Patients with grass pollen related allergic rhinitis/rhino-conjunctivitis (with or without well controlled asthma).
Conditions
Interventions
Product Name: SULGEN Spray Phleum pratense
Pharmaceutical Form: Sublingual spray, solution
INN or Proposed INN: PHLEUM PRATENSE POLLEN EXTRACT
Other descriptive name: PHLEUM PRATENSE POLLEN
Concentrat
Sponsors
ROXALL Medicina España S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: • Patients who signed and dated the patients' informed consent form obtained prior to any study specific examination. • Female or male patients between 18 and 65 years of age, at the time of signing the informed consent form • Patients with moderate-to-severe allergic rhinitis / rhino-conjunctivitis due to grass pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline. • Patients with or without well controlled mild-to-moderate asthma according to GINA guideline (Global Initiative for Asthma, 2017). • Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value for patients with a history of asthma. • Sensitization to Phleum pratense, verified by: a) positive skin prick test (wheal diameter = 3 mm and negative control =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Previous immunotherapy with allergen extract of grass pollen according to the Grass and cereal pollen (Pooideae) homologous group, as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831) within the last 5 years • Patients with co-sensitizations to any perennial or seasonal allergen with clinical manifestations or co-allergies, whose allergic symptoms interfere with the conduct of the study (e. g. with the tNPT) • Simultaneous participation in other clinical trials • Simultaneous specific immunotherapy with other allergens • Participation in a clinical trial in the last three months before enrolment • Asthmatic patients with forced expiratory volume (FEV1) = 70 % of predicted normal value • Partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2017) • Severe acute or chronic inflammatory or infectious diseases • Inflammations or lesions within the oral cavity (e. g. gingivitis) as well as gastroenteritis at randomization • Diseases of the immune system such as autoimmune and immune deficiencies (with exception to well controlled Hashimoto thyroiditis and type-1 diabetes mellitus) • Immunosuppressive therapy within 3 month prior screening • Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function • Hypersensitivity to excipients of the IMP • Any severe or unstable lung disease (e. g. active tuberculosis, cystic fibrosis, COPD) • Chronic or severe acute diseases of nose or eyes • Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis) • Therapy with immunoglobulins • Completed or ongoing treatment with anti-IgE-antibody • Malignancy within the previous 5 years • Alcohol, drug, or medication abuse within the past year and/or during the study • Use of non-allowed medication (see section 8.3.1) • Contraindications for SPT • Contraindication for NPT • Patients with PNIF decrease = 20 % during tNPT after application of control solution at V0 • Relationship or dependence with the sponsor and/or investigator • Legal incapacity • Patients who are jurisdictional or governmentally institutionalized • Serious systemic reactions to allergen-specific immunotherapy in the past • Active chronic urticaria • Active severe atopic eczema • Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with child-bearing potential or a positive pregnancy test at screening • Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizers or psychactive drugs (including tricyclic antidepressants) • Risk of non-compliance by the patient with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this trial is to establish the optimal dose of SULGEN® Spray Phleum pratense in terms of benefit-risk balance. Primary endpoint: To assess the clinical efficacy of four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo. The primary efficacy endpoint is defined as percentage of patients with an increased dosing step needed to provoke a positive response in the titrated nasal provocation test (tNPT) post-treatment compared with pre-treatment (i. e. any improvement) in each of the five study groups. This is based on the change of the response to tNPT with incremental concentrations of an allergen extract of Phleum pratense from baseline to end of treatment.;Secondary Objective: Secondary efficacy endpoint: To assess the clinical efficacy of four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo by the changes in the number of dosing steps (pre-post difference) needed to provoke a positive response in the tNPT Secondary safety endpoint: To analyse the safety and tolerability of four different doses of SULGEN® Spray Phleum pratense by number of treatment-emergent adverse drug reactions and number of patients affected in each study group. Exploratory endpoints 1. To assess the immunogenicity by changes in the serum specific immunoglobulin levels (specific IgG4 against Phleum pratense) from baseline to end of treatment. 2. To assess the clinical global evaluation of the treatment with four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo (rated by the patient and investigator on a 4-point rating score each at the end of the treatment).;Primary end point(s): The primary endpoint of the study is defined as percentage of patients with an increased dosing step needed to provoke a positive response in tNPT (i. e. a higher tNPT threshold) at last visit (FV) in comparison to tNPT at V0. The optimal treatment (dose leve | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy parameter: The secondary endpoint is defined as the change in the number of dosing steps (pre-post difference) needed to provoke a positive response in the tNPT. Comparisons will be performed pairwise between the five study groups and within each study group. Secondary safety endpoint: To analyse the safety and tolerability of four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo by number of treatment-emergent adverse drug reactions and number of patients affected in each study group. Exploratory endpoints 1. To assess the immunogenicity of four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo by changes in the serum specific immunoglobulin levels (specific IgG4 against Phleum pratense) from baseline to end of treatment. 2. To assess the clinical global evaluation of the treatment with four different doses of SULGEN® Spray Phleum pratense compared between each other and to placebo (rated by the patient and investigator on a 4-point rating score each at the end of the treatment).;Timepoint(s) of evaluation of this end point: 7,5 months | — |
Countries
Spain
Contacts
Public ContactLeire Begoña
ROXALL Medicina España S.A.
Outcome results
None listed