Clinical Trials Register

Summary
EudraCT Number:	2010-020693-42
Sponsor's Protocol Code Number:	VO68.10
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-09-10
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2010-020693-42

A.3

Full title of the trial

A randomised, double-blind, placebo-controlled, multi-national, Phase IIIb study to assess the sustained clinical effect and safety of sublingual immunotherapy administered as birch pollen extract solution at a dose of 300 I.R. once daily to patients suffering from birch pollen-induced rhinoconjunctivitis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A placebo controlled study to assess after two years of treatment the efficacy and safety of a birch pollen extract solution at a dose of 300IR taken under the tongue and once daily by patients with birch pollen related rhinoconjunctivitis.

A.3.2

Name or abbreviated title of the trial where available

V068.10

A.4.1

Sponsor's protocol code number

VO68.10

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Stallergenes S.A.
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Stallergenes
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Stallergenes SA
B.5.2	Functional name of contact point	Medical Department
B.5.3	Address:
B.5.3.1	Street Address	6, rue Alexis de Tocqueville
B.5.3.2	Town/ city	Antony Cedex
B.5.3.3	Post code	92183
B.5.3.4	Country	France
B.5.4	Telephone number	+33 1 55 59 20 00
B.5.5	Fax number	+33 1 55 59 20 68

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	STALORAL Birch 10 I.R./ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Stallergenes GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Birch Pollen Allergen Extract
D.3.9.1	CAS number	8000045252
D.3.9.3	Other descriptive name	ALLERGENS, POLLEN & PLANT EXTRACT
D.3.10	Strength
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10 IR/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	STALORAL Birch 300 I.R./ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Stallergenes GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	8000045252
D.3.9.3	Other descriptive name	ALLERGENS, POLLEN & PLANT EXTRACT
D.3.10	Strength
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300 IR/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral drops, solution
D.8.4	Route of administration of the placebo	Sublingual use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Birch pollen allergic Rhinoconjunctivitis

E.1.1.1

Medical condition in easily understood language

rhinoconjunctivitis due to birch pollen allergy

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10066093
E.1.2	Term	Birch pollen allergy
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of the trial is to assess the sustained clinical efficacy on the Average Adjusted Symptom Score (AAdSS): a score taking into account the daily Rhinoconjunctivitis Total Symptom Scores (RTSSs) and daily rescue medication usage of a 300 IR dose of a birch pollen allergen extract sublingual solution, administered once daily during 5 months per year, after 2 consecutive years in patients with birch pollen allergy.

E.2.2

Secondary objectives of the trial

The Average Adjusted Symptom Score AAdSS on non-primary efficacy analysis sets and/or other evaluation periods. The Average Adjusted Symptom Score AAdSS in three subgroups of pooled sites grouped according to the mean AAdSS in the placebo group (AAdSS by tertiles).The Average Rhinoconjunctivitis Total Symptom Score ARTSS of the six rhinoconjunctivitis symptoms sneezing, rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus and watery eyes The Average Rescue Medication Score ARMS and use of rescue medication Each of the six individual Average Rhinoconjunctivitis Symptom Scores ARSS. The Average Combined Score ACS: A score taking into account the Rhinoconjunctivitis Total Symptom Score RTSS and the Rescue Medication Score RMS The intensity of Rhinoconjunctivitis symptoms using a Visual Analogue Scale RVAS score The standardized Rhinoconjunctivitis Quality of Life Questionnaire score RQLQ(S) The Proportion of Symptom-Controlled Days (PSCDs) To document the safety of the treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The main inclusion criteria are:
- Male or female outpatients aged 18 to 65 years (inclusive).
- Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the previous 2 pollen seasons requiring intake of symptomatic treatment.

- Sensitization to birch pollen demonstrated by:
•A positive SPT to birch pollen with wheal diameter > 3 mm.
•Birch pollen allergens specific IgE levels ≥ 0.70 kU/L.
- RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a maximum possible score of 18.
- Patients with an FEV1 ≥ 80% of the predicted value.
- Patients who are willing to comply with the protocol.
- Patients having given a signed informed consent before completing any study related procedure.

E.4

Principal exclusion criteria

Exclusion Criteria:
-Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season due to any other allergens (except alder and hazel). This includes patients with symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and living with these animals at home or at risk of frequent contacts with these animals (family, friends etc.) during the course of the study.
-Patient who previously received desensitization treatment to birch pollen and/or another Betulaceae sp. (for example hazel or alder) within the previous 5 years.
-Patients with ongoing treatment by immunotherapy with another allergen.
-Pregnancy (positive pregnancy test), breast-feeding.
-Female patients of childbearing potential planning a pregnancy during this study or not using a medically accepted contraceptive method (hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], intrauterine device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner).
- Patients planning to move during the study or planning to leave the area during the birch pollen season for more than 1 week (7 consecutive days).
- Patients with moderate or severe persistent asthma (GINA 3 or 4).
- Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide dose-equivalents.
- Patients with any nasal or oral condition that could interfere with the efficacy or safety assessments (such as nasal polyposis or oral inflammation).
- Patients with severe immune deficiency.
- Patients with a past or current disease, which as judged by the Investigator, may affect the patient’s participation in or outcome of this study.
- Any other disease or condition which would place a patient at undue risk by being included in the study (according to the Investigator’s opinion).
- Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy whatever the route and/or immunosuppressive drugs.
- Patients treated with inhaled/systemic steroids (whatever the indication) within 4 weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12 weeks before Visit 1 (Screening).
- Patients under continuous corticotherapy (inhaled or systemic drugs).
- Patients following a strict low sodium diet as the study treatment contains 590 mg of sodium chloride per vial in a 10 mL solution.
- Investigators, co-Investigators, as well as their children or spouses and all study collaborators.
- Patients who have participated in any clinical trial within 3 months prior to this one.

E.5 End points

E.5.1

Primary end point(s)

The Average Adjusted Symptom Score (AAdSS) while on treatment during the second pollen period is the primary efficacy endpoint for the sustained clinical efficacy.

E.5.1.1

Timepoint(s) of evaluation of this end point

end of study, after two years of treatment

E.5.2

Secondary end point(s)

ARTSS during the evaluation periods while the patient is on treatment.
ARMS during the evaluation periods while the patient is on treatment.
ARSS during the evaluation periods while the patient is on treatment.
ACS during the evaluation periods while the patient is on treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

end of study, after two years of treatment

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

544

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

544

F.4.2.2

In the whole clinical trial

544

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will return to standard care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-11-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-09-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-07-05

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