Subcutaneous Immunotherapy in Patients Sensitized to Phleum Pratense

Study Overview
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Brief Summary
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Based on EMA (European Medicines Agency) new guidelines on the clinical development of products for immunotherapy for the treatment of allergic disease the aim of this study was to assess safety and tolerability of three different subcutaneous immunotherapy dose escalations in patients allergic to the pollen of Phleum pratense.

Official Title
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Multicentre Phase I Randomized Double Blind Placebo Controlled Study of Subcutaneous Immunotherapy in Subjects With Allergic Rhinoconjunctivitis ± Asthma Sensitised to Phleum Pratense.

Conditions
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Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must sign the informed consent form. Patients must be between 18 and 60 years of age. Patients who obtained a prick test result greater or equal to 3 mm diameter and a specific IgE greater or equal to class 2 (CAP/PHADIA) to Phleum pratense. Patients with seasonal allergic rhinoconjunctivitis against Phleum pratense during a minimum of 2 years prior to study participation. Although allergic rhinoconjunctivitis is the pathology under study, the inclusion of patients with mild or moderate concomitant asthma is allowed. Patients will preferably be monosensitized to Phleum pratense. Polysensitized patients to other seasonal allergens will be accepted if sensitizations are caused by Pollens whose seasons do not overlap with Phleum pratense. Polysensitized patients to perennial allergens will also be accepted if not clinically relevant during the study period. Women of childbearing potential must have a negative urine pregnancy test at Screening visit/Visit 0 Women of childbearing potential must agree to use an appropriate contraception method during the study if they are sexually active. Exclusion Criteria: Stable and continued use of medication for allergic pathology during 2 weeks prior to inclusion. Patients sensitised to other overlapping seasonal allergens and with specific IgE levels greater or equal to class 2 CAP/PHADIA. Patients who received immunotherapy in the previous 5 years for Phleum pratense or for any allergen with cross reactivity or patients that are currently receiving immunotherapy for any allergen. Patients with severe asthma or FEV1 lower than 60% or asthma requiring inhaled or systemic corticoid treatment at the time of study entry or within 8 weeks prior to treatment commencement. Patients with: immunological, cardiac, renal or hepatic illnesses or any other medical condition that the investigator deems relevant so as to interfere with the study. Patients with a previous history of anaphylaxis Patients with unstable angina Patients with uncontrolled hypertension Patients with clinically significant arrythmias Patients with neoplasia Patients with clinically relevant malformations of the upper respiratory tract. Other chronic or immunological disease that could interfere with the assessment of the investigation product or that could generate any additional risk for the patient Patients who have participated in another clinical trial within 3 month prior to enrolment. Patients under treatment with tricyclic antidepressives, psychotropics or beta-blockers Female patients who are pregnant or breast-feeding or women of childbearing potential that do not agree to use an appropriate contraception method during the study if they are sexually active, if they have not been surgical sterilised or present any other incapacity to bear Patient who does not attend the visits Patient's lack of collaboration or refusal to participate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A active<br>6 administrations and 5 weeks duration Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals. | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|
| Placebo Comparator: Group A placebo<br>6 administrations and 5 weeks duration Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals. | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|
| Experimental: Group B active<br>8 administrations and 7 weeks duration Vial 1: 0.2 ml at 1 week intervals Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|
| Placebo Comparator: Group B placebo<br>8 administrations and 7 weeks duration Vial 1: 0.2 ml at 1 week intervals Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|
| Experimental: Group C active<br>8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks. Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval Week 3: vial 3 - 2 dose of 0.1 ml with 30 minute interval Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|
| Placebo Comparator: Group C placebo<br>8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks. Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval Week 3: vial 3 - 2 dose of 0.1 ml with 30 minute interval Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval | Biological: Subcutaneous immunotherapy with Phleum pratense pollen extract<br>* Increasing doses up to a maximum dose of 500 TSU<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and seriousness of both local and systemic adverse reactions |  | From informed consent signature (V0) until the end of patient participation in the study (depending on the treatment assigned between 4 and 8 weeks ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulin levels (IgE specific, IgG total and IgG4) and prick test dose response |  | Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic rhinitis, Phleum pratense, Timothy grass pollen allergy, subcutaneous immunotherapy