Moderate to Severe Seasonal Allergic Rhinitis MedDRA version: 20.1 Level: LLT Classification code 10039776 Term: Seasonal allergic rhinitis System Organ Class: 100000004870
Conditions
Interventions
Trade Name: GRAZAX 75,000 SQ-T oral lyophilisate
Product Name: Grazax
Product Code: PHLEUM PRATENSE POLLEN
Pharmaceutical Form: Oral lyophilisate
INN or Proposed INN: Pollen allergen extract from Phle
Sponsors
Division of Allergy, Immunology, and Transplantation; National Institute of Allergy and Infectious Disease
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: 1.Participant must be able to understand and provide informed consent. 2.Adults age 18 to 65 years. 3.A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak symptoms in May, June, or July. 4.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. 5.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. 6.Positive skin prick test response at screening, defined as wheal diameter greater than or equal to 3 mm, to Phleum pratense. 7.Positive specific IgE at screening, defined as greater than or equal to IgE class 2 (0.7 kU/L) against Phleum pratense. 8. A positive response to NAC with Phleum pratense defined as a TNSS greater than or equal to 5 of 12 points. 9.Female participants of childbearing potential, regardless of birth control history, must have a negative serum pregnancy test at screening, must not be breast-feeding or lactating, and are 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); double barrier (i.e., latex condom, diaphragm with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); or bilateral tubal ligation (if no conception post-procedure). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Individuals who meet any of these criteria are not eligible for enrollment as study participants: 1.Inability or unwillingness of a participant to give written informed consent or comply with study protocol. 2.Prebronchodilator forced expiratory volume (FEV1) less than 70% of predicted value at either screening or baseline visit. 3.A clinical history of asthma requiring regular inhaled corticosteroids for > 4 weeks per year outside of the grass pollen season. 4.A clinical history of moderate to severe allergic rhinitis, as defined according to the ARIA classification of rhinitis, caused by either: a.an allergen to which the participant is regularly exposed OR b.tree pollen during tree pollen season treated with regular antihistamine or intranasal corticosteroids. 5.History of emergency visit or hospital admission for asthma in the previous 12 months. 6.History of chronic obstructive pulmonary disease. 7.History of recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment. 8.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 ear pain, pressure, or fullness. 9.History of systemic disease affecting the immune system such as autoimmune diseases, immune complex disease or immunodeficiency. 10.At randomization, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess whether the combination of 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.;Secondary Objective: 1.To assess whether the combination is more effective than SLIT alone in inducing immune tolerance at 1 year after completion of study medication 2.To assess whether the combination is more effective than double-placebo in inducing desensitization to grass pollen at 1 and 2 years whilst on study medication. 3.To assess whether the combination is more effective than SLIT alone in inducing desensitization to grass pollen at 1 and 2 years whilst on study medication. 4.To evaluate the safety and tolerability of the combination of SLIT and dupilumab compared to grass pollen immunotherapy alone. ;Primary end point(s): - NAC (TNSS Area-under-Curve [AUC0-1hr]) ;Timepoint(s) of evaluation of this end point: - 3 years, one year after completion of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical Tolerance Endpoints: 1.Peak nasal inspiratory flow (Delta PNIF AUC0-1hr) 2.TNSS AUC0-1hr Desensitization Endpoints: 3.TNSS AUC0-1hr 4.Delta PNIF AUC0-1hr Safety and Seasonal Symptom Endpoints: 6.Weekly seasonal symptoms (Visual analogue scale [VAS] 0-10 cms) 7.Weekly rhinitis quality of life scores (Juniper mini-RQLQ) 8.Global evaluation scores;Timepoint(s) of evaluation of this end point: Clinical Tolerance Endpoints: - 3 years - 3 years - 1 and 2 years Desensitization Endpoints: - 1 and 2 years - 1 and 2 years Safety and Seasonal Symptom Endpoints: - 3 years - 3 years -3 years | — |
Countries
United Kingdom
Contacts
Public ContactOffice of Regulatory Affairs
Division of Allergy, Immunology, and Transplantation; National Institute of Allergy and Infectious Disease
Outcome results
None listed