Clinical Trials Register

Summary
EudraCT Number:	2012-001651-39
Sponsor's Protocol Code Number:	BIGRADE-IHR-12
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-30
Trial results	View 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-001651-39

A.3

Full title of the trial

In-vivo biological standardization of Dermatophagoides, Betulaceae and Graminaceae extracts for the determination of the biological activity in HEP units

Standardizzazione biologica in-vivo di estratti di dermatofagoidi, betulacee e graminacee per la determinazione dell'attivitÃƒÂ biologica in unitÃƒÂ HEP

A.3.1

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

Biological standardization of Dermatophagoides, Betulaceae and Graminaceae

Standardizzazione biologica di estratti allergenici di dermatofagoidi, betulacee e graminacee.

A.3.2

Name or abbreviated title of the trial where available

BIGRADE-IHR -12

A.4.1

Sponsor's protocol code number

BIGRADE-IHR-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	LOFARMA
B.1.3.4	Country	Italy
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	LOFARMA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LOFARMA
B.5.2	Functional name of contact point	Servizio medico
B.5.3	Address:
B.5.3.1	Street Address	VIALE CASSALA 40
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20143
B.5.3.4	Country	Italy
B.5.4	Telephone number	02-58198211
B.5.5	Fax number	02-8322512
B.5.6	E-mail	marco.bruno@lofarma.it

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	Allergenic extract of Dermatophagoides
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Solution for skin-prick test
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Allergenic extracts of Dermatophagoides, Betulaceae and Graminaceae.
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	.4
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	Allergenic extract of Betulaceae
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Solution for skin-prick test
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Allergenic extracts of Dermatophagoides, Betulaceae and Graminaceae.
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	.4
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	Allergenic extract of Graminaceae
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Solution for skin-prick test
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	Allergenic extracts of Dermatophagoides, Betulaceae and Graminaceae.
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	.4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Respiratory allergopathy

Allergopatia respiratoria

E.1.1.1

Medical condition in easily understood language

Patients with respiratory allergopathy clinically relevant and sensitized to at least one of the allergens Dermatophagoides, Betulaceae and Graminaceae.

Soggetti affetti da allergopatia respiratoria clinicamente rilevante e sensibilizzati ad almeno uno degli allergeni dermatofagoidi, betulacee e graminacee.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10054928
E.1.2	Term	Allergy to plants
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10001742
E.1.2	Term	Allergy to animal
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

Determination of the biological activity of allergenic extracts of Dermatophagoides, Betulaceae and Graminaceae in HEP units (histamine equivalent prick) in order to define an in-house reference preparation (IHRP).

Determinazione della attività biologica di estratti allergenici di dermatofagoidi, pollini di betulacee e graminacee in unità HEP (histamine equivalent prick) allo scopo di definire un in-house reference preparation (IHRP).

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. subjects of both sexes, of any ethnicity, aged between 18 and 50 years (median between 20 and 30 years) with a documented history of at least two years of related allergopatia respiratory exposure to at least one of the allergens tested (Dermatophagoides, Betulaceae and Graminaceae) and who lives in areas where the presence of such allergens represents a significant problem, which is presented in a row; 2. prick-test positive with average diameter (half-sum of the larger diameter and diameter perpendicular to it) of the wheal procured from an extract already standardized, and available commercially, the allergen to be tested ≥ 3 mm, average diameter of the wheal procured by histamine dihydrochloride 1 mg / ml (H1)> 4 mm and a mean diameter of the wheal procured from the negative control (N) <3 mm; 3. intact skin in places of execution of the test; 4. informed consent signed and dated

1. soggetti di entrambi i sessi, di qualunque etnia, di età compresa fra 18 e 50 anni (mediana tra 20 e 30 anni) con una storia documentata di almeno due anni di allergopatia respiratoria correlata all’esposizione verso almeno uno degli allergeni da testare (dermatofagoidi, betulacee, graminacee) e che vivano in aree dove la presenza di tali allergeni rappresenti una problematica di rilievo, che si presentino in modo consecutivo; 2. prick-test positivo con diametro medio (semisomma del diametro maggiore e diametro ad esso ortogonale) del ponfo procurato da un estratto già standardizzato, e disponibile commercialmente, dell’allergene da testare ≥ 3 mm, diametro medio del ponfo procurato da istamina diidrocloruro 1 mg/ml (H1) > 4 mm e diametro medio del ponfo procurato dal controllo negativo (N) < 3 mm; 3. cute integra nelle sedi di esecuzione dei test; 4. consenso informato firmato e datato.

E.4

Principal exclusion criteria

1. simultaneous participation in other clinical trials or studies completed less than one month prior to enrollment; 2. previous immunotherapy in the last 5 years with a preparation of allergen known to interfere with the allergens to be tested; 3. immunotherapy in progress; 4. individuals with any relationship or dependence by the sponsor and / or investigator; 5. no pregnant or breast feeding patients; 6. immunodeficiency (eg induced by immunosuppressive drugs); 7. atopic dermatitis; 8. dermographism, 9. hives; 10. neurological and infectious diseases that can produce cutaneous anergy; 11. Abuse of alcohol or drugs; 12. taking medications that may interfere with skin reactivity; 13. treatment with tricyclic antidepressants or tetracyclic, phenothiazines, β-blockers, dopamine, clonidine, corticosteroids (> 10 mg / day of prednisone); 14. should be suspended any oral antihistamines and topical corticosteroids for at least 7 days; 15. exposure of the execution venues to test UV rays, artificial or natural, for therapeutic or aesthetic within 4 weeks.

1. partecipazione contemporanea ad altri studi clinici, o a studi conclusi meno di un mese prima dell’arruolamento; 2. precedente immunoterapia negli ultimi 5 anni con una preparazione di allergene noto per interferire con gli allergeni da testare; 3. immunoterapia in corso; 4. soggetti con qualunque rapporto o dipendenza dallo sponsor e/o dall’investigator; 5. donne in gravidanza e/o in allattamento; 6. immunodeficienza (ad esempio indotta da farmaci immunosoppressivi); 7. dermatite atopica; 8. dermografismo, 9. orticaria; 10.malattie neurologiche ed infettive che possano produrre anergia cutanea; 11. abuso di alcol o droghe; 12. assunzione di farmaci che possano interferire con la reattività cutanea; 13. trattamento con farmaci antidepressivi triciclici o tetraciclici, fenotiazine, β-bloccanti, dopaminergici, clonidina, corticosteroidi orali (> 10 mg/die di prednisone); 14. dovranno essere sospesi eventuali farmaci antistaminici orali e cortisonici topici da almeno 7 giorni ; 15. esposizione delle sedi di esecuzione dei test a raggi UV, artificiali o naturali, a scopo terapeutico o estetico entro le 4 settimane.

E.5 End points

E.5.1

Primary end point(s)

Calculate the concentration of allergen can cause a response of an average diameter equal to that of the reaction caused by histamine.

Calcolare la concentrazione di allergene in grado di provocare una risposta di diametro medio pari a quello della reazione provocata dall’istamina.

E.5.1.1

Timepoint(s) of evaluation of this end point

The avarage diameter in mm of local skin reaction during the immediate phase of the reaction, ie 15 minutes from the execution of the test.

Il diametro medio in mm della cutireazione locale, sarà calcolato durante la fase immediata della reazione, cioè a 15 minuti dall'esecuzione del test.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.5

Efficacy

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

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:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-10-30.

Yes

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

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)

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

2012-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-19

P. End of Trial
P.	End of Trial Status	Completed

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