Clinical Trials Register

Summary
EudraCT Number:	2013-000487-28
Sponsor's Protocol Code Number:	VO72.12
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-05-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-000487-28

A.3

Full title of the trial

A dose ranging study investigating the efficacy and safety of sublingual
immunotherapy tablets of house dust mite allergen extracts in adults with house dust mite-associated allergic asthma

A.3.1

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

Study to investigate how efficient and how safe are tablets of house dust mite allergens for patients with house dust mite allergic asthma

A.3.2

Name or abbreviated title of the trial where available

A study of allergen extracts in house dust mite associated asthma

A.4.1

Sponsor's protocol code number

VO72.12

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 SA
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 S.A
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 S.A
B.5.2	Functional name of contact point	Global Clinical 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 55592
B.5.5	Fax number	+33 1 55592

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	No
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.3.1	Product name	Sublingual tablet of HDM Allergen Extracts
D.3.4	Pharmaceutical form	Sublingual tablet
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.3.9.3	Other descriptive name	Dermatophagoides pteronyssinus allergen extract
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Dermatophagoides farinae allergen extract
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	No
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.3.1	Product name	Sublingual tablet of HDM Allergen Extract
D.3.4	Pharmaceutical form	Sublingual tablet
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.3.9.3	Other descriptive name	Dermatophagoides Pteronyssinus allergen extract
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Dermatophagoides farinae allergen extract
D.3.9.4	EV Substance Code	AS4
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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: 3
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	No
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.3.1	Product name	Sublingual tablet of HDM allergen Extracts
D.3.4	Pharmaceutical form	Sublingual tablet
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.3.9.3	Other descriptive name	Dermatophagoides pteronyssinus allergen extract
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Dermatophagoides farinae allergen extract
D.3.9.4	EV Substance Code	AS6
D.3.10	Strength
D.3.10.1	Concentration unit	BAU Bioequivalent Allergy Unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
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	Sublingual tablet
D.8.4	Route of administration of the placebo	Sublingual use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Sublingual tablet
D.8.4	Route of administration of the placebo	Sublingual use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Sublingual tablet
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

House dust mite-associated allergic asthma

E.1.1.1

Medical condition in easily understood language

Asthma caused by an allergy to house dust mites

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10020419
E.1.2	Term	House dust mite allergy
E.1.2	System Organ Class	100000004870

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10001705
E.1.2	Term	Allergic asthma
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the effect of one year of treatment with sublingual immunotherapy tablets of house dust mite (HDM) allergen extracts at a daily dosage of 100 IR, 500 IR or 1000 IR as compared to placebo on the Asthma Control Test™ (ACT) score, in adults with HDM-associated allergic asthma.

E.2.2

Secondary objectives of the trial

To determine the effect and the safety of immunotherapy tablets of HDM allergen extracts administered sublingually at a daily dosage of 100 IR, 500 IR or 1000 IR as compared to placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent obtained before completion of any study-related procedure.
2. Male or female from 18 to 50 years of age, in general good health apart from his/her asthma history, as determined by medical history, physical examination and routine laboratory tests.
3. Medical history consistent with HDM-induced allergic asthma for at least one year before screening, as supported by clear evidence of a relationship between asthma symptoms and exposure to HDM allergens (see Appendix III for the conduct of subject’s interview).
4. Medical history consistent with HDM-induced allergic rhinitis for at least one year before screening, as supported by clear evidence of a relationship between rhinitis symptoms and exposure to HDM allergens.
5. Wheal diameter induced by Skin Prick Test (SPT) to Dermatophagoides pteronyssinus or to Dermatophagoides farinae at least 5 mm greater than the negative control and HDM-specific IgE serum value ≥ 0.7 kU/L.
6. Asthma therapies consistent with GINA treatment Step 2 to Step 4 provided that the controller medication consists of inhaled corticosteroid (ICS) alone or combined with long-acting beta (β)-2 agonist (LABA) (according to GINA classification, 2012), unchanged for at least 12 weeks before screening.
7. Spirometry (pre-bronchodilator) with best FEV1 ≥ 70% of the predicted value.
8. Spirometry with reversibility in FEV1 of ≥ 12% and ≥ 200 mL from the prebronchodilator value after inhalation of 200-400 mcg of salbutamol. If not recorded in the subject’s medical chart within two years prior to screening, FEV1 reversibility of
≥ 12% and ≥ 200 mL must be obtained at screening or during the screening period.
9. Asthma Control Test™ (ACT) score ≤ 19.
10. Subject willing to comply with the protocol.
11. Routine safety laboratory tests results within acceptable range.
12. Asthma Control Test™ (ACT) score ≥ 16 and ≤ 19.

