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Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction (GRADUATE)

Primary Purpose

Allergic Rhinoconjunctivitis, Grass Pollen Allergy

Status
Active
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Dupixent®
Grazax®
Dupixent® Placebo
Grazax® Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allergic Rhinoconjunctivitis focused on measuring immunotherapy, nasal allergen challenge (NAC), total nasal symptom score (TNSS)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • A positive response to nasal allergen challenge (NAC) with Phleum pratense defined as a Total Nasal Symptom Score (TNSS) ≥5 points (out of a a maximum possibility 12 points)
  • 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.

Exclusion Criteria:

  • 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
  • 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.

Sites / Locations

  • Royal Brompton Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Grazax® +Dupixent®

Grazax® + Dupixent® Placebo

Grazax® Placebo +Dupixent® Placebo

Arm Description

Participants 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

Participants 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

Participants 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

Outcomes

Primary Outcome Measures

TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
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. 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.

Secondary Outcome Measures

TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and Grazax® + Dupixent® Placebo Treatment Arms
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. 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.
Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr): A Comparison Between Treatment Arms
The following analyses will performed as an assessment of clinical tolerance: Comparison between Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo treatment arms, and Comparison between Grazax® +Dupixent® and the Grazax® + Dupixent® Placebo treatment arms PNIF is defined as the 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 symptoms.
TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
NAC (TNSS Area-under-Curve [AUC 0-1hr]), comparing the TNSS AUC 0-1 hr between the referenced treatment arms: a desensitization to grass pollen outcome measure. 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.
Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
PNIF is defined as the 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 symptoms. This assessment is a desensitization to grass pollen outcome measure.
Frequency, Severity, and Relatedness of Adverse Events (AEs) byTreatment Arm
The number, severity, and relatedness of local and systemic AEs and Serious AEs will be summarized by treatment arm. AEs will be classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0, November 27, 2017). Reference: Safety and Seasonal Symptom outcome measure.
Weekly Seasonal Symptoms Score (Visual analogue scale [VAS] 0-10 cms): A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
A participant-reported (self-administered) seasonal symptoms outcome measure on a Likert scale (0 to 10 cms, 0=No Symptoms, 10=Worst possible symptoms), a quality of life measure reflecting the quality of life impact of rhinitis ("hay fever") symptoms experienced during the span of the "last week."
Weekly Rhinitis Quality of Life Scores Using the Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire: A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
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 "during the last week."
Global Rhinitis Evaluation Scores: A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
Participants are asked, as part of their Year 3 visit, to describe their allergic rhinitis ("hay fever"). This administered set of questions is comprised of 6 questions, focusing on nasal and eye symptoms [0=No symptoms, 3=Severe] and 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). Reference: A clinical tolerance outcome measure.

