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

NCT ID: NCT02478398

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1025 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-20
• Study Completion Date: 2018-11-19

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Short ragweed pollen allergen extract

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.

Group Type: EXPERIMENTAL

Short ragweed pollen allergen extract

Intervention Type: BIOLOGICAL

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

Self-injectable epinephrine

Intervention Type: 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.

Albuterol/Salbutamol

Intervention Type: 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

Loratadine

Intervention Type: 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

Olopatadine

Intervention Type: DRUG

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

Mometasone furoate monohydrate

Intervention Type: 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

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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

Self-injectable epinephrine

Intervention Type: 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.

Albuterol/Salbutamol

Intervention Type: 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

Loratadine

Intervention Type: 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

Olopatadine

Intervention Type: DRUG

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

Mometasone furoate monohydrate

Intervention Type: 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

Interventions

Short ragweed pollen allergen extract

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: BIOLOGICAL

Self-injectable epinephrine

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.

Intervention Type: DRUG

Albuterol/Salbutamol

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

Intervention Type: DRUG

Loratadine

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

Intervention Type: DRUG

Olopatadine

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

Intervention Type: DRUG

Mometasone furoate monohydrate

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

Intervention Type: DRUG

Other Intervention Names

RAGWITEK™; MK-3641; EpiPen; ProAir HFA; Proventil HFA; Ventolin HFA; Claritin; Patanol; Nasonex

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 34886880 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32926419 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32548677 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32304832 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004341-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3641-008

Identifier Type: OTHER

Identifier Source: secondary_id

3641-008

Identifier Type: -

Identifier Source: org_study_id