E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rhinoconjunctivitis due to ragweed allergy |
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E.1.1.1 | Medical condition in easily understood language |
Ragweed allergic rhinitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of MK-3641 sublingual immunotherapy tablet (12 Amb a 1-U) versus placebo in the treatment of children 5 to 17 years of age with ragweed-induced rhinoconjunctivitis, with or without asthma, based on the Total Combined Score (TCS) [sum of rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS)] averaged over the peak ragweed season (RS) |
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E.2.2 | Secondary objectives of the trial |
To compare the following between the MK-3641 (12 Amb a 1 U) and placebo groups:
1.Average TCS during the entire RS ;
2.Average rhinoconjunctivitis DSS during the peak RS;
3.Average rhinoconjunctivitis DMS during the peak RS.
To assess the overall safety of MK-3641 (12 Amb a 1 U) in children 5 to 17 years of age with ragweed-induced rhinoconjunctivitis, with or without asthma. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood and/or saliva) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal inclusion criteria |
In order to be eligible for participation in this trial, the subject must:
1.Have a legal representative who provides written informed consent for the trial on the subject’s behalf. The legal representative may also provide consent for Future Biomedical Research on the subject’s behalf. The subject, depending on their age and ability to understand the nature and intent of the study, must also assent to participate in the study main trial and to Future Biomedical Research.
2.Be ≥4 to ≤17 years of age on the day informed consent is obtained, however, the subject must be ≥5 years old at the Randomization Visit. The subject may be of either gender and any race/ethnicity.
3.Have 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.
4.Have a positive skin prick test response to Ambrosia artemisiifolia at the Screening Visit.
5.Have a specific IgE against Ambrosia artemisiifolia ≥ IgE Class 2 (0.7 kU/L) at the Screening Visit.
6.Have a forced expiratory volume in 1 second (FEV1) ≥80% of predicted value at the Screening and Randomization Visits.
Note: A subject who is ≤7 years old and cannot perform reproducible FEV1 maneuvers, despite coaching, does not need to meet this criterion.
7.Be able to read, understand, and complete the questionnaires and diaries (or can have help from the parent/guardian).
8.If female, agree to remain abstinent or use (or have their partner use) an acceptable method of birth control.
Refer to protocol for complete list of inclusion criteria. |
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E.4 | Principal exclusion criteria |
The subject must be excluded from participating in the trial if the subject:
1.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.
2.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.
3.Has any nasal condition that could confound the efficacy or safety assessments (e.g., nasal polyposis).
4.Has asthma requiring high daily doses of inhaled corticosteroids within the 6 months prior to the Screening Visit.
5.Is one of the following:
• >7 years old and cannot perform reproducible FEV1 maneuvers despite coaching;
• ≤7 years old who 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.
6.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.
7.Has a history of anaphylaxis with cardiorespiratory symptoms with prior immunotherapy, unknown cause, or inhalant allergen.
8.Has a diagnosis of eosinophilic esophagitis.
9.Has a history of chronic urticaria and/or chronic angioedema.
10.Has a clinical history of chronic sinusitis during the 2 years prior to the Screening or Randomization Visits.
11.Has current severe atopic dermatitis.
12.Has a history of allergy, hypersensitivity, or intolerance to the ingredients of the investigational medicinal products (except for Ambrosia artemisiifolia), rescue medications, or self-injectable epinephrine.
13.Has previously received MK-3641.
14.Is unable to meet medication washout requirements.
Refer to protocol for complete list of exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study, the Total Combined Score (TCS), is a combination of (sum of) the rhinoconjunctivitis daily symptom score (DSS) and the rhinoconjunctivitis daily medication score (DMS) averaged over the peak ragweed season. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Average Total Combined Score (TCS) during the Entire Ragweed Season (RS)
•Average rhinoconjunctivitis Daily Symptom Score (DSS) during the Peak Ragweed Season
•Average rhinoconjunctivitis Daily Medication Score (DMS) during the Peak Ragweed Season |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Entire Ragweed Season
•Peak Ragweed Season |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Russian Federation |
Serbia |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |