Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction

NCT04502966 | Completed Phase 2 Results DMC

• 3 other identifiers: DAIT ITN084ADNIAID CRMS ID#: 386292018-003456-20
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 1

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.

Conditions

Allergic Rhinoconjunctivitis; Grass Pollen Allergy

Keywords

immunotherapy; nasal allergen challenge (NAC); total nasal symptom score (TNSS)

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (14)

• 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

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

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

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

• 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

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

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

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

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

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

Study Arms (3)

Grazax® +Dupixent®

EXPERIMENTAL

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

Biological: Dupixent®; Biological: Grazax®

Grazax® + Dupixent® Placebo

EXPERIMENTAL

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

Biological: Grazax®; Drug: Dupixent® Placebo

Grazax® Placebo +Dupixent® Placebo

PLACEBO COMPARATOR

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

Drug: Dupixent® Placebo; Drug: Grazax® Placebo

Interventions

Dupixent® BIOLOGICAL

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

Also known as: dupilumab, monoclonal antibody against the IL-4 receptor

Grazax® +Dupixent®

Grazax® BIOLOGICAL

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.

Also known as: grass pollen allergen sublingual immunotherapy (SLIT), timothy grass (Phleum pratense) sublingual immunotherapy (SLIT)

Grazax® + Dupixent® Placebo; Grazax® +Dupixent®

Dupixent® Placebo DRUG

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.

Also known as: placebo

Grazax® + Dupixent® Placebo; Grazax® Placebo +Dupixent® Placebo

Grazax® Placebo DRUG

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.

Also known as: placebo

Grazax® Placebo +Dupixent® Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator
• ALK-Abelló A/S: collaborator
• Regeneron Pharmaceuticals: collaborator
• PPD Development, LP: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (1)

Royal Brompton Hospital

London, SW36HP, United Kingdom

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Immune Tolerance Network (ITN)

MeSH Terms

Interventions

dupilumab; Grazax; Sublingual Immunotherapy

Intervention Hierarchy (Ancestors)

Desensitization, Immunologic; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

3015947669

Study Officials

• Stephen R. Durham, MD

  Allergy and Clinical Immunology Section at NHLI,Imperial College London

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 6, 2020
• Study Start: November 5, 2020
• Primary Completion: February 20, 2025
• Study Completion: February 20, 2025
• Last Updated: April 27, 2026
• Results First Posted: April 27, 2026

Record last verified: 2026-04

Locations

GB (1)