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Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 65 Years
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04502966
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Stephen R. Durham, MD
Principal Investigator Affiliation Allergy and Clinical Immunology Section at NHLI,Imperial College London
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIHOtherIndustryIndustryIndustryIndustry
Overall Status Recruiting
Countries United Kingdom
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Allergic Rhinoconjunctivitis, Grass Pollen Allergy
Study Website: View Trial Website
Additional Details

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.

Arms & Interventions

Arms

Experimental: Grazax® +Dupixent®

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

Experimental: Grazax® + Dupixent® Placebo

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

Placebo Comparator: Grazax® Placebo +Dupixent® Placebo

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

Interventions

Biological: - Dupixent®

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

Biological: - Grazax®

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.

Drug: - Dupixent® 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.

Drug: - Grazax® 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.

Contact a Trial Team

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International Sites

Royal Brompton Hospital, London, United Kingdom

Status

Recruiting

Address

Royal Brompton Hospital

London, , SW36HP

Site Contact

Lisa K. Curry

l.curry@imperial.ac.uk

0330 1284407

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