Clinical Trial Results:
A multicentre, double-blind, placebo-controlled, randomized trial to assess the efficacy and tolerability of two dosing regimens of AllerT, a combination of contiguous overlapping peptides derived from Bet v 1, in adult subjects allergic to birch pollen

Trial information Top of page
Trial identification
Sponsor protocol code	AN004T
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01720251
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Anergis SA
Sponsor organisation address	Route de la Corniche 4, EPALINGES, Switzerland, 1066
Public contact	Vincent Charlon, Anergis SA, +41 216519220, vincent.charlon@anergis.ch
Scientific contact	Vincent Charlon, Anergis SA, +41 216519220, vincent.charlon@anergis.ch
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	31 Mar 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	14 Jun 2013
Global end of trial reached?	Yes
Global end of trial date	30 Jun 2013
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To demonstrate the efficacy of a two months pre-seasonal treatment with AllerT 100 µg maintenance dose in reducing symptoms of allergic rhinoconjunctivitis during the following birch pollen season
Protection of trial subjects	N/A
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	01 Oct 2012
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Poland: 86
Country: Number of subjects enrolled	Sweden: 33
Country: Number of subjects enrolled	Denmark: 46
Country: Number of subjects enrolled	France: 13
Country: Number of subjects enrolled	Latvia: 39
Country: Number of subjects enrolled	Lithuania: 21
Country: Number of subjects enrolled	Switzerland: 2
Worldwide total number of subjects	240
EEA total number of subjects	238
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	240
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Man or woman aged 18 to 55 years • Presenting moderate to severe allergic rhinoconjunctivitis to birch pollen confirmed at screening by meeting all of the following criteria: - An RSS  12 for the 2 preceding birch pollen seasons based on subject’s interview by the investigator - Previous use of anti-allergy medication during the 2 preceding b
Pre-assignment
Screening details	Man or woman aged 18 to 55 years • Presenting moderate to severe allergic rhinoconjunctivitis to birch pollen confirmed at screening by meeting all of the following criteria: - An RSS  12 for the 2 preceding birch pollen seasons based on subject’s interview by the investigator - Previous use of anti-allergy medication during the 2 preceding b
Pre-assignment period milestones
Number of subjects started	240
Number of subjects completed	240
Period 1
Period 1 title	overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Data analyst
Arms
Are arms mutually exclusive	Yes
Arm title	AllerT 100
Arm description	AllerT 100 ug target dose
Arm type	Experimental
Investigational medicinal product name	AllerT
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	5 injections on days 1, 7, 14, 28, 56 Target doses: half dose on Day 1 and full dose on days 7, 14. 28. 56 unless adjusted due to adverse events
Arm title	AllerT 50 ug
Arm description	AllerT target dose 50 ug
Arm type	Experimental
Investigational medicinal product name	AllerT
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	5 injections on days 1, 7, 14, 28, 56 Target doses: half dose on Day 1 and full dose on days 7, 14. 28. 56 unless adjusted due to adverse events
Arm title	placebo
Arm description	placebo control
Arm type	Placebo
Investigational medicinal product name	placebo with alhydrogel
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	placebo containing alhydrogel
Number of subjects in period 1 AllerT 100 AllerT 50 ug placebo Started 82 79 79 Completed 82 79 79

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	AllerT 100
Reporting group description	AllerT 100 ug target dose
Reporting group title	AllerT 50 ug
Reporting group description	AllerT target dose 50 ug
Reporting group title	placebo
Reporting group description	placebo control
Reporting group values AllerT 100 AllerT 50 ug placebo Total Number of subjects 82 79 79 240 Age categorical Units: Subjects     In utero 0 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0 0     Newborns (0-27 days) 0 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0 0     Children (2-11 years) 0 0 0 0     Adolescents (12-17 years) 0 0 0 0     Adults (18-64 years) 82 79 79 240     From 65-84 years 0 0 0 0     85 years and over 0 0 0 0 Age continuous Units: years     median (full range (min-max)) 36.5 (29 to 44) 37.5 (28 to 44) 33 (27 to 39) - Gender categorical Units: Subjects     Female 43 36 41 120     Male 39 43 38 120

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	AllerT 100
Reporting group description	AllerT 100 ug target dose
Reporting group title	AllerT 50 ug
Reporting group description	AllerT target dose 50 ug
Reporting group title	placebo
Reporting group description	placebo control

End points Top of page

Primary: CSMS Top of page
End point title	CSMS
End point description
End point type	Primary
End point timeframe	daily combined symptom and medication score measured daily during the birch pollen season and averaged during the season defined on pollen counts in the air
End point values AllerT 100 AllerT 50 ug placebo Number of subjects analysed 70 70 71 Units: score     least squares mean (standard deviation) 0.73 ± 0.583 0.63 ± 0.512 0.87 ± 0.616
Statistical analysis title	modified ITT
Comparison groups	AllerT 100 v AllerT 50 ug v placebo
Number of subjects included in analysis	211
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.05
Method	ANCOVA
Parameter type	Mean difference (final values)
Confidence interval

Primary: CSMS Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	treatment period up until 4 weeks later or till the last visit of the trial 2-4 weeks after the end of the birch pollen season
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	15
Reporting groups
Reporting group title	placebo
Reporting group description	-
Reporting group title	50 ug
Reporting group description	patients treated with AllerT 50 ug target dose group
Reporting group title	100 ug
Reporting group description	patients treated with AllerT 100 ug target dose group
Serious adverse events placebo 50 ug 100 ug Total subjects affected by serious adverse events      subjects affected / exposed 0 / 79 (0.00%) 1 / 78 (1.28%) 2 / 82 (2.44%)      number of deaths (all causes) 0 0 0      number of deaths resulting from adverse events Injury, poisoning and procedural complications Skull fracture      subjects affected / exposed 0 / 79 (0.00%) 0 / 78 (0.00%) 1 / 82 (1.22%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 Immune system disorders Hypersensitivity Additional description: allergic reaction      subjects affected / exposed 0 / 79 (0.00%) 1 / 78 (1.28%) 1 / 82 (1.22%)      occurrences causally related to treatment / all 0 / 0 1 / 1 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events placebo 50 ug 100 ug Total subjects affected by non serious adverse events      subjects affected / exposed 59 / 79 (74.68%) 70 / 78 (89.74%) 70 / 82 (85.37%) General disorders and administration site conditions Injection site reaction      subjects affected / exposed 53 / 79 (67.09%) 53 / 78 (67.95%) 51 / 82 (62.20%)      occurrences all number 79 93 94 Respiratory, thoracic and mediastinal disorders Respiratory disorder      subjects affected / exposed 15 / 79 (18.99%) 39 / 78 (50.00%) 47 / 82 (57.32%)      occurrences all number 18 62 88 Skin and subcutaneous tissue disorders Pruritus      subjects affected / exposed 3 / 79 (3.80%) 20 / 78 (25.64%) 11 / 82 (13.41%)      occurrences all number 3 30 19 Infections and infestations Rhinitis      subjects affected / exposed 7 / 79 (8.86%) 22 / 78 (28.21%) 25 / 82 (30.49%)      occurrences all number 8 45 54 Nasopharyngitis      subjects affected / exposed 14 / 79 (17.72%) 13 / 78 (16.67%) 16 / 82 (19.51%)      occurrences all number 15 16 19

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

More information Top of page