Phase II Dose-Finding Study of Sublingual Phleum pratense Extract in Adults with Grass Pollen‑Induced Allergic Rhinitis
- Trial ID
- 2025-522730-31-00
- Protocol
- APISLIT-DD-G-2025-01
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the optimal dose of Phleum pratense allergen extract for sublingual immunotherapy in patients with allergic rhinitis, ensuring therapeutic efficacy is achieved without compromising safety. 9
The secondary objectives include:
- Assessment of rescue medication use in relation to the investigational product or placebo.
- Evaluation of the safety profile by monitoring local and systemic adverse reactions.
- Monitoring the evolution of specific IgE to Phleum pratense and major allergens.
- Measurement of IgG4 levels for Phleum pratense from baseline to the end of the study.
- Evaluation of changes in skin prick test reactivity.
- Independent analysis of variables associated with the nasal provocation test results.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of patients aged between 12 and 50 years, including both males and females. Participants are diagnosed with allergic rhinitis, which may present with or without rhinoconjunctivitis or associated asthma. For individuals with asthma, required pulmonary function parameters include a forced expiratory volume in one second (FEV1) greater than 70% of the predicted value and a forced vital capacity (FVC) greater than 80% of the predicted value. Selection is based on a positive skin prick test to Phleum pratense or a homologous grass allergen, showing a mean wheal diameter at least 5 mm greater than the negative control. Additionally, a specific IgE level of at least 0.70 kU/L for the allergen and a positive nasal provocation test at a maximum concentration of 1/10 are required. Inclusion excludes individuals who have received specific immunotherapy with Phleum pratense or related pollen within the previous 5 years. Women of childbearing potential must confirm the absence of pregnancy via a negative urine pregnancy test at study entry and at the conclusion of treatment.
Plans and Procedures
This Phase II, randomized, dose determination clinical trial aims to identify the most effective dose of Phleum pratense allergen extract for sublingual immunotherapy. The study focuses on patients diagnosed with allergic rhinitis caused by grass pollen allergy. The research methodology involves comparing different doses of the test product, administered as a sublingual spray, against a placebo consisting of sodium chloride. Participants will undergo a screening visit to confirm eligibility through criteria such as skin prick test results, specific IgE determination, and a positive nasal provocation test. The primary endpoint is the individual response to the nasal provocation test, measured via Nasal Inspiratory Peak Flow and a clinical symptom scoring scale. Secondary endpoints include the assessment of adverse reactions, use of rescue medication, and changes in serum markers such as IgG4. The trial includes follow-up procedures and an end-of-study visit to evaluate clinical variables and laboratory determinations. The total duration of the study period is estimated between September 2026 and April 2027.
Treatment
The experimental medication consists of three doses of Phleum pratense administered via sublingual route. The test products are provided as a sublingual spray or solution in doses of 0.2 ml. The investigated concentrations are 1000 TBU/ml, 3000 TBU/ml, and 6000 TBU/ml.
The placebo is composed of sodium chloride. It is administered as a 0.2 ml sublingual spray or solution.
An auxiliary treatment is utilized consisting of Phleum pratense administered via nasal use. This powder for solution for inhalation is administered at a dose of 0.8 ml for a nasal provocation test.
Efficacy
The efficacy of the sublingual immunotherapy will be evaluated through several parameters. The primary endpoint is the individual response to a nasal provocation test. This assessment involves measuring the change in nasal inspiratory peak flow using a portable nasal inspiratory flow meter. A positive response is defined as a reduction in nasal inspiratory peak flow of 40% or greater. Additionally, a clinical assessment will be conducted based on the total sum of symptoms using a scoring scale with a maximum of 13 points.
