Clinical trial NCT01567306: Phase II Trial With Subcutaneous Immunotherapy in Patients Sensitized to Phleum Pratense
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinoconjunctivitis
Keywords: Allergy
Allergic rhinoconjunctivitis
Subcutaneous Immunotherapy
Phleum pratense pollen extract
Lead sponsor: Roxall Medicina España S.A
Sponsor class: INDUSTRY
First posted: 2012-03-30
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Based on EMA (European Medicines Agency) new guidelines on the clinical development of products for immunotherapy for the treatment of allergic diseases the aim of this study is to establish a dose-response relationship for clinical efficacy of Phleum pratense pollen extract subcutaneous vaccine.

Detailed description: In adherence to EMA guidelines, the Phase I Clinical trial was carried out using Phleum pratense extract in depot presentation using 3 different dose escalation scheme. The objective was to compare tolerance and safety of the three dose escalation scheme as well as to determine the maximum dose tolerated by the population.

Once the range of tolerated doses was established, and following the strict norms of the EMA, a Phase II dose response clinical trial was designed wherein the efficacy of subcutaneous immunotherapy in depot presentation could be compared in 5 different doses. One of these doses will be the MTD established by the population in the first study, another will be lower than this dose, and three will be greater than it. The dose escalation scheme to be tested was chosen based on the results of the aforementioned clinical trial. As dictated by EMA norms, a control placebo will be used.

Eligibility criteria: Inclusion Criteria:

1. Patients must sign the Informed Consent Form.
2. Patients must be between 18 and 60 years of age.
3. Patients with seasonal allergic rhinoconjunctivitis produced by Phleum pratense during at least 2 years prior to participating in the study. Although the pathology being studied is allergic rhinoconjunctivitis, patients who have concomitant mild or moderate asthma may be included.
4. Patients who have had a skin prick test result equal or more than 3 mm in diameter against Phleum pratense.
5. Patients who have specific IgE equal or more than class 2 (CAP/PHADIA) to Phleum pratense.
6. Patients will preferably be monosensitized to Phleum pratense. Polysensitized patients may only be included in the study if their other sensitizations are produced by:

   * Overlapping seasonal pollens which are cross-reactive with Phleum pratense.
   * Pollens whose seasons do not overlap with Phleum pratense and which are not expected to produce symptoms during the study period.
   * Other allergens which are not expected to produce symptoms during the study period.
7. Women of child-bearing potential must have a negative urine pregnancy test at the time they begin the study.
8. Furthermore, women of child-bearing potential must agree to use adequate contraceptive methods during this study if they are sexually active.

Exclusion Criteria:

1. Patients with stable and continued use of allergy medication during the 2 weeks prior to their inclusion in the study.
2. Patients sensitized to allergens with overlapping seasons but which are not cross-reactive with Phleum pratense and with specific IgE levels equal or less than class 2 CAP/PHADIA.
3. Patients who have received immunotherapy in the 5 years prior to the study against either the allergen being tested or an allergen which is cross-reactive, or who are currently receiving immunotherapy for any other allergen.
4. Patients with severe asthma or FEV1 \< 70% or with asthma which requires treatment with inhaled or systemic corticoids at the time of the study or in the 8 weeks immediately prior to the onset of treatment.
5. Patients with immunological, cardiac, renal or hepatic diseases or any with any other illness which the investigators deem may interfere with the study.
6. Patients with a prior history of anaphylaxis.
7. Patients with chronic urticaria.
8. Patients with moderate-severe atopic dermatitis.
9. Patients with clinically relevant malformations of the upper respiratory tract.
10. Patients who have participated in another clinical trial within 3 months prior to this study.
11. Patients being treated with tricyclic antidepressants, psychotropic drugs, beta-blockers, or angiotensin-converting enzyme inhibitors (ACEIs).
12. Women who are pregnant or breast-feeding or are of child-bearing age and who do not agree to use adequate contraception if they are sexually active and who have not demonstrated that they have been surgically sterilized or have other means of not bearing children.
13. Patients who cannot attend study visits.
14. Patients who are uncooperative or refuse to participate in the study.

Primary outcomes:
measure: Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV).
timeFrame: Baseline (V0) and Final Visit (FV). The Final Visit will be conducted within 7 plus minus 2 days after the last dose is administered. The study will be carried out outside the pollination season of Phleum pratense.
Secondary outcomes:
measure: 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.
timeFrame: From baseline (V0) to final visit (VF). The Final Visit will be conducted within 7 plus minus 2 days after the last dose is administered. All AE should be monitored until they are satisfactorily resolved or stabilized after the final visit of the study
Other outcomes:
Locations:
city: Coimbra
country: Portugal
facility: Hospital da Universidade de Coimbra
city: Porto
country: Portugal
facility: Centro Hospitalar de S. João
city: Senhora da Hora
country: Portugal
facility: Instituto CUF Porto
city: Setúbal
country: Portugal
facility: Centro Hospitalar de Setúbal - Hospital de São Bernardo
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar Gaia/Espinho
city: Talavera de la Reina
country: Spain
facility: Hospital Ntra. Sra. del Prado
state: Toledo
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: Emilio Alvarez Cuesta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Santiago Quirce, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Puerta de Hierro
name: Matilde Rodríguez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Gregorio Marañón
name: José Manuel Zubeldia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Ntra. Sra. del Prado
name: Carmen Panizo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto CUF Porto
name: João Fonseca, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar de S. João
name: José Luís Plácido, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar Gaia/Espinho
name: José Alberto Ferreira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital da Universidade de Coimbra
name: Celso Pereira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Hospitalar de Setúbal - Hospital de São Bernardo
name: Filipe Inácio, MD
role: PRINCIPAL_INVESTIGATOR
References: