Allergic Rhinoconjunctivitis
Conditions
Keywords
Allergy, Immunotherapy, Allergic Rhinoconjunctivitis, D. pteronyssinus, house dust allergy
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 was to assess safety and tolerability of 3 different subcutaneous immunotherapy dose escalations in patients allergic to Dermatophagoides pteronyssinus.
Interventions
BIOLOGICALsubcutaneous immunotherapy with DPT extract
Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units)
BIOLOGICALSubcutaneous depot placebo
Increasing doses of subcutaneous depot placebo in three different scales
Sponsors
Roxall Medicina España S.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with allergic rhinoconjunctivitis with or without asthma against DPT during a minimum of 1 year prior to study participation. 2. Patients must sign the informed consent form. 3. Patients must be between 18 and 60 years of age. 4. 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 DPT. 5. Patients will preferably be monosensitized to DPT. In the case of polysensitized patients they can only be included if other sensitizations are caused by seasonal allergens whose pollination do not overlap with the study period. 6. Women of childbearing potential must have a negative urine pregnancy test at Screening visit/Visit 0 7. Women of childbearing potential must agree to use an appropriate contraception method during the study if they are sexually active
Exclusion criteria
1. Stable and continued use of medication for allergic pathology during 2 weeks prior to inclusion. 2. Patients sensitised to other perennial allergens clinically relevant and with specific IgE levels greater or equal to class 2 CAP/PHADIA. 3. Patients who received immunotherapy in the previous 5 years for DPT or for any allergen with cross reactivity or patients that are currently receiving immunotherapy for any allergen. 4. Patients with severe asthma or FEV1 minor than 70% or asthma requiring inhaled or systemic corticoid treatment at the time of study entry or within 8 weeks prior to treatment initiation. 5. 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. 6. Patients with a previous history of anaphylaxis 7. Patients with chronic urticaria 8. Patients with unstable angina 9. Patients with uncontrolled hypertension 10. Patients with clinically significant arrythmias 11. Patients with neoplasia 12. Patients with clinically relevant malformations of the upper respiratory tract. 13. Other chronic or immunological disease that could interfere with the assessment of the investigational product or that could generate any additional risk for the patients 14. Patients who have participated in another clinical trial within 3 month prior to enrolment. 15. Patients under treatment with tricyclic antidepressives, psychotropics beta-blockers, or Angiotensin Converting Enzyme Inhibitors (ACEI) 16. 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 surgically sterilised or present any other incapacity to bear 17. Patient who does not attend the visits 18. Patient's lack of collaboration or refusal to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 ) | The primary end points were the number of ARs and the severity of local and systemic ARs (SARs) to SCIT administration. Proportions were compared between study arms. The tolerability of SCIT was evaluated by early and late local reactions (i.e., local swelling and redness) and systemic reactions after each injection (any symptoms from organs distant from the location of the injection). Reactions were classified depending on the severity and onset of the reaction, according to the EAACI classification (Alvarez-Cuesta 2006). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunoglobulin Levels (IgE Specific) Active Versus Placebo | Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks) | Changes on immunoglobulin level determinations (specific IgE, IgG and IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo. |
| Immunoglobulin Levels (IgG Total) Active Versus Placebo | Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks) | Changes on immunoglobulin level determinations (IgG) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo. |
| Immunoglobulin Levels (IgG 4) Active Versus Placebo | Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks) | Changes on immunoglobulin level determinations (IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Active 6 administrations and 5 weeks duration
1. Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals
2. Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals.
subcutaneous immunotherapy with DPT extract: Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units) or placebo | 12 |
| Group B Active 8 administrations and 7 weeks duration
1. Vial 1: 0.2 ml at 1 week intervals
2. Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals
3. Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals
subcutaneous immunotherapy with DPT extract: Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units) or placebo | 12 |
| Group C Active 8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks.
1. Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval
2. Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval
3. Week 3: vial 3 - 2 doses of 0.1 ml with 30 minute interval
4. Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval
subcutaneous immunotherapy with DPT extract: Increasing doses of subcutaneous immunotherapy in three different scales up to the maximum dose of 500 TSU (Treatment Standardized Units) or placebo | 12 |
| Group A Placebo 6 administrations and 5 weeks duration
1. Vial 2: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals
2. Vial 3: 0.1 ml, 0.2 ml and 0.5 ml at 1 week intervals.
Subcutaneous depot placebo | 4 |
| Group B Placebo 8 administrations and 7 weeks duration
1. Vial 1: 0.2 ml at 1 week intervals
2. Vial 2: 0.1 ml, 0.2 ml, 0.4 ml at 1 week intervals
3. Vial 3: 0.1 ml, 0.2 ml, 0.4 ml and 0.5 ml at 1 week intervals
subcutaneous depot placebo | 4 |
| Group C Placebo 8 administrations, 2 administrations in the same day. 1 week interval between 2 doses, during 3 weeks.
