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Allergic RhinoconjunctivitisPhase 2GRADUATENCT04502966

Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction

A Phase 2 study testing Dupixent® and Grazax® in people with Allergic Rhinoconjunctivitis and Grass Pollen Allergy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United Kingdom.

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 primary objective of this study is to assess whether the combination of grass allergen sublingual immunotherapy (SLIT) and dupilumab for 2 years is more effective than double placebo in suppressing the nasal allergen challenge (NAC) response to grass pollen at 1 year after completion of study medication. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Dupixent® and Grazax®
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
199 participants
Where
1 siteUnited Kingdom
Study dates
5 Nov 2020to 20 Feb 2025
Phase
Phase 2
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant must be able to understand and provide informed consent
  • A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years, with peak symptoms in May, June, or July
  • A clinical history of moderate to severe rhinoconjunctivitis symptoms for at least 2 years, interfering with usual daily activities or with sleep as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis
  • A clinical history of inadequately controlled rhinoconjunctivitis symptoms, despite treatment with antihistamines and/or nasal corticosteroids during the grass pollen season, for at least 2 years
  • Positive skin prick test response at screening, defined as wheal diameter ≥3 mm to Phleum pratense
  • Positive specific immunoglobulin E (IgE) at screening, defined as IgE class 2 (e.g., ≥ 0.7 kilounits per liter [kU/L]) against Phleum pratense
Show all 14Show fewer
  • A woman of childbearing potential (WOCBP), regardless of birth control history, must:
  • have a negative serum pregnancy test at screening,
  • not be breast-feeding or lactating, and ---is required to consistently use one of the following highly effective methods of contraception throughout the study:
  • hormonal (e.g. oral, transdermal, intravaginal, implant, or injection),
  • intrauterine device (IUD) or system (IUS),
  • vasectomized partner,
  • bilateral tubal occlusion, or
  • sexual abstinence.

Who cannot join

  • Inability or unwillingness of the Subject to give written informed consent or to comply with study protocol requirements
  • Prebronchodilator forced expiratory volume (FEV1) <70% of predicted value at either Screening Visit or Baseline (Visit 0) Visit
  • A clinical history of asthma requiring regular inhaled corticosteroids for >4 weeks per year, outside of the grass pollen season
  • A clinical history of moderate to severe allergic rhinitis, as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis, caused by either:
  • An allergen to which the Subject is regularly exposed, or
  • Tree pollen during tree pollen season, treated with regular antihistamine or intranasal corticosteroids
Show all 46Show fewer
  • History of emergency visit or hospital admission for asthma in the previous 12 months
  • History of chronic obstructive pulmonary disease
  • History of recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment
  • History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks, that includes 2 or more major factors or 1 major factor and 2 minor factors.
  • Major factors are defined as:
  • Facial pain or pressure,
  • Nasal obstruction or blockage,
  • Nasal discharge or purulence or discolored postnasal discharge,
  • Purulence in nasal cavity, or
  • Impaired or loss of smell.
  • Minor factors are defined as:
  • Headache,
  • Fever,
  • Halitosis,
  • Fatigue,
  • Dental pain,
  • Cough, and/or
  • Ear pain, pressure, or fullness.
  • History of systemic disease affecting the immune system, such as autoimmune diseases, immune complex disease or immunodeficiency
  • At randomization: Current symptoms of, or treatment for:
  • Upper respiratory tract infection,
  • Acute sinusitis,
  • Acute otitis media, or
  • Other relevant infectious process ---Note: 1.) Serous otitis media is not an exclusion criterion and 2.) Participants may be re-evaluated for eligibility after symptoms resolve.
  • A past history of any malignant disease in the previous 5 years
  • Any tobacco smoking within the last 6 months, or a history of greater than or equal to 10 pack years of cigarette use.
  • Any vaping or electronic cigarette use within the last 6 months
  • Previous immunotherapy with grass pollen allergen within the previous 5 years
  • Previous treatment by dupilumab (Dupixent®)
  • Previous Grade 4 anaphylaxis (World Allergy Organization grading criteria), due to any cause
  • History of anti-IgE, anti-IL-5, anti-IL-5 receptor, anti-IL-4/IL-13 receptor, or other monoclonal antibody treatment
  • Use of tricyclic antidepressants or monoamine oxidase inhibitors
  • Ongoing systemic immunosuppressive treatment
  • History of intolerance to the study therapy, rescue medications, or their excipients
  • For women of childbearing age a positive serum or urine pregnancy test with sensitivity of less than 50 milli-international units per milliliter [mIU/ml] within 72 hours before the scheduled start of study therapy
  • The use of any investigational drug within 30 days of the Screening Visit
  • The presence of any medical condition that the investigator deems incompatible with participation in the trial
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
  • Eosinophilic esophagitis or a diagnosis of any hypereosinophilic syndrome, and/or
  • Administration of live attenuated vaccines within four weeks of dupilumab or dupilumab placebo injections, before the first injection and throughout the treatment period.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Royal Brompton Hospital

