Allergic Rhinoconjunctivitis
Conditions
Keywords
Allergy, Allergic rhinoconjunctivitis, Subcutaneous Immunotherapy, Phleum pratense pollen extract
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.
Interventions
BIOLOGICALAllergovac Depot
Increasing dosages till the maintenance dose of 0.25 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals.
BIOLOGICALPlacebo
Increasing volumes of placebo. Afterwards, 3 maintenance doses are given at 4-weekly intervals.
Sponsors
Roxall Medicina España S.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 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. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 | 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. |
Countries
Portugal, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Allergovac Depot Group 1 Active Allergovac Depot: Increasing dosages till the maintenance dose of 0.25 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals. | 27 |
| Allergovac Depot Group 2 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. | 25 |
| Allergovac Depot Group 3 Active Allergovac Depot: Increasing dosages till the maintenance dose of 1SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals. | 24 |
| Allergovac Depot Group 4 Active Allergovac Depot: Increasing dosages till the maintenance dose of 2 SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals. | 24 |
| Allergovac Depot Group 5 Active Allergovac Depot: Increasing dosages till the maintenance dose of 4SPT is reached. Afterwards, 3 maintenance doses are given at 4-weekly intervals. | 25 |
| Placebo - Group 6 Placebo: Increasing volumes of placebo. Afterwards, 3 maintenance doses are given at 4-weekly intervals. | 26 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 4 | 1 |
| Overall Study | Change site living | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 2 | 0 | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Allergovac Depot Group 1 Active | Allergovac Depot Group 2 Active | Allergovac Depot Group 3 Active | Allergovac Depot Group 4 Active | Allergovac Depot Group 5 Active | Placebo - Group 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 27.4 years STANDARD_DEVIATION 7.7 | 31.8 years STANDARD_DEVIATION 9.9 | 34.8 years STANDARD_DEVIATION 9 | 33.5 years STANDARD_DEVIATION 9.4 | 34.9 years STANDARD_DEVIATION 8.3 | 35.0 years STANDARD_DEVIATION 10 | 32.9 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 10 Participants | 9 Participants | 7 Participants | 8 Participants | 8 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 15 Participants | 17 Participants | 17 Participants | 18 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 16 Participants | 10 Participants | 12 Participants | 15 Participants | 88 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 8 Participants | 14 Participants | 13 Participants | 11 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 25 | 0 / 24 | 0 / 24 | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 8 / 27 | 15 / 25 | 7 / 24 | 3 / 24 | 3 / 25 | 4 / 26 |
| serious Total, serious adverse events | 1 / 27 | 2 / 25 | 2 / 24 | 3 / 24 | 8 / 25 | 1 / 26 |
Outcome results
Primary
Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV).
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).
Time frame: 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.
Population: Intent-to-treat population (ITT): This population included all randomized patients who received at least one treatment dose and who presented baseline and post-baseline values for the primary efficacy variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allergovac Depot Group 1 Active | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 0.493 SPT | Standard Deviation 2.06 |
| Allergovac Depot Group 2 Active | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 0.275 SPT | Standard Deviation 2.884 |
| Allergovac Depot Group 3 Active | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 0.693 SPT | Standard Deviation 2.142 |
| Allergovac Depot Group 4 Active | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 0.876 SPT | Standard Deviation 2.414 |
| Allergovac Depot Group 5 Active | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 1.385 SPT | Standard Deviation 2.17 |
| Placebo - Group 6 | Variation of the Concentration of Phleum Pratense Extract Needed to Produce a Positive Nasal Provocation Test From Baseline (V0) to Final Visit (FV). | 0.839 SPT | Standard Deviation 2.328 |
Secondary
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.
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.
Time frame: 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