Secondary endpoints include the independent analysis of each clinical variable within the symptom scoring scale. Laboratory assessments will be performed to determine serum markers at baseline and at the end of the study, specifically targeting specific IgE to Phleum pratense and major allergens rPhl p1 and rPhl p5b, as well as Phleum pratense IgG4. A skin prick test for Phleum pratense will also be conducted at baseline and at the end of the study for comparative analysis. The use of rescue medication throughout the study in relation to the investigational product or placebo will be monitored.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age between 12 and 50 years
- Diagnosis of allergic rhinitis with/without conjunctivitis, with/without associated asthma. In patients with associated asthma at the time of recruitment, lung function must be FEV1 > 70% of predicted and FVC > 80% of predicted
- Positive skin prick test to *Phleum pratense* using the extracts supplied by the Sponsor.
- Centrally performed determination of Phleum pratense-specific IgE ≥ 0.70 kU/L.
- Positive nasal provocation test result obtained with a maximum concentration of 1/10
- Signed informed consent to participate in the study
- In women of childbearing potential (considered fertile from menarche to post-menopause unless sterilized due to hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), certainty of not being pregnant at study entry, which will be confirmed by a negative urine pregnancy test. In addition, a new pregnancy test must be performed at the end of treatment to confirm absence of pregnancy
- No prior specific immunotherapy with Phleum pratense extracts or any related pollen within the last 5 years, and not receiving concomitant specific immunotherapy with Phleum pratense or any other allergen during the study period
Exclusion Criteria
- Sensitization (skin prick test and/or specific IgE) to perennial allergens (animal dander, environmental fungi, storage mites, or any other allergenic source depending on each participating site’s geographic location) that may interfere with the patient’s clinical evolution during follow-up. Tests and determinations performed within a maximum of 6 months prior to the inclusion visit will be considered valid. In the case of sensitization to animal dander, inclusion may be accepted provided that the patient has no habitual contact with such animals and that there is no possibility of this occurring during follow-up. Sensitization to pollens that overlap the grass season will not be considered an exclusion criterion, except when there is concomitant sensitization to Cupressus arizonica, ash, plane tree, and/or oak (considering results from the last 6 months or from the prick test performed in the study with supplied allergens) whose pollen seasons occur during the patient follow-up period
- Nasal hyperreactivity, defined as a non-specific response whereby the negative control induces a reaction corresponding to ≥50% of the positive response observed during the nasal provocation test.
- Recent nasal/oral surgery (within 6 months or less; in the case of dental extractions, dental implants, or similar procedures, within the last 2 months).
- Nasal septum perforation
- Partially controlled or uncontrolled bronchial asthma according to GINA criteria, including subjects with FEV1 ≤ 70% of predicted, FVC ≤ 80% of predicted, and receiving any asthma treatment other than short-acting β2-adrenergic bronchodilators (SABAs) used as rescue medication.
- Usual contraindications for allergen immunotherapy: Active or controlled neoplastic disease diagnosed within the last 5 years, Acute psychiatric pathology limiting the patient’s normal daily activity, Pregnancy and lactation
- Chronic use of medication that prevents adequate analysis and follow-up during the study: antihistamines, oral, inhaled and/or parenteral corticosteroids, membrane stabilizers (cromoglycates), antidepressants
- Refusal to participate in the trial and to sign informed consent
- Known allergy to components of the investigational product other than the study allergen
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Yet Recruiting | 01 Sept 2026 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo | Placebo | SUBLINGUAL SPRAY, SOLUTION | SUBLINGUAL USE | 0.2 | 4 | PRD12431363 |
Vacuna Phleum pratense 3000 TBU/ml | Test | SUBLINGUAL SPRAY | SUBLINGUAL USE | 0.2 | 4 | PRD13173151 |
Vacuna Phleum pratense 6000 TBU/ml | Test | SUBLINGUAL SPRAY, SOLUTION | SUBLINGUAL USE | 0.2 | 4 | PRD13177627 |
Test de provocación nasal Phleum pratense | Other | POWDER FOR SOLUTION FOR INHALATION | NASAL USE | 0.8 | 1 | PRD13177727 |
Vacuna Phleum pratense 1000 TBU/ml | Test | SUBLINGUAL SPRAY, SOLUTION | SUBLINGUAL USE | 0.2 | 4 | PRD13172903 |