Full Information

First Posted
August 4, 2020
Last Updated
July 11, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), ALK-Abelló A/S, Regeneron Pharmaceuticals, PPD, Rho Federal Systems Division, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04502966
Brief Title
Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction
Acronym
GRADUATE
Official Title
Grass Pollen Sublingual Tablet Immunotherapy Plus Dupilumab for Induction of Tolerance in Adults With Moderate to Severe Seasonal Allergic Rhinitis (ITN084AD)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 9, 2020 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), ALK-Abelló A/S, Regeneron Pharmaceuticals, PPD, Rho Federal Systems Division, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Rhinoconjunctivitis, Grass Pollen Allergy
Keywords
immunotherapy, nasal allergen challenge (NAC), total nasal symptom score (TNSS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Grazax® +Dupixent®
Arm Type
Experimental
Arm Description
Participants 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
Arm Title
Grazax® + Dupixent® Placebo
Arm Type
Experimental
Arm Description
Participants 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
Arm Title
Grazax® Placebo +Dupixent® Placebo
Arm Type
Placebo Comparator
Arm Description
Participants 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
Intervention Type
Biological
Intervention Name(s)
Dupixent®
Other Intervention Name(s)
dupilumab, monoclonal antibody against the IL-4 receptor
Intervention Description
An initial dose of 600 mg (two 300 mg injections), followed by 300 mg administered every other week (biweekly), by subcutaneous injection.
Intervention Type
Biological
Intervention Name(s)
Grazax®
Other Intervention Name(s)
grass pollen allergen sublingual immunotherapy (SLIT), timothy grass (Phleum pratense) sublingual immunotherapy (SLIT)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Dupixent® Placebo
Other Intervention Name(s)
placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Grazax® Placebo
Other Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
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. 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.
Time Frame
0 to 1 hour of the NAC at Year 3, One Year After Completion of Treatment
Secondary Outcome Measure Information:
Title
TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and Grazax® + Dupixent® Placebo Treatment Arms
Description
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. 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.
Time Frame
0 to 1 hour of the NAC at Year 3, One Year After Completion of Treatment
Title
Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr): A Comparison Between Treatment Arms
Description
The following analyses will performed as an assessment of clinical tolerance: Comparison between Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo treatment arms, and Comparison between Grazax® +Dupixent® and the Grazax® + Dupixent® Placebo treatment arms PNIF is defined as the 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 symptoms.
Time Frame
0 to 1 hour of the NAC at Year 3, One Year After Completion of Treatment
Title
TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
NAC (TNSS Area-under-Curve [AUC 0-1hr]), comparing the TNSS AUC 0-1 hr between the referenced treatment arms: a desensitization to grass pollen outcome measure. 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.
Time Frame
0 to 1 hour of the NAC at Year 1 and Year 2
Title
Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr): A Comparison between the Grazax® +Dupixent® and the Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
PNIF is defined as the 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 symptoms. This assessment is a desensitization to grass pollen outcome measure.
Time Frame
0 to 1 hour of the NAC at Year 1 and Year 2
Title
Frequency, Severity, and Relatedness of Adverse Events (AEs) byTreatment Arm
Description
The number, severity, and relatedness of local and systemic AEs and Serious AEs will be summarized by treatment arm. AEs will be classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0, November 27, 2017). Reference: Safety and Seasonal Symptom outcome measure.
Time Frame
Week 0 to Year 3
Title
Weekly Seasonal Symptoms Score (Visual analogue scale [VAS] 0-10 cms): A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
A participant-reported (self-administered) seasonal symptoms outcome measure on a Likert scale (0 to 10 cms, 0=No Symptoms, 10=Worst possible symptoms), a quality of life measure reflecting the quality of life impact of rhinitis ("hay fever") symptoms experienced during the span of the "last week."
Time Frame
Year 3
Title
Weekly Rhinitis Quality of Life Scores Using the Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire: A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
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 "during the last week."
Time Frame
Year 3
Title
Global Rhinitis Evaluation Scores: A Comparison Between the Grazax® +Dupixent® and Grazax® Placebo +Dupixent® Placebo Treatment Arms
Description
Participants are asked, as part of their Year 3 visit, to describe their allergic rhinitis ("hay fever"). This administered set of questions is comprised of 6 questions, focusing on nasal and eye symptoms [0=No symptoms, 3=Severe] and 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). Reference: A clinical tolerance outcome measure.
Time Frame
Year 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 A positive response to nasal allergen challenge (NAC) with Phleum pratense defined as a Total Nasal Symptom Score (TNSS) ≥5 points (out of a a maximum possibility 12 points) 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. Exclusion Criteria: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen R. Durham, MD
Organizational Affiliation
Allergy and Clinical Immunology Section at NHLI,Imperial College London
Official's Role
Study Chair
Facility Information:
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW36HP
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID)
URL
https://www.niaid.nih.gov/about/dait
Description
Division of Allergy, Immunology, and Transplantation (DAIT)
URL
http://www.immunetolerance.org
Description
Immune Tolerance Network (ITN)

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Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction

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