Clinical Trials Register

Summary
EudraCT Number:	2015-002769-44
Sponsor's Protocol Code Number:	ESAP
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Restarted
Date on which this record was first entered in the EudraCT database:	2015-09-04
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

Austria - BASG

A.2

EudraCT number

2015-002769-44

A.3

Full title of the trial

Efficacy and safety of an accelerated outpatient protocol for
hymenoptera venom immunotherapy

Wirksamkeit und Sicherheit eines verkürzten ambulanten Impfschemas für die Immuntherapie mit Insektengift

A.3.1

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

Efficacy and safety of an shortened outpatient vaccination scheme for
therapy with insect poison

Wirksamkeit und Sicherheit einer verkürzten ambulanten Impfschmemas für die Therapie mit Insektengift

A.3.2

Name or abbreviated title of the trial where available

ESAP

A.4.1

Sponsor's protocol code number

ESAP

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	Medical University of Graz
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical University of Graz
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Graz
B.5.2	Functional name of contact point	Department of Dermatology
B.5.3	Address:
B.5.3.1	Street Address	Auenbruggerplatz 8
B.5.3.2	Town/ city	Graz
B.5.3.3	Post code	8036
B.5.3.4	Country	Austria
B.5.4	Telephone number	+436505142129
B.5.5	Fax number	+4331638512466
B.5.6	E-mail	gunter.sturm@medunigraz.at

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	ALUTARD SQ® Insekten
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abelló Allergie-Service GmbH, Bäckermühlweg 59, 4030 Linz
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Alutard SQ® 802 Vespula spp.
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VESPULA SPP
D.3.9.3	Other descriptive name	VESPULA SPP. (802)
D.3.9.4	EV Substance Code	SUB123383
D.3.10	Strength
D.3.10.1	Concentration unit	SQU/ml Standardised Quality Unit(s)/millilitre (Deprecated)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1000 to 100000
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	ALUTARD SQ® Insekten
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abelló Allergie-Service GmbH, Bäckermühlweg 59, 4030 Linz
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Alutard SQ® 801 Apis mellifera
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	APIS MELLIFERA (801)
D.3.9.3	Other descriptive name	APIS MELLIFERA (801)
D.3.9.4	EV Substance Code	SUB123149
D.3.10	Strength
D.3.10.1	Concentration unit	SQU/ml Standardised Quality Unit(s)/millilitre (Deprecated)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1000 to 100000
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Immunotherapy against systemic anaphylactic sting reactions

Immuntherapie gegen systemische anaphylaktische Stich-Reaktionen

E.1.1.1

Medical condition in easily understood language

Immunotherapy against serious sting reactions

Immuntherapie gegen schwere Stich-Reaktionen

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10001749
E.1.2	Term	Allergy to sting
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 primary objective of this study is to develop a short outpatient
protocol for the initial phase of hymenoptera venom immunotherapy
and to evaluate the efficacy and safety of this accelerated protocol

Das primäre Ziel der Studie ist es, ein kurzes ambulantes Protokoll für die Anfangsphase der Insektengift -Immuntherapie zu entwickeln und die Wirksamkeit und Sicherheit dieses verkürzten Protokolls zu evaluieren.

E.2.2

Secondary objectives of the trial

To evaluate efficacy of immunotherapy by sting challenges immediately after reaching the maintenance dose.
· To evaluate the frequency of side-effects within the first year of immunotherapy
(maintenance phase).
· To compare the frequency of side-effects with previously published protocols.
· To evaluate whether antihypertensive treatment with beta-blockers and/or ACE inhibitors is associated with a higher frequency and more severe side-effects during VIT.
· To evaluate whether the prevalence of cardiovascular diseases and/or pulmonary diseases is associated with a higher frequency and more severe side-effects during VIT.
· To evaluate whether high sIgE levels are associated with a higher frequency of sideeffects.
· To evaluate whether high tryptase levels are associated with a higher frequency of sideeffects

