Back to resultsEfficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008)
Primary Purpose
Rhinitis, Allergic, Seasonal
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Short ragweed pollen allergen extract
Placebo
Self-injectable epinephrine
Albuterol/Salbutamol
Loratadine
Olopatadine
Mometasone furoate monohydrate
Sponsored by
About this trial
This is an interventional treatment trial for Rhinitis, Allergic, Seasonal
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Short ragweed pollen allergen extract
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Average TCS During the Entire RS
TCS is DSS plus DMS, assessed here during the entire RS. This starts from the first day of 3 consecutive days with ragweed pollen counts ≥10 grains/m^3 through the last day of the last occurrence of 3 consecutive days with ragweed pollen counts ≥10 grains/m^3. The duration of the entire RS is up to 13 weeks; this duration varies by site/region. The RC DSS assesses 6 allergy symptoms measured on a scale of 0 to 3 (score range: 0-18). A lower DSS indicates less RC symptoms. The RC DMS is based on use of RC rescue medications (loratadine, olopatadine, mometasone) with different scores/dose unit (score range: 0-20). A lower DMS indicates less RC medication use. The sum of RC DSS+DMS ranges from 0 to 38, with a lower score indicating less RC symptoms and medication use. Components contributing to the TCS for the entire RS are collected in an e-diary completed by the participant/parent/guardian.
Average Rhinoconjunctivitis (RC) DSS During the Peak RS
The DSS consists of a total of 6 rhinoconjunctivitis symptoms: 4 rhinitis symptoms (runny nose, stuffy nose, sneezing, itchy nose) and 2 conjunctivitis symptoms (itchy eyes, watery eyes). The components that contribute to the DSS endpoint are collected in an e-diary completed by the participant/parent/guardian. The RC DSS is measured on a 4-point scale from 0 to 3 as follows: 0 (no sign/symptom evident) to 3 (sign/symptom that is hard to tolerate; may cause interference with activities of daily living and/or sleeping). The maximum DSS is 18 points if a participant experiences all 6 symptoms with an intensity of 3 for each symptom. The minimum DSS is 0 points if a participant experiences no symptoms. A lower DSS means symptoms are less severe. The evaluation is based on the average DSS during the peak RS.
Average Rhinoconjunctivitis (RC) DMS During the Peak RS
This DMS endpoint consists of a total of scores for use of RC medications: loratadine syrup or tablets (6 points), olopatadine (6 points), and mometasone (8 points). The score range of the RC DMS is 0-20 points, and a lower DMS means that less medication is used. The method used for analysis of the RC DMS is a zero-inflated log-normal model, which takes the average RC DMS during the peak RS as the response and adjusts for the same terms as in the ANOVA model. The components that contribute to the DMS endpoint are collected in an e-diary completed by the participant/parent/guardian.
Percentage of Participants Reporting Pre-specified Local Application Site Reactions
Pre-specified local application site reactions, irrespective of causality, included AEs related to lip swelling/edema, mouth swelling/edema, palatal swelling/edema, swollen tongue/edema, oropharyngeal swelling/edema, pharyngeal edema/throat tightness, oral pruritus, throat irritation, tongue pruritus, and ear pruritus.
Percentage of Participants Reporting Anaphylaxis and/or Systemic Allergic Reactions
For the purposes of this study, systemic allergic reactions are allergic reactions that occur away from the site of study drug application (allergic reactions other than local application site reactions). Anaphylaxis is a severe allergic reaction that typically involves more than one body system.
Percentage of Participants Treated With Epinephrine
Self-injectable epinephrine was provided to each participant/parent/guardian at randomization in countries where it is a regulatory requirement, and was to be available around the time treatment is administered at home. Self-injectable epinephrine was intended for immediate self-administration for an anaphylactic reaction, including symptoms/signs of upper airway obstruction. Instances of treatment with forms of epinephrine other than systemic epinephrine (e.g., inhaled racepinephrine) were counted as use of epinephrine.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02478398
Brief Title
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
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
July 20, 2015 (Actual)
Primary Completion Date
November 9, 2018 (Actual)
Study Completion Date
November 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhinitis, Allergic, Seasonal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1025 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Short ragweed pollen allergen extract
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Short ragweed pollen allergen extract
Other Intervention Name(s)
RAGWITEK™, MK-3641
Intervention Description
One sublingual tablet containing 12 units of Amb a 1-U, once daily (QD) for up to 35 weeks.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
One placebo sublingual tablet, QD for up to 35 weeks.
