Allergic Rhinoconjunctivitis
Conditions
Brief summary
The purpose of this study is to assess the tolerability of AVANZ.
Detailed description
To assess the tolerability of the up-dosing phase of AVANZ Phleum pratense. The frequency of patients with adverse reactions will be the study primary endpoint.
Interventions
AVANZ Phleum pratense up-dosing phase (300, 600, 3000, 6000 and 15,000 SQ+) + one 15,000 SQ+ maintenance injection
Sponsors
ALK-Abelló A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* History of grass pollen rhinoconjunctivitis * Positive SPT to Phleum pratense * Positive specific IgE against Phleum pratense
Exclusion criteria
* Uncontrolled severe asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Subjects With Adverse Drug Reactions | 6 weeks | Frequency of patients with adverse reactions, local or systemic |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Subjects With Systemic Reactions | 6 weeks | Frequency of patients with systemic reactions, based on EAACI classification: Grade I (mild systemic reaction) to IV (anaphylactic shock) |
| Frequency of Subjects With Local Adverse Reaction | 6 weeks | Frequency of patients with local adverse reactions |
| Change in Phleum Pratense Specific IgE-blocking Factor | baseline (visit 1) and at 6 weeks (visit 6) | IgE-blocking factor measures the amount of IgE bound to the allergen in the presence of allergen-competing factors present in the serum of a subject treated with allergen immunotherapy. The test is based in a double IgE measurement, an ordinary assay and an assay in the presence of competing components and takes the form of: IgE blocking factor = 1 - (Competitive IgE/Ordinary IgE). Theoretical limits are from 0 (no IgE blocked) to 1 (all IgE blocked) and, being a ratio, is a dimensionless measure |
| Change in Phleum Pratense Specific IgG4 | baseline (visit 1) and at 6 weeks (visit 6) | — |
| Change in Immediate Cutaneous Response to Phleum Pratense | baseline (visit 1) and at 6 weeks (visit 6) | Wheal size provoked after prick test with 4, 20 and 100 µg/ml Phl p 5 allergen extracts analysed by Parallel Line Assay. Cutaneous Tolerance Index (CTI) is the factor it is necessary to multiply the extract concentration by after SCIT (V6) to obtain the same response in terms of wheal area as at baseline (V1). CTI, being an index, is a dimensionless measure. A CTI of 1 indicates no change in skin sensitivity while if higher than 1 a decrease in skin sensitivity (it would be needed a more concentrated allergen extract at V6 to elicit the same skin response as at V1 |
Countries
Spain
Participant flow
Pre-assignment details
199 subjects were recruited and 3 resulted screening failures so 196 subjects started the trial. Four subjects discontinued before treatment so 192 subjects were treated. The reason for discontinuation for these 4 subjects was withdrawal of consent (Withdrawal by subject, included in Reasons Not Completed)
Participants by arm
| Arm | Count |
|---|---|
| AVANZ Phleum Pratense AVANZ Phleum pratense
AVANZ Phleum pratense: Up-dosing phase of AVANZ Phleum pratense | 192 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Delay in IMP administration | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | AVANZ Phleum Pratense |
|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment Spain | 192 participants |
| Sex: Female, Male Female | 98 Participants |
| Sex: Female, Male Male | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 109 / 192 |
| serious Total, serious adverse events | 3 / 192 |
Outcome results
Primary
Frequency of Subjects With Adverse Drug Reactions
Frequency of patients with adverse reactions, local or systemic
Time frame: 6 weeks
Population: Subjects treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVANZ Phleum Pratense | Frequency of Subjects With Adverse Drug Reactions | 133 participants |
Secondary
Change in Immediate Cutaneous Response to Phleum Pratense
Wheal size provoked after prick test with 4, 20 and 100 µg/ml Phl p 5 allergen extracts analysed by Parallel Line Assay. Cutaneous Tolerance Index (CTI) is the factor it is necessary to multiply the extract concentration by after SCIT (V6) to obtain the same response in terms of wheal area as at baseline (V1). CTI, being an index, is a dimensionless measure. A CTI of 1 indicates no change in skin sensitivity while if higher than 1 a decrease in skin sensitivity (it would be needed a more concentrated allergen extract at V6 to elicit the same skin response as at V1
Time frame: baseline (visit 1) and at 6 weeks (visit 6)
Population: Participants in which results of the Parallel Line Assay are valid
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AVANZ Phleum Pratense | Change in Immediate Cutaneous Response to Phleum Pratense | 1.79 CTI, Cutaneous Tolerance Index |
Comparison: Parallel Line Assay is based on the construction of two dose-response regression lines obtained plotting the allergen concentration used to prick test the subjects against the wheal size obtained. ANOVA allows to check for regression, linearity and parallelism. A common slope and y-intercepts are calculated. The CTI is the exponentiation of the difference between y-intercepts divided by the common slope. (Finney D.J., Statistical Method in Biological Assay, 1978).p-value: <0.01Parallel Line Assay
Secondary
Change in Phleum Pratense Specific IgE-blocking Factor
IgE-blocking factor measures the amount of IgE bound to the allergen in the presence of allergen-competing factors present in the serum of a subject treated with allergen immunotherapy. The test is based in a double IgE measurement, an ordinary assay and an assay in the presence of competing components and takes the form of: IgE blocking factor = 1 - (Competitive IgE/Ordinary IgE). Theoretical limits are from 0 (no IgE blocked) to 1 (all IgE blocked) and, being a ratio, is a dimensionless measure
Time frame: baseline (visit 1) and at 6 weeks (visit 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVANZ Phleum Pratense | Change in Phleum Pratense Specific IgE-blocking Factor | Visit 1 | -0.13 arbitrary units | Standard Deviation 0.2 |
| AVANZ Phleum Pratense | Change in Phleum Pratense Specific IgE-blocking Factor | Visit 6 | 0.12 arbitrary units | Standard Deviation 0.3 |
Comparison: The null hypothesis is no changes in IgE-blocking factor values from visit 1 (baseline) to visit 6 (end of treatment) versus the alternative hypothesis of change in IgE-blocking factor valuesp-value: <0.001t-test, 2 sided
Secondary
Change in Phleum Pratense Specific IgG4
Time frame: baseline (visit 1) and at 6 weeks (visit 6)
Population: Number of subject with valid data in visit 1 and visit 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AVANZ Phleum Pratense | Change in Phleum Pratense Specific IgG4 | Visit 1 | 0.44 mgA/l | Standard Deviation 0.6 |
| AVANZ Phleum Pratense | Change in Phleum Pratense Specific IgG4 | Visit 6 | 2.26 mgA/l | Standard Deviation 2.5 |
Comparison: The null hypothesis is no changes in Phleum specific IgG4 values from visit 1 (baseline) to visit 6 (end of treatment) versus the alternative hypothesis of change in Phleum specific IgG4 valuesp-value: <0.001t-test, 2 sided
Secondary
Frequency of Subjects With Local Adverse Reaction
Frequency of patients with local adverse reactions
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVANZ Phleum Pratense | Frequency of Subjects With Local Adverse Reaction | 109 participants |
Secondary
Frequency of Subjects With Systemic Reactions
Frequency of patients with systemic reactions, based on EAACI classification: Grade I (mild systemic reaction) to IV (anaphylactic shock)
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AVANZ Phleum Pratense | Frequency of Subjects With Systemic Reactions | 66 participants |