    London, SW36HP

Other trials in United Kingdom

About this study

Official title: Grass Pollen Sublingual Tablet Immunotherapy Plus Dupilumab for Induction of Tolerance in Adults With Moderate to Severe Seasonal Allergic Rhinitis (ITN084AD)

The primary objective of this study is to assess whether the combination of grass allergen sublingual immunotherapy (SLIT) and dupilumab for 2 years is more effective than double placebo in suppressing the nasal allergen challenge (NAC) response to grass pollen at 1 year after completion of study medication.

Read the detailed description

This is a double-blind (masked) placebo-controlled trial in adults (N=108 subjects will be enrolled) with moderate to severe seasonal allergic rhinitis and allergic sensitization to grass pollen. Eligible participants who demonstrate a positive response defined by a Total Nasal Symptom Score [TNSS] ≥ 5 (Scale 0-12 in response to a Nasal Allergen Challenge [NAC] with grass pollen extract), will be randomized to one of the following 3 groups in a 1:1:1 ratio:

  • Grass allergen sublingual immunotherapy (SLIT) + dupilumab (n=36)
  • Grass allergen SLIT +dupilumab placebo (n=36)
  • Grass allergen SLIT placebo + dupilumab placebo (n=36)

Grazax® is a sublingual grass allergen immunotherapy product approved for clinical use in the United Kingdom and will be used as SLIT in this study. Grazax (and its matching placebo) will be self-administered daily by participants for a duration of two years.

Dupixent®is the brand name for dupilumab and is a monoclonal antibody against the interleukin 4 (IL-4) receptor. Dupilumab (and its matching placebo) will be administered every two weeks by subcutaneous injection through for a duration of two years, administered by study personnel. The treatment phase of two years will be followed by an observation phase of 1 year.

Being tested
Dupixent®, Grazax®, Dupixent® Placebo, Grazax® Placebo
Keywords
immunotherapy, nasal allergen challenge (NAC), total nasal symptom score (TNSS)

What participants receive

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

  • Dupixent®Biological

    Also called dupilumab, monoclonal antibody against the IL-4 receptor

    An initial dose of 600 mg (two 300 mg injections), followed by 300 mg administered every other week (biweekly), by subcutaneous injection.

  • Grazax®Biological

    Also called grass pollen allergen sublingual immunotherapy (SLIT), timothy grass (Phleum pratense) sublingual immunotherapy (SLIT)

    One Grazax® tablet daily, by sublingual administration.

    Grazax® is formulated as a freeze-dried oral lyophilisate/orally disintegrating tablet for oromucosal use. The active pharmaceutical ingredient is a standardized allergen extract derived from extraction and purification of grass pollen from timothy grass (Phleum pratense). The biological activity of the allergen is expressed in Standardized Quality Tablet units (SQ-T) units. The Grazax® dosage is one oral lyophilisate (75,000 Standardized Quality Tablet units (SQ-T) or approximately 2800 Bioequivalent allergy units (BAU), a measure of Phleum pratense SQ total biological potency defined by the FDA.

  • Dupixent® PlaceboDrug

    Also called placebo

    Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose followed by a single injection administered every other week.

    Dupixent® placebo is a subcutaneous injection whose composition is identical to the active Dupixent®, with the exception of the active pharmaceutical ingredient.

  • Grazax® PlaceboDrug

    Also called placebo

    One tablet of Placebo (for Grazax®) daily, by sublingual administration.

    Grazax® placebo is a tablet whose composition is identical to the active Grazax® tablet with the only exception being exclusion of the active pharmaceutical ingredient, Phleum pratense Standardized Quality Tablet (SQ-T) units.

Study groups in NCT04502966
Study groupRoleWhat they receive
Grazax® +Dupixent®ExperimentalParticipants randomized to this assignment will receive the following during the initial 2-year period of the trial: * Once daily tablet of Grazax® sublingual immunotherapy and * Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
Receives: Biological: Dupixent®; Biological: Grazax®
Grazax® + Dupixent® PlaceboExperimentalParticipants randomized to this assignment will receive the following during the initial 2-year period of the trial: * Once daily tablet of Grazax® sublingual immunotherapy and * Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
Receives: Biological: Grazax®; Drug: Dupixent® Placebo
Grazax® Placebo +Dupixent® PlaceboPlacebo comparatorParticipants randomized to this assignment will receive the following during the initial 2-year period of the trial: * Once daily tablet of placebo for Grazax® sublingual immunotherapy and * Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
Receives: Drug: Dupixent® Placebo; Drug: Grazax® Placebo

What is being measured

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

  1. TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Year 3

    NAC (TNSS Area-under-Curve [AUC 0-1hr]), comparing the TNSS AUC 0-1 hr between the referenced treatment arms: a clinical tolerance outcome measure at Year 3, one year after completion of treatment.

