The active treatment arm receive active phleum pollen immunotherapy (Depigoid 100% phleum). Depigmented and polymerized allergen extract of Phleum pollen for subcutaneous injection.

This arm receive DEPIGOID Placebo during the first year, and DEPIGOID Phleum during the second year of study.
DEPIGOID Placebo contains the same composition as in the active DEPIGOID Phleum with the only difference being the exclusion of the phleum pollen allergen extract.

Allergic Rhinitis

Subcutaneous Immunotherapy with modified extract of Phleum pollen.

DEPIGOID phleum

DEPIGOID Placebo

Hospital Infanta Leonor

Hospital Regional Universitario Carlos Haya

Efficacy of a Depigmented Extract of Phleum in Local Allergic Rhinitis

Efficacy of a Depigmented Extract of Phleum in the Treatment of Local Allergic Rhinitis

Patients were provided a diary to score the severity of their symptoms and the use of rescue medication during 4 weeks in two consecutive springs.
Nasal symptoms of rhinorrhea, nasal congestion, sneezing, nasal itching, and ocular symptoms were recorded using a 4-point categorical scale from 0 to 3 (0: no symptoms, 1:mild, 2:moderate; 3:severe).
The use of rescue medication was recorded in the patient diary according to the following score:
Oral antihistamines (1 tablet = 1 point); intranasal corticosteroids (400mcg/day of beclometasone or equivalent = 1.4 points); and ocular antihistamines (1 dose = 1 point).

The response to NAPT-Phl with increasing concentrations of phleum pratense (0.001-0.01-0.05-0.1 mcg/ml) will be evaluated by nasal symptoms and acoustic rhinometry.

Miguel Blanca Gomez

Director Allergy Unit

Plaza del Hospital Civil

Laboratorios Leti, S.L.

Allergic Rhinitis Due to Grass Pollens

Grazax

Placebo

Hospital Universitario de La Princesa

Hospital Clínico Universitario San Carlos

Molecular and Cellular Mechanism in the Course of Immunotherapy With a Phleum Pratense Oral Lyophilisate

ALK-Abelló A/S

Allergic Rhinitis/Rhinoconjunctivitis +- Intermittent Asthma

Sensitization Against Phleum Pratense Pollen

Dose-Finding Study

Suspension for subcutaneous injection Build-up phase (day 1): 0,1mL + 0,2mL + 0,2mL s.c.injections in intervals of 30 minutes Maintenance phase: 5x single s.c. injection of 0,5mL every 4 weeks

Depigoid Phleum

Hippke, Ear-Nose-Throat specialist

Zentrum für Rhinologie und Allergie

Dose Finding Study Depigoid Phleum: 4 Doses in Patients With Allergic Rhinitis/Rhinoconjunctivitis +-Asthma

A Randomised, Double-Blind, Parallel Group, Multicentre Study to Assess the Efficacy and Safety of Four Concentrations of Depigoid® Phleum in Patients With Allergic Rhinitis and/or Rhinoconjunctivitis With or Without Intermittent Asthma

Comparison between dosage groups: percentage of patients who need an increased amount of allergen to provoke a positive CPT at the end of the treatment (comparison slope of efficacy). It is expected that at the end of the study higher doses are necessary to provoke a positive CPT.
According to the EMA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies.

Analysis of individual results for allergen amount

At the end of the study investigator and patient will give their general overall impression on the safety of the study treatment on a 4-point scale (excellent, good, moderated, unacceptable).
Results will be compared between dosage groups

AEs are recorded at the study visits (patients are questioned and the patient diary - where specific allergic symptoms should be recorded by the patients during 48hrs after each injection of IMP - is assessed by the investigator and AEs recorded in the CRF if applicable) and at any time of the study when site becomes aware of an Ae/SAE.
AE/SAE rate is compared between treatment groups (safety profile. Also rates of local and systemic reactions will be calculated.