Intervention Type
Drug
Intervention Name(s)
Self-injectable epinephrine
Other Intervention Name(s)
EpiPen
Intervention Description
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
Intervention Name(s)
Albuterol/Salbutamol
Other Intervention Name(s)
ProAir HFA, Proventil HFA, Ventolin HFA
Intervention Description
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
Intervention Name(s)
Loratadine
Other Intervention Name(s)
Claritin
Intervention Description
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
Intervention Name(s)
Olopatadine
Other Intervention Name(s)
Patanol
Intervention Description
Opthalmic solution, 1 drop (0.1%) per affected eye twice daily (BID), as needed for rhinoconjunctivitis symptoms
Intervention Type
Drug
Intervention Name(s)
Mometasone furoate monohydrate
Other Intervention Name(s)
Nasonex
Intervention Description
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
Primary Outcome Measure Information:
Title
Total Combined Score (TCS) During the Peak Ragweed Season (RS)
Description
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.
Time Frame
The 15-day period during the ragweed season with the highest moving pollen average
Secondary Outcome Measure Information:
Title
Average TCS During the Entire RS
Description
TCS is DSS plus DMS, assessed here during the entire RS. This starts from the first day of 3 consecutive days with ragweed pollen counts ≥10 grains/m^3 through the last day of the last occurrence of 3 consecutive days with ragweed pollen counts ≥10 grains/m^3. The duration of the entire RS is up to 13 weeks; this duration varies by site/region. The RC DSS assesses 6 allergy symptoms measured on a scale of 0 to 3 (score range: 0-18). A lower DSS indicates less RC symptoms. The RC DMS is based on use of RC rescue medications (loratadine, olopatadine, mometasone) with different scores/dose unit (score range: 0-20). A lower DMS indicates less RC medication use. The sum of RC DSS+DMS ranges from 0 to 38, with a lower score indicating less RC symptoms and medication use. Components contributing to the TCS for the entire RS are collected in an e-diary completed by the participant/parent/guardian.
Time Frame
Up to 13 weeks
Title
Average Rhinoconjunctivitis (RC) DSS During the Peak RS
Description
The DSS consists of a total of 6 rhinoconjunctivitis symptoms: 4 rhinitis symptoms (runny nose, stuffy nose, sneezing, itchy nose) and 2 conjunctivitis symptoms (itchy eyes, watery eyes). The components that contribute to the DSS endpoint are collected in an e-diary completed by the participant/parent/guardian. The RC DSS is measured on a 4-point scale from 0 to 3 as follows: 0 (no sign/symptom evident) to 3 (sign/symptom that is hard to tolerate; may cause interference with activities of daily living and/or sleeping). The maximum DSS is 18 points if a participant experiences all 6 symptoms with an intensity of 3 for each symptom. The minimum DSS is 0 points if a participant experiences no symptoms. A lower DSS means symptoms are less severe. The evaluation is based on the average DSS during the peak RS.
Time Frame
The 15-day period during the ragweed season with the highest moving pollen average
Title
Average Rhinoconjunctivitis (RC) DMS During the Peak RS
Description
This DMS endpoint consists of a total of scores for use of RC medications: loratadine syrup or tablets (6 points), olopatadine (6 points), and mometasone (8 points). The score range of the RC DMS is 0-20 points, and a lower DMS means that less medication is used. The method used for analysis of the RC DMS is a zero-inflated log-normal model, which takes the average RC DMS during the peak RS as the response and adjusts for the same terms as in the ANOVA model. The components that contribute to the DMS endpoint are collected in an e-diary completed by the participant/parent/guardian.
Time Frame
The 15-day period during the ragweed season with the highest moving pollen average
Title
Percentage of Participants Reporting Pre-specified Local Application Site Reactions
Description
Pre-specified local application site reactions, irrespective of causality, included AEs related to lip swelling/edema, mouth swelling/edema, palatal swelling/edema, swollen tongue/edema, oropharyngeal swelling/edema, pharyngeal edema/throat tightness, oral pruritus, throat irritation, tongue pruritus, and ear pruritus.
Time Frame
Up to 35 weeks
Title
Percentage of Participants Reporting Anaphylaxis and/or Systemic Allergic Reactions
Description
For the purposes of this study, systemic allergic reactions are allergic reactions that occur away from the site of study drug application (allergic reactions other than local application site reactions). Anaphylaxis is a severe allergic reaction that typically involves more than one body system.
Time Frame
Up to 35 weeks
Title
Percentage of Participants Treated With Epinephrine
Description
Self-injectable epinephrine was provided to each participant/parent/guardian at randomization in countries where it is a regulatory requirement, and was to be available around the time treatment is administered at home. Self-injectable epinephrine was intended for immediate self-administration for an anaphylactic reaction, including symptoms/signs of upper airway obstruction. Instances of treatment with forms of epinephrine other than systemic epinephrine (e.g., inhaled racepinephrine) were counted as use of epinephrine.
Time Frame
Up to 35 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34886880
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.
Results Reference
derived
PubMed Identifier
32926419
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.
Results Reference
derived
PubMed Identifier
32548677
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.
Results Reference
derived
PubMed Identifier
32304832
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.
Results Reference
derived
Learn more about this trial
Efficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008)
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