E.4

Principal exclusion criteria

1. Treatment with systemic corticosteroids within 12 weeks before screening.
2. Asthma exacerbation requiring hospitalisation within 12 weeks before screening.
3. Lower respiratory tract infection within 4 weeks before screening.
4. History of Intensive Care Unit admission or intubation for asthma.
5. History of anaphylaxis.
6. Previous treatment with anti-IgE therapy.
7. Former smoker with > 10 pack/year history or current smoker.
8. A urine level of cotinine ≥ 500 ng/mL.
9. Co-sensitisation to any perennial aeroallergen to which the subject is regularly exposed, and which could significantly change the asthma symptoms of the subject during the study.
10. Co-sensitisation to any seasonal aeroallergen to which the subject could be exposed during the primary period of evaluation (approximately November to February), for example, specifically excluded will be subjects sensitised to parietaria, ragweed, or
mugwort, if this allergen is endemic to the investigative site’s region.
11. Allergen immunotherapy for HDM within the past 10 years.
12. Ongoing immunotherapy for an aeroallergen other than house dust mite.
13. Any oral condition that could confound the safety assessments i.e. oral inflammations such as oral lichen planus, oral ulcerations or oral mycosis, or planning to have a dental
extraction during the study.
14. Galactose intolerance.
15. Ongoing treatment with beta-blockers, tricyclic ntidepressants or monoamine oxidase inhibitors (MAOIs).
16. A serious immunopathologic condition or malignancy.
17. Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method (hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], intrauterine device,
spermicide used with a male condom, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner). Women are considered not to
have childbearing potential before their menarche, at least 2 years after menopause or if they have had a bilateral tubal ligation or a total hysterectomy or bilateral oophorectomy or ovariectomy.
18. Past or current disease, which as judged by the Investigator, may affect the subject’s participation in, or the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, immunosuppression,immunological disease and endocrine disease.
19. Participation in any clinical study within the 12 weeks before screening.
20. Possible dependency of the subject on sponsor or investigators/subinvestigators or study collaborators
21. Treatment with systemic corticosteroids between screening and randomisation.
22. Asthma exacerbation requiring hospitalisation between screening and randomisation.

E.5 End points

E.5.1

Primary end point(s)

Change of ACT Score from baseline

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 7 or early termination provided the IP has been taken for at least 4 weeks

E.5.2

Secondary end point(s)

1.Subjects achieving asthma control according to ACT score
2.Subjects with at least a 3-point improvement in ACT score
3.Daily and average daytime asthma symptom scores
4.Daily and average nighttime asthma symptom scores
5.Asthma rescue medication use
6.Asthma rescue medication score
7.Proportion of asthma symptom- and rescue medication-free days
8.Asthma exacerbations
9.Standardised Asthma Quality of Life Questionnaire (AQLQ(S))
10.SF-12 Health Survey
11.Controlled weeks
12.Six individual daily and average rhinoconjunctivitis symptom scores
13.Daily and average rhinitis total symptom scores
14.Daily and average conjunctivitis total symptom scores
15.Daily and average rhinoconjunctivitis total symptom scores
Rhinoconjunctivitis rescue medication usage
16.Daily and average rhinitis adjusted symptom scores
17.Daily and average rhinoconjunctivitis adjusted symptom scores
18.Daily and average rhinoconjunctivitis rescue medication scores
19.Daily and average rhinitis combined scores
20.Daily and average rhinoconjunctivitis combined scores
21.Proportion of rhinoconjunctivitis symptom-controlled days (PSCDs)
22.Controlled patients (CPs) regarding rhinoconjunctivitis
23.Standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S))

E.5.2.1

Timepoint(s) of evaluation of this end point

Endpoint 1: Visit 7 or early termination
Endpoints 2 to 7 and 12 to 23: visit 7
Endpoint 8: 1 year treatment
Endpoint 9: visits, 5, 6, 7 and EOT
Endpoint 11: weekly for the 12 previous weeks to visit 7

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1