    The Total Nasal Symptom Score (TNSS) is a participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching and sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score is calculated as the sum of the response for all 4 individual nasal symptom scores and can range from a minimum score of 0 to a maximum score of 12: a higher score indicates more severe symptoms.

    The primary treatment comparison is between SLIT/Dupilumab and Double-Placebo.

    Measured: 0 to 1 hour of the NAC at Year 3 (One Year After Completion of Treatment)

Secondary outcomes (14)

  1. TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1 and 2

    NAC (TNSS Area-under-Curve [AUC 0-1hr]), comparing the referenced treatment arms at years 1 and 2 while on study treatment for clinical desensitization.

    The Total Nasal Symptom Score (TNSS) is a participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching and sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score is calculated as the sum of the response for all 4 individual nasal symptom scores and can range from a minimum score of 0 to a maximum score of 12: a higher score indicates more severe symptoms.

    The following treatment comparisons are of secondary outcome interest:

    • Comparison between SLIT/Dupilumab and Double-Placebo
    • Comparison between SLIT/Dupilumab versus SLIT/Dupilumab Placebo

    Both treatment comparisons are key secondary endpoints at Year 2 and therefore multiplicity adjustments are considered; however, at Year 1 the same comparisons are not adjusted for multiplicity.

    Measured: 0 to 1 hour of the NAC at Years 1 and 2

  2. Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr) at Years 1, 2, and 3

    PNIF is defined as the maximum effort speed of inspiration of air in Liters per minute when breathing into the lungs through the nose. Lower scores indicate less ability to breathe air into the lungs due to more severe nasal congestion.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however, at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: 0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  3. TNSS Peak (Maximum) Value Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1, 2, and 3

    The NAC Total Nasal Symptom Score (TNSS) is a participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching and sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score is calculated as the sum of the response for all 4 individual nasal symptom scores and can range from a minimum score of 0 to a maximum score of 12: a higher score indicates more severe symptoms.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: 0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  4. Size of Early Intradermal Skin Test Response at Years 1, 2, and 3

    An intradermal skin test will be performed in duplicate (left and right arm) using Timothy grass pollen, with an early phase read-out after 15 minutes (with a +/- 3 minute window). A 10 BU test concentration will be used. The average of left and right arm wheal sizes will be used for analysis. A higher wheal size indicates a more severe reaction.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  5. Size of Late Intradermal Skin Test Response at Years 1, 2, and 3

    An intradermal skin test will be performed in duplicate (left and right arm) using Timothy grass pollen, with a late phase read-out after 6.5 hours (with a +/- 30 minute window) post initial injection. A 10 BU test concentration will be used. The average of left and right arm induration sizes will be used for analysis. A higher induration indicates a more severe reaction.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however, at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  6. Size of Skin Prick Test Endpoint Titration Response as Defined by the Provocative Concentration at 5mm (PC5) at Years 1, 2, and 3

    A skin prick test endpoint titration response assessment will be performed in left and right arms using increasing concentrations of Timothy grass pollen (0.001 to 10 HEP U/mL). The average of left and right arm wheal sizes will be analyzed. The PC5 is defined as the minimum concentration (on base-10 log scale) for which an average wheal size is ≥5mm, based on linear interpolation. A smaller PC5 indicates a more severe reaction. Geometric means were back-transformed to original HEP U/mL scale from log10 values.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however, at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  7. Weekly Seasonal Combined Symptom Medication Score (CSMS) at Years 1, 2, and 3 (In Season Estimates)

    A participant-reported seasonal symptoms outcome calculated as average of: a) weekly Visual Analogue Scale (VAS) score and b) weekly medication score (WMS), each assessed for the 7 days prior to the assessment. VAS (0=No Symptoms, 10=Worst possible symptoms) and WMS (0 = medications not used this week, 10 = medications on 5 or more days this week). Weekly Seasonal CSMS ranges from 0-10, with 10 being the highest severity. The average score per participant was calculated across the "in-season" weeks per year.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    This treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  8. Weekly Seasonal Visual Analogue Scale (VAS) 0-10cm Score at Years 1, 2, and 3 (In Season Estimates)

    A participant-reported (self-administered) seasonal symptoms outcome measure on a Likert scale (0 to 10 cm, 0=No Symptoms, 10=Worst possible symptoms), a quality of life measure reflecting the impact of rhinitis ("hay fever") symptoms experienced during the 7 days prior to the assessment. The average score per participant was calculated across the "in-season" weeks per year.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo According to the SAP, no comparisons at any year are adjusted for multiplicity for this outcome.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  9. Weekly Seasonal Medication Score (WMS) at Years 1, 2, and 3 (In Season Estimates)

