Clinical Trial Results:
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of intraseasonal specific short-term immunotherapy with depigmented glutaraldehyde polymerized birch pollen allergenic extract (Depiquick® Birch) in patients with allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma.
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Summary
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EudraCT number |
2011-004185-14 |
Trial protocol |
DE |
Global end of trial date |
16 Jul 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Apr 2016
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First version publication date |
15 Apr 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CDPG103ADE01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01902992 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111 ,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111 ,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Jul 2012
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Jul 2012
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objective of the study was to assess the efficacy and safety of a depigmented and polymerized allergenic extract of 100% birch pollen in subjects suffering from tree pollen-induced allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma when specific immunotherapy (SIT) started intra-seasonally.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. Subjects were allowed to take rescue medication such as antihistamines, corticosteroids and beta-2 agonist on an as-needed basis for symptoms of birch pollen allergic rhinitis and/or rhinoconjunctivitis, asthma between study visits.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Mar 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 202
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Worldwide total number of subjects |
202
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EEA total number of subjects |
202
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
185
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 35 active centres in Germany. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 325 subjects were screened, of which 202 were randomized while 123 were screen failures and excluded from the study. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Data analyst, Assessor | |||||||||||||||||||||
Blinding implementation details |
The identity of the treatments was concealed by the use of study drugs that were identical in packaging, labeling, schedule of administration, appearance, taste and odor. Unblinding was allowed only in case of subjects emergencies and at the conclusion of the study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Birch allergen extract | |||||||||||||||||||||
Arm description |
Birch allergen extract aqueous solution (0.5 ml) was administered weekly via subcutaneous (s.c.) route for 5 weeks. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Birch allergen extract
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Investigational medicinal product code |
DPG103
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Placebo matched to birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
Placebo
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo matched to birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Birch allergen extract
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Reporting group description |
Birch allergen extract aqueous solution (0.5 ml) was administered weekly via subcutaneous (s.c.) route for 5 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo matched to birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Birch allergen extract
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Reporting group description |
Birch allergen extract aqueous solution (0.5 ml) was administered weekly via subcutaneous (s.c.) route for 5 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo matched to birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks. | ||
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End point title |
Combined Symptom and Medication Score for rhinitis/rhinoconjunctivitis (SMSrhi) in full analysis set | ||||||||||||
End point description |
The combined SMS represented the sum of symptom severity and rescue medication score. The symptom severity score consisted of 6 items measured on a 4-point scale (0: absent symptoms to 3- severe symptoms) and rescue medication score was derived from average of daily rescue medication scores during the pollen season. The combined score for SMS ranged from 0 to 36 (symptom severity score range 0 to 18 and rescue medication score range 0 to 18). A lower score indicated an improvement in the allergic condition. The analysis was performed in full analysis set (FAS) population, defined as all randomized subjects who received at least one dose of study drug and had a baseline and at least one post-baseline assessment for the primary efficacy parameter.
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End point type |
Primary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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Statistical analysis title |
Treatment comparisons for SMSrhi | ||||||||||||
Comparison groups |
Birch allergen extract v Placebo
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Number of subjects included in analysis |
202
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.8878 | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Least square mean difference | ||||||||||||
Point estimate |
0.06
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.73 | ||||||||||||
upper limit |
0.84 | ||||||||||||
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End point title |
Combined SMS for rhinitis/rhinoconjunctivitis with a certain median symptom score | ||||||||||||
End point description |
The combined SMS represented the sum of symptom severity and rescue medication score. The symptom severity score consisted of 6 items measured on a 4-point scale (0: absent symptoms to 3- severe symptoms) and a median cut-off score was defined after the pollen season on the basis of blinded data. Rescue medication score was derived from average of daily rescue medication scores during the pollen season. The combined score for SMS ranged from 0 to 36 (symptom severity score range 0 to 18 and rescue medication score range 0 to 18). A lower score indicated an improvement in the allergic condition. The analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Symptom score for rhinitis/rhinoconjunctivitis (Srhi) and for asthma (Sast) based on pollen grain count | ||||||||||||||||||
End point description |
The symptom severity score (Srhi and Sast) was derived from subject diaries with ratings for 6 symptoms of rhinitis/rhinoconjunctivits (nasal itching, nasal sneezing, rhinorrhea, nasal obstruction, ocular itching/grittiness/redness, and ocular tearing) and 4 asthma symptoms (chest tightness, shortness of breath, cough, and wheezing). Subjects rated the symptoms on a 4-point scale: 0 - absent symptoms (no sign/symptom evident), 1: mild symptoms (sign/symptom clearly present, but minimal awareness; easily, tolerated), 2: moderate symptoms (definite awareness of, sign/symptom that is bothersome but, tolerable), 3: severe symptoms (sign/symptom hard to tolerate; causes interference with, activities of daily living and/or sleeping). The symptom severity score ranged from 0 to 18. A lower score indicated an improvement in the allergic condition. The analysis was performed on FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Symptom score for rhinitis/rhinoconjunctivitis (Srhi) and for asthma (Sast) based on median symptom score | ||||||||||||||||||
