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Rhinitis, Allergic, SeasonalPhase 3NCT02478398

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

A Phase 3 study testing Short ragweed pollen allergen extract, Self-injectable epinephrine and Albuterol/Salbutamol in people with Rhinitis, Allergic, Seasonal, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 to 17 years
Conditions the study is for
Rhinitis, Allergic, Seasonal
What is being tested?
Short ragweed pollen allergen extract, Self-injectable epinephrine and Albuterol/Salbutamol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,025 participants
Where
No sites listed yet
Study dates
20 Jul 2015to 19 Nov 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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
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  • 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

About this study

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

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).

Being tested
Short ragweed pollen allergen extract, Placebo, Self-injectable epinephrine, Albuterol/Salbutamol, Loratadine
Medical subject headings
Rhinitis, Allergic, Seasonal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Short ragweed pollen allergen extractBiological

    Also called RAGWITEK™, MK-3641

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

  • PlaceboBiological

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

  • Self-injectable epinephrineDrug

    Also called EpiPen

    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/SalbutamolDrug

    Also called ProAir HFA, Proventil HFA, Ventolin HFA

    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

  • LoratadineDrug

    Also called Claritin

    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

  • OlopatadineDrug

    Also called Patanol

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

  • Mometasone furoate monohydrateDrug

    Also called Nasonex

    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

Study groups in NCT02478398
Study groupRoleWhat they receive
Short ragweed pollen allergen extractExperimentalParticipants 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.
Receives: Biological: Short ragweed pollen allergen extract; Drug: Self-injectable epinephrine; Drug: Albuterol/Salbutamol; Drug: Loratadine; Drug: Olopatadine; Drug: Mometasone furoate monohydrate
PlaceboPlacebo comparatorParticipants 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.
Receives: Biological: Placebo; Drug: Self-injectable epinephrine; Drug: Albuterol/Salbutamol; Drug: Loratadine; Drug: Olopatadine; Drug: Mometasone furoate monohydrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)

  1. 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.

    Measured: Up to 13 weeks

  2. 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.

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

  3. 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.

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

  4. 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.

    Measured: Up to 35 weeks

  5. 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.

    Measured: Up to 35 weeks

  6. 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.

    Measured: Up to 35 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2015 (estimated)
  2. Study start20 Jul 2015
  3. Primary completion9 Nov 2018
  4. Study completion19 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
1,025 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02478398
Sponsor's protocol ID
3641-008
Other IDs
2014-004341-27, MK-3641-008, 2014
Status last verified
Aug 2019
First submitted
22 Jun 2015
Last updated
6 Sep 2019
Data monitoring committee
Yes
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 34886880

  • 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.

    PubMed 32926419

  • 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.

    PubMed 32548677

  • 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.

    PubMed 32304832

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Short ragweed pollen allergen extract, Self-injectable epinephrine and Albuterol/Salbutamol in people with Rhinitis, Allergic, Seasonal, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Combined Score (TCS) During the Peak Ragweed Season (RS) (time frame: The 15-day period during the ragweed season with the highest moving pollen average). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02478398, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.

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