    A participant-reported (self-administered) seasonal symptoms medications score based on the use of antihistamines (oral and/or eyedrop) and intranasal corticosteroids, assessed for the 7 days prior to the assessment. The WMS has a score ranging from 0 to 10 (0 = medications not used this week, 10 = medications on 5 or more days this week). The average score per participant was calculated across the "in-season" weeks per year.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo According to the SAP, no comparisons at any year are adjusted for multiplicity for this outcome.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  10. Weekly Rhinitis Quality of Life Score Using the Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) at Years 1, 2, and 3 (In Season Estimates)

    The Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) is a participant-reported (self-administered) questionnaire that consists of 14 questions grouped into 5 domains. Each question is scored on a scale of 0 (not troubled with symptoms) to 6 (extremely troubled with symptoms) and describes nose/eye symptoms experienced for the 7 days prior to the assessment. A total score was calculated as average of all questions. The average total score per participant was calculated across the "in-season" weeks per year.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  11. Modified Rhinitis Symptom Utility Index (MRSUI) Questionnaire Measured In-Season at Years 1, 2, and 3

    The Modified Rhinitis Symptom Utility Index (MRSUI) questionnaire consists of 10 questions regarding symptoms experienced during the prior 2 weeks from the nose, eyes, and throat, specifically how frequently the symptoms occurred and how bothersome they were. The total MRSUI score will be calculated as the sum of the numeric responses to all 10 questions. The total MRSUI score ranges from 0-25, with 25 being the worst outcome.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  12. Global Evaluation Questionnaire Number 1 at Years 1, 2, and 3

    Participants are asked to describe their allergic rhinitis ("hay fever"). This administered questionnaire is comprised of 6 questions, focusing on nasal and eye symptoms [0=No symptoms, 3=Severe]. The total Global Evaluation No. 1 score will be calculated as the total sum of the numeric responses to all 6 questions. Higher scores indicate a worse outcome/severity, where the minimum score is 0 and maximum score is 18.

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however, at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  13. Global Evaluation Questionnaire Number 2 at Years 1, 2, and 3

    For the Global Evaluation No. 2 questionnaire, participants are asked a single question regarding the change in current rhinitis/hay fever compared to the years prior to initiating study treatment (Much better: +3, Much worse: -3).

    The following treatment comparison is of secondary outcome interest, where Year 3 is a clinical tolerance outcome measure, and Years 1 and 2 are clinical desensitization outcome measures:

    • Comparison between SLIT/Dupilumab and Double-Placebo

    According to the SAP, this treatment comparison at Year 3 is a key secondary endpoint and therefore a multiplicity adjustment is considered; however at Years 1 and 2 the comparisons are not adjusted for multiplicity.

    Measured: Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment)

  14. Frequency, Severity, and Relatedness of Treatment-Emergent Adverse Events (AEs) by Treatment Arm

    The number and percentage of participants with at least one treatment-emergent AE in the following categories will be summarized by treatment arm:

    1. any AE related to any study drug
    2. any severe (Grade 3 or higher) AE

    Only treatment-emergent AEs will be summarized. All AEs, including local, systemic, and serious AEs will be considered. For grading severity, the protocol-specified grading criteria will be used which depends on the type of AE:

    • Grading Table for Local Reactions to SLIT (Grades 1-4)
    • Grading Table for Local Reactions to Allergen Skin Testing (Grades 1-3)
    • Grading Table for NAC Procedure for Local Reactions (Grades 1-4)
    • WAO Subcutaneous Immunotherapy Systemic Reaction Grading System (Grades 1-5) for any immediate (0-1hr) systemic allergic reaction
    • National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 (November 27, 2017; Grades 1-5) for all remaining AEs.

    Measured: Start of study treatment until completion of study participation at year 3, or until 30 days after prematurely withdrawing from the study

Timeline

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

  1. First posted6 Aug 2020
  2. Study start5 Nov 2020
  3. Primary completion20 Feb 2025
  4. Study completion20 Feb 2025

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
199 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04502966
Sponsor's protocol ID
DAIT ITN084AD
Other IDs
NIAID CRMS ID#: 38629, 2018-003456-20, 2018
Acronym
GRADUATE
Status last verified
Apr 2026
First submitted
4 Aug 2020
Last updated
27 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dupixent® and Grazax® in people with Allergic Rhinoconjunctivitis and Grass Pollen Allergy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United Kingdom.

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 14 inclusion and 46 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 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 27 Apr 2026). 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?

TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Year 3 (time frame: 0 to 1 hour of the NAC at Year 3 (One Year After Completion of Treatment)). 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 NCT04502966.

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 27 Apr 2026.

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