Symptoms: - at injection site, - of the skin (not injection site), - of the nose, - of the eyes, - of the lung/respiratory system, other symptoms Symptoms documented in the diary will be judged and assessed by the investigator and - if applicable - transcribed as AE into the CRF.
Medication: Antihistaminics (eye drops, nose spray or tablet), Sultanol, oral corticosteroid and intake of other medication documented in the diary are to be transcribed to the CRF

Leti Pharma GmbH

Allergovac Depot: Increasing dosages till the maintenance dose of 0.25 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot Group 1 Active

Allergovac Depot: Increasing dosages till the maintenance dose of 0.5 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot Group 2 Active

Allergovac Depot: Increasing dosages till the maintenance dose of 1SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot Group 3 Active

Allergovac Depot: Increasing dosages till the maintenance dose of 2 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot Group 4 Active

Allergovac Depot: Increasing dosages till the maintenance dose of 4SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot Group 5 Active

Placebo: Increasing volumes of placebo. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Placebo - Group 6

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Variation of the concentration of Phleum pratense extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). The changes will be compared among groups (including the placebo group).

Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV).

All adverse reactions and/or events were recorded both by the patient and the health care personnel responsible for the administration of the subcutaneous immunotherapy. The incidence and intensity of adverse events was compared among the treatment groups.

All Adverse Reactions and or Events Will be Recorded Both by the Patient and the Health Care Personnel Responsible for the Administration of the Subcutaneous Immunotherapy.

Overall Study

Dr. M Cruz Gómez project manager of Roxall Medicina España S.A.

Allergic Rhinoconjunctivitis

Increasing dosages till the maintenance dose of 0.25 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Allergovac Depot

Increasing dosages till the maintenance dose of 0.5 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Increasing dosages till the maintenance dose of 1SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Increasing dosages till the maintenance dose of 2 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Increasing dosages till the maintenance dose of 4SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Increasing volumes of placebo. Afterwards, 3 maintenance doses are given at 4-weekly intervals.

Hospital da Universidade de Coimbra

Centro Hospitalar de S. João

Instituto CUF Porto

Centro Hospitalar de Setúbal - Hospital de São Bernardo

Centro Hospitalar Gaia/Espinho

Hospital Ntra. Sra. del Prado

Hospital Universitario Gregorio Marañón

Hospital Universitario Ramón y Cajal

Hospital Universitario La Paz

Hospital Universitario Puerta de Hierro

Phase II Trial With Subcutaneous Immunotherapy in Patients Sensitized to Phleum Pratense

Phase II, Multicenter, Randomized, Double Blind Study, With Subcutaneous Immunotherapy At Different Doses, in Parallel Groups and Placebo-Controlled, in Patients With Rhinoconjunctivitis ± Asthma Sensitized to Phleum Pratense

Roxall Medicina España S.A

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.

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

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

Increasing doses up to a maximum dose of 500 TSU

Subcutaneous immunotherapy with Phleum pratense pollen extract

Hospital Ramón y Cajal

Subcutaneous Immunotherapy in Patients Sensitized to Phleum Pratense

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

Suspension for Injection, Every 6 weeks for one year

Avanz Phleum pratense

UntersuchungsZentrum für Dermatologie, Allergologie und Asthma

Avanz Phleum Pratense Maintenance Dose

Allergy

Skin prick test of extracts of allergens in 4 tenfold dilutions. Assessment wheal size after 15 minutes

Extracts of allergens

Zentrum für klinische Forschung Clinical Trials Center, University Hospital and University Zurich

Biological Standardization of Allergen Extracts of Pollens of Betula Pendula, Phleum Pratense and Mite Extract of Dermatophagoides Pteronyssinus

Biological Standardization of Allergen Extracts of Pollens of Betula Pendula, Phleum Pratense and Mite Extract of Dermatophagoides Pteronyssinus in Patients With Rhinoconjunctivitis With/ Without Asthma Sensitized to Betula Pendula, Dermatophagoides Pteronyssinus and Phleum Pratense An Open-label, Single-center Study

The primary efficacy variable will be the wheal size area of the immediate phase reaction in mm2

University Hospital, Zürich

Skin prick test of extracts of allergens in 4 tenfold dilutions.

The first active arm will receive a dose that is 10x less than the dose of the other arm

The first active arm will receive a dose that is 10x more than the dose of the other arm

Rhinitis, Allergic, Seasonal

Conjunctivitis, Allergic

Asthma

Immunotherapy with modified extract of P. pratense pollen

Hospital Clínico de Salamanca

Immunotherapy With Depigmented and Polymerized Allergen Extract of Phleum Pratense

Immunotherapy With Depigmented and Polymerized Allergen Extract of Phleum Pratense in Patients Suffering From Allergic Rhinoconjunctivitis and/or Asthma

phleum alpinum/hypersensitivity