1. Week 1: vial 2 - 2 administrations of 0.1 ml with 30 minute interval
2. Week 2: vial 2 - 0.2 ml and 0.3 ml with 30 minute interval
3. Week 3: vial 3 - 2 doses of 0.1 ml with 30 minute interval
4. Week 4: vial 3 - 0.2 ml and 0.3 ml with 30 minute interval
subcutaneous depot placebo | 4 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 0 | 3 | 0 |
| Overall Study | Concomitant disease | 0 | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A Active | Group B Active | Group C Active | Group A Placebo | Group B Placebo | Group C Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.66 years STANDARD_DEVIATION 8.93 | 30.88 years STANDARD_DEVIATION 9.77 | 31.80 years STANDARD_DEVIATION 8.85 | 33.93 years STANDARD_DEVIATION 9.49 | 33.93 years STANDARD_DEVIATION 9.49 | 33.93 years STANDARD_DEVIATION 9.49 | 32.68 years STANDARD_DEVIATION 9.34 |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 7 Participants | 3 Participants | 2 Participants | 1 Participants | 24 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 5 Participants | 1 Participants | 2 Participants | 3 Participants | 24 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 / 12 | 0 / 12 | 0 / 12 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 12 / 12 | 11 / 12 | 8 / 12 | 1 / 4 | 2 / 4 | 1 / 4 |
| serious Total, serious adverse events | 1 / 12 | 3 / 12 | 3 / 12 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Number and Seriousness of Both Local and Systemic Adverse Reactions
The primary end points were the number of ARs and the severity of local and systemic ARs (SARs) to SCIT administration. Proportions were compared between study arms. The tolerability of SCIT was evaluated by early and late local reactions (i.e., local swelling and redness) and systemic reactions after each injection (any symptoms from organs distant from the location of the injection). Reactions were classified depending on the severity and onset of the reaction, according to the EAACI classification (Alvarez-Cuesta 2006).
Time frame: From informed consent signature (V0) until the end of patient participation in the study (depending on the treatment assigned between 4 and 8 weeks )
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 2 adverse reactions number |
| Group A Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 4 adverse reactions number |
| Group B Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 1 adverse reactions number |
| Group B Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 6 adverse reactions number |
| Group C Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 0 adverse reactions number |
| Group C Active | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 4 adverse reactions number |
| Group A Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 1 adverse reactions number |
| Group A Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 0 adverse reactions number |
| Group B Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 1 adverse reactions number |
| Group B Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 1 adverse reactions number |
| Group C Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Local adverse reactions number | 0 adverse reactions number |
| Group C Placebo | Number and Seriousness of Both Local and Systemic Adverse Reactions | Systemic adverse reactions number | 1 adverse reactions number |
Secondary
Immunoglobulin Levels (IgE Specific) Active Versus Placebo
Changes on immunoglobulin level determinations (specific IgE, IgG and IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.
Time frame: Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A Active | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | 0.0750 ng/mL | Standard Deviation 0.393 |
| Group B Active | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | -0.0055 ng/mL | Standard Deviation 0.013 |
| Group C Active | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | 0.1709 ng/mL | Standard Deviation 0.274 |
| Group A Placebo | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | -0.1445 ng/mL | Standard Deviation 0.639 |
| Group B Placebo | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | -0.0398 ng/mL | Standard Deviation 0.507 |
| Group C Placebo | Immunoglobulin Levels (IgE Specific) Active Versus Placebo | 0.0395 ng/mL | Standard Deviation 0.039 |
Secondary
Immunoglobulin Levels (IgG 4) Active Versus Placebo
Changes on immunoglobulin level determinations (IgG4) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.
Time frame: Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A Active | Immunoglobulin Levels (IgG 4) Active Versus Placebo | -1.0878 ng/mL | Standard Deviation 0.77 |
| Group B Active | Immunoglobulin Levels (IgG 4) Active Versus Placebo | 0.0838 ng/mL | Standard Deviation 0.518 |
| Group C Active | Immunoglobulin Levels (IgG 4) Active Versus Placebo | -1.2885 ng/mL | Standard Deviation 0.844 |
| Group A Placebo | Immunoglobulin Levels (IgG 4) Active Versus Placebo | 0.0770 ng/mL | Standard Deviation 0.162 |
| Group B Placebo | Immunoglobulin Levels (IgG 4) Active Versus Placebo | -0.8243 ng/mL | Standard Deviation 0.663 |
| Group C Placebo | Immunoglobulin Levels (IgG 4) Active Versus Placebo | 0.0580 ng/mL | Standard Deviation 0.039 |
Secondary
Immunoglobulin Levels (IgG Total) Active Versus Placebo
Changes on immunoglobulin level determinations (IgG) from basal visit to final visit and changes in mean wheal area in prick test dose response from basal visit to final visit, active versus placebo.
Time frame: Before (V0) and after treatment (depending on the treatment assigned between 4 and 8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A Active | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.8813 ng/mL | Standard Deviation 0.484 |
| Group B Active | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.0405 ng/mL | Standard Deviation 0.097 |
| Group C Active | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.9589 ng/mL | Standard Deviation 0.536 |
| Group A Placebo | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.0953 ng/mL | Standard Deviation 0.137 |
| Group B Placebo | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.4918 ng/mL | Standard Deviation 0.389 |
| Group C Placebo | Immunoglobulin Levels (IgG Total) Active Versus Placebo | -0.0425 ng/mL | Standard Deviation 0.09 |