Die Wirksamkeit der Immuntherapie nach Stichprovokationen sofort nach Erreichen die Erhaltungsdosis zu bewerten.
· Die Häufigkeit von Nebenwirkungen innerhalb des ersten Jahres der Immuntherapie zu bewerten ( Erhaltungsphase ) .
· Die Häufigkeit von Nebenwirkungen, mit zuvor veröffentlichten Protokollen zu vergleichen.
· Zu bewerten, ob antihypertensive Behandlung mit Beta-Blockern und / oder ACE-Inhibitoren mit einer höheren Anzahl und schwereren Nebenwirkungen während der VIT verbunden ist.
· Zu bewerten , ob die Prävalenz von Herzkreislauferkrankungen und / oder Lungen-Erkrankungen mit einer höheren Anzahl und schwereren Nebenwirkungen während VIT verbunden ist.
· Zu bewerten , ob hohe sIgE-Werte mit einer höheren Frequenz an Nebenwirkungen verbunden sind.
· Zu bewerten , ob hohe Tryptase-Werte mit einer höheren Anzahl an Nebenwirkungen verbunden sind.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Legally competent male and female subjects with a history of systemic anaphylactic sting reaction (≥ grade I according to the classification of Ring and Messmer)
Age ≥18 and ≤70 years
Written consent of the participant after being informed

gesetzl. einwilligungsfähige Männer und Frauen mit der Anamneseeiner systemischen anaphylaktischen Stichreaktion (≥ Stufe I nach der Klassifizierung von Ring and Messmer)
Alter ≥18 und ≤70 Jahre
schiftliche Einwilligung nach Aufklärung

E.4

Principal exclusion criteria

Simultaneous participation in another clinical trial
Nursing women

Absolute contraindication(s) for VIT:
- Uncontrolled Asthma
- Autoimmune disorders in active forms (nonresponding to treatment)
- Pregnancy
- AIDS
· Pretreatment with Omalizumab

gleichzeitige Teilnahme in einer anderen klinischen Studie
stillende Frauen

Absolute Kontrainikation(en) für VIT:
- unkontrolliertes Asthma
- aktive Autoimmunerkrankungen (Nichtansprechen auf Medikamente)
- Schwangerschaft
- AIDS
Prämedikation mit Omalizumab

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint for the study is the presence of systemic anaphylactic reactions (grade
I-IV) during the initial phase of hymenoptera venom immunotherapy.
For the primary analysis the proportion of systemic anaphylactic reactions in the study group
will be evaluated for bee and wasp venom separately using a one-sided exact 97.5%
confidence interval.

Der primäre Endpunkt der Studie ist das Vorkommen von systemischen anaphylaktischen Reaktionen (Typ I-IV) in der Anfangsphase der Insektengift -Immuntherapie .
Für die primäre Analyse wird der Anteil systemischer anaphylaktischer Reaktionen in der Studiengruppe
für Bienen- und Wespengift separat über ein einseitiges genaues 97,5% Konfidenzintervall bewertet werden.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year after starting the immunotherapy

1 Jahr nach Beginn der Immuntherapie

E.5.2

Secondary end point(s)

The main secondary endpoint is the outcome of sting challenges after the inital phase
to check efficacy of immunotherapy.
Secondary endpoints will be analysed using the binomial test for categorical variables and
the t-test or the Wilcoxon rank sum tests for continuous variables.

Der wichtigste sekundäre Endpunkt ist das Ergebnis der Stichprovokationen nach der Initialphase um die Wirksamkeit der Immuntherapie zu überprüfen.
Sekundäre Endpunkte werden unter Verwendung des Binomialtests für kategoriale Variablen und des t-Tests oder des Wilcoxon-Rangsummentests für kontinuierliche Variablen analysiert .

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year after starting the immunotherapy

1 Jahr nach Beginn der Immuntherapie

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

Yes

E.6.4

Safety

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

Letzte Visite des letzten Patienten

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:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

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

152

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)

Standard medical care at the Department of Dermatology

Standard Behandlung auf der Abteilung für Dermatologie

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

2015-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-28

P. End of Trial
P.	End of Trial Status	Restarted

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