End point description |
The symptom severity score (Srhi and Sast) was derived from subject diaries with ratings for 6 symptoms of rhinitis/rhinoconjunctivits and 4 asthma symptoms. Subjects rated the symptoms on a 4-point scale: 0 - absent symptoms, 1: mild symptoms, 2: moderate symptoms and 3: severe symptoms. The symptom severity and asthma score ranged from 0 to 18. Symptom severity scores were analyzed on the basis of all days with a median symptom score of at least 3. The analysis was performed on FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Medication score for rhinitis/rhinoconjunctivitis (Mrhi) and for asthma | ||||||||||||||||||
End point description |
The rescue medication score was defined as mean score of daily rescue medication utilized for relief from rhinitis/rhinoconjuctivitis (Mrhi) and asthma symptoms (Mast) during the pollen season. The improvement in symptoms post administration of any rescue medication were rated by subjects on a 4-point scale: 0- no improvement, 1- slight improvement, 2- good improvement and 3- vast improvement. The rescue medication score ranged from 0 to 18. A lower score indicated an improvement in the allergic condition. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Medication score for rhinitis/rhinoconjunctivitis (Mrhi) and for asthma (Mast) based on median symptom score | ||||||||||||||||||
End point description |
The rescue medication score was defined as mean score of daily rescue medication utilized for relief from rhinitis/rhinoconjuctivitis (Mrhi) and asthma symptoms (Mast) during the pollen season. The improvement in symptoms post administration of any rescue medication were rated by subjects on a 4-point scale: 0- no improvement, 1- slight improvement, 2- good improvement and 3- vast improvement. The rescue medication score ranged from 0 to 18. Rescue medication scores were analyzed on the basis of all days with a median symptom score of at least 3. A lower score indicated an improvement in the allergic condition. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Subject's assessed time to onset of action | ||||||||||||
End point description |
The time to onset of action was defined as the time from date of randomization to the date of event defined as the first documented onset of action. The subjects documented the onset of action as response to the following question: Do you have the feeling that your allergy symptoms are better today due to the injections (immunotherapy)? If a subject had no event, time to onset of action was censored at the date of last adequate assessment of the SMS for rhinitis/rhinoconjunctivitis. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 92
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of well days | ||||||||||||
End point description |
Well days during the tree pollen season were defined as the days with a symptom score less than 2 and no rescue medication intake. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of relevant pollen exposition time
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Subject’s and investigator's assessment of global efficacy of treatment | |||||||||||||||||||||||||||||||||||||||
End point description |
The subjects and investigators assessed the overall impression of the therapy efficacy as excellent/ good/ moderate/ poor or unacceptable. Analysis was performed on FAS population.
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End point type |
Secondary
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End point timeframe |
Day 92
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title |
Change from baseline in health related quality of life (HRQoL) total score at Week 7 | ||||||||||||
End point description |
HRQoL was assessed in adults and adolescent subjects by the rhinitis/rhinoconjunctivitis quality of life questionnaire (RQLQ) and adolescent rhinoconjunctivitis quality of life questionnaire (AdolRQLQ) respectively. The RQLQ, a 28-item disease-specific questionnaire and AdolRQLQ comprising of 25 item disease specific questionnaire measured the functional impairments on a 6-point scale for each item. The overall score of a questionnaire was the mean response of all 28 or 25 items, respectively. Changes in scores of 0.5 to 1.0 were considered clinically meaningful; 1.0 to 1.5 as moderate and greater than (>) 1.5 as marked clinically important differences for overall summary score. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 7
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline in health related quality of life (HRQoL) domain scores at Week 7 | |||||||||||||||||||||||||||||||||
End point description |
HRQoL was assessed in adults and adolescent subjects by the RQLQ and AdolRQLQ respectively. The RQLQ, a 28-item disease-specific questionnaire and AdolRQLQ comprising of 25 item disease specific questionnaire measured the functional impairments divided in 7 domains (activities, sleep, common complaints, practical problems, nasal symptoms, ocular symptoms and emotions) on a 6-point scale for each item. Each domain score was the mean response to all the items in that domain. Changes in scores of 0.5 to 1.0 were considered clinically meaningful; 1.0 to 1.5 as moderate and >1.5 as marked clinically important differences for overall summary score. Analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 7
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
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End point title |
Subject's assessed medication scores for rhinitis/rhinoconjuctivitis (M-sub-rhi) and asthma (M-sub-ast) | ||||||||||||||||||
End point description |
Subjects self-assessed the improvement in the allergic symptoms of rhinitis/rhinoconjuctivitis (M-sub-rhi) and asthma (M-sub-ast) post administration of rescue medication. The medication score assessment was based on Likert scale, 0-no improvement, 1-mild improvement, 2-good improvement and 3-enormous improvement. The range of the medication score for rhinitis/ rhinoconjunctivitis complaints was 0–15 (five possible rescue medications with a score from 0–3) and for asthma synptoms was 0-9 (3 possible medications with a score from 0-3). The range of the rescue medication by intake for rhintis/rhinoconjuctivitis and asthma was 0–18 and 0-12, respectively. M-sub-rhi and M-sub-ast was determined as: medication score/ intake scores. A higher medication score indicated improvement in allergic condition. The analysis was performed in FAS population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively.
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End point type |
Secondary
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End point timeframe |
From Day 1 to end of secondary pollen exposition time
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Birch allergen extract
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Reporting group description |
Birch allergen extract aqueous solution (0.5 ml) was administered weekly via subcutaneous (s.c.) route for 5 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo matched to birch allergen extract aqueous solution (0.5 ml) was administered weekly via s.c. route for 5 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Feb 2012 |
To implement changes concerning the selection of study population, the protocol version 00, dated 23-Jan-2012, was amended and resulted in study protocol version 01, dated 01-Feb-2012. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
