

NCT02478398 | Completed Phase 3 Results DMC

• 3 other identifiers: 3641-0082014-004341-27MK-3641-008
• Study Type: interventional
• Target: 1,025
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Rhinitis, Allergic, Seasonal

Outcome Measures

Primary Outcomes (1)

• Total Combined Score (TCS) During the Peak Ragweed Season (RS)

  TCS is daily symptom score (DSS) plus daily medication score (DMS), assessed in the peak RS (15 consecutive RS days with the highest 15-day average pollen count). The rhinoconjunctivitis (RC) DSS assesses 6 allergy symptoms measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Lower DSS indicates less RC symptoms. The RC DMS is based on use of RC rescue medications (loratadine, olopatadine, mometasone), with different rescue medications being assigned different scores/dose unit (score range: 0-20). Lower DMS indicates less RC medication use. Summed RC DSS+DMS could range from 0 to 38; a lower score indicates less RC symptoms and medication use. Components that contribute to DSS and DMS endpoints are collected in an electronic diary (e-diary) completed by the participant/parent/guardian. Evaluation is based on average TCS during peak RS.

  The 15-day period during the ragweed season with the highest moving pollen average

Secondary Outcomes (6)

• Average TCS During the Entire RS

  Up to 13 weeks

• Average Rhinoconjunctivitis (RC) DSS During the Peak RS

  The 15-day period during the ragweed season with the highest moving pollen average

• Average Rhinoconjunctivitis (RC) DMS During the Peak RS

  The 15-day period during the ragweed season with the highest moving pollen average

• Percentage of Participants Reporting Pre-specified Local Application Site Reactions

  Up to 35 weeks

• Percentage of Participants Reporting Anaphylaxis and/or Systemic Allergic Reactions

  Up to 35 weeks

Study Arms (2)

Short ragweed pollen allergen extract

EXPERIMENTAL

Participants receive one sublingual tablet containing 12 units of Ambrosia artemisiifolia major allergen number 1 (Amb a 1-U), once daily (QD) for up to 35 weeks. Participants may use study-provided rescue medication(s) as needed to treat rhinoconjunctivitis symptoms.

Biological: Short ragweed pollen allergen extract; Drug: Self-injectable epinephrine; Drug: Albuterol/Salbutamol; Drug: Loratadine; Drug: Olopatadine; Drug: Mometasone furoate monohydrate

Placebo

PLACEBO COMPARATOR

Participants receive one placebo sublingual tablet, QD for up to 35 weeks. Participants may use study-provided rescue medication(s) as needed to treat rhinoconjunctivitis symptoms.

Biological: Placebo; Drug: Self-injectable epinephrine; Drug: Albuterol/Salbutamol; Drug: Loratadine; Drug: Olopatadine; Drug: Mometasone furoate monohydrate

Interventions

Short ragweed pollen allergen extract BIOLOGICAL

One sublingual tablet containing 12 units of Amb a 1-U, once daily (QD) for up to 35 weeks.

Also known as: RAGWITEK™, MK-3641

Short ragweed pollen allergen extract

Placebo BIOLOGICAL

One placebo sublingual tablet, QD for up to 35 weeks.

Placebo

Self-injectable epinephrine DRUG

Intramuscular (IM) injection with suggested doses of 0.15 mg for participants weighing 15-30 kg (33-66 pounds) or 0.3 mg for participants weighing ≥30 kg (≥66 pounds), as needed for severe allergic reactions. Epinephrine was only provided in countries/study sites where it was a regulatory requirement.

Also known as: EpiPen

Placebo; Short ragweed pollen allergen extract

Albuterol/Salbutamol DRUG

Inhalation of albuterol 90 mcg/puff or salbutamol 100 mcg/puff metered dose inhaler (MDI), as needed as asthma rescue medication for those participants with asthma

Also known as: ProAir HFA, Proventil HFA, Ventolin HFA

Placebo; Short ragweed pollen allergen extract

Loratadine DRUG

5 mg (1 mg/mL syrup or 5 mg tablet) for participants 5 years old or 10 mg (1 mg/mL syrup or 10 mg tablet) for participants 6 to 17 years old, as needed for rhinoconjunctivitis symptoms

Also known as: Claritin

Placebo; Short ragweed pollen allergen extract

Olopatadine DRUG

Opthalmic solution, 1 drop (0.1%) per affected eye twice daily (BID), as needed for rhinoconjunctivitis symptoms

Also known as: Patanol

Placebo; Short ragweed pollen allergen extract

Mometasone furoate monohydrate DRUG

Intranasal spray, at doses of 1 spray (50 mcg/ spray) per nostril for participants 5 to 11 years old or 2 sprays (50 mcg/spray) per nostril for participants 12 to 17 years old, as needed for rhinoconjunctivitis symptoms

Also known as: Nasonex

Placebo; Short ragweed pollen allergen extract

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• 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.

  PMID: 34886880 DERIVED

• 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.

  PMID: 32926419 DERIVED

• 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.

  PMID: 32548677 DERIVED

• 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.

  PMID: 32304832 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic, Seasonal

Interventions

Epinephrine; Albuterol; Loratadine; Olopatadine Hydrochloride; Mometasone Furoate

Condition Hierarchy (Ancestors)

Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenethylamines; Ethylamines; Cyproheptadine; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Dibenzoxepins; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2015
• First Posted: June 23, 2015
• Study Start: July 20, 2015
• Primary Completion: November 9, 2018
• Study Completion: November 19, 2018
• Last Updated: September 6, 2019
• Results First Posted: July 9, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share