Clinical Trials Register

Summary
EudraCT Number:	2014-000097-19
Sponsor's Protocol Code Number:	TRANCHE
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-01-12
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

Germany - BfArM

A.2

EudraCT number

2014-000097-19

A.3

Full title of the trial

Open, comparative, randomized study on the efficacy, safety and bioavailability of highly concentrated inhaled epinephrine (4 mg L-epinephrine / ml, Infectokrupp® Inhal) versus epinephrine autoinjector application (Fastjekt® Junior) in infants with acute anaphylactic reaction during a food provocation

Offene, vergleichende, randomisierte Studie zur Wirksamkeit, Sicherheit und Bioverfügbarkeit von hochkonzentriertem inhalativen Epinephrin (4 mg L-Epinephrin/ml, Infectokrupp® Inhal) versus Epinephrin-Autoinjektor-Anwendung (Fastjekt® Junior) bei Kleinkindern mit akuter anaphylaktischer Reaktion im Rahmen einer Nahrungsmittelprovokation

A.3.1

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

A.4.1

Sponsor's protocol code number

TRANCHE

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	Charité Universitätsmedizin Berlin
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Klinik für Pädiatrie m. S. Pneumologie und Immunologie
B.5.2	Functional name of contact point	Prof. Dr. med. Kirsten Beyer
B.5.3	Address:
B.5.3.1	Street Address	Augustenburger Platz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13353
B.5.3.4	Country	Germany
B.5.4	Telephone number	4930450659054
B.5.5	Fax number	4930450559951
B.5.6	E-mail	kirsten.beyer@charite.de

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	Infectokrupp® Inhal
D.2.1.1.2	Name of the Marketing Authorisation holder	INFECTOPHARM Arzneimittel und Consilium 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	Inhalation vapour, liquid
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	epinephrine
D.3.9.1	CAS number	51-43-4
D.3.9.3	Other descriptive name	L-EPINEPHRINE HYDROGEN TARTRATE
D.3.9.4	EV Substance Code	SUB72751
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	6 to 8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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	Comparator
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	Fastjekt® Junior
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDA Pharma GmbH & Co. KG
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	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	epinephrine
D.3.9.1	CAS number	3198-07-0
D.3.9.3	Other descriptive name	ETHYLNOREPINEPHRINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB13769MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0,15 to 0,3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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

Food allergy

Nahrungsmittelallergie

E.1.1.1

Medical condition in easily understood language

Food allergy

Nahrungsmittelallergie

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Mean change of anaphylaxis symptom scores (ASC, considered weighted symptoms of the organ systems (CASC) and if necessary use of an additional medicinal anaphylaxis therapy, DASC) evaluated from baseline to endpoint after 20 minutes (for the FA (Full-Analysis-) population)

Mittlere Änderung des Anaphylaxie-Symptom-Scores (ASC, berücksichtigt gewichtet die Symptome an den Organsystemen (CASC) sowie die ggf. erforderliche Anwendung einer zusätzlichen arzneilichen Anaphylaxie-Therapie, DASC) von Baseline bis zum Endpunkt nach 20 Minuten (ausgewertet für die FA-(Full-Analysis-) Population).

E.2.2

Secondary objectives of the trial

• epinephrine plasma levels 10 minutes after the start of study medication application and changes to baseline levels determination at t1a
• ASC and change from baseline (T1b) to all acquisition times (5, 10, 15, 20, 25, 30, 40, 50, 60 min.)
• ASC single core values, sum of clinical score values (CASC), sum of additional anaphylaxis therapy score values (DASC) and change from baseline (T1b) to all detection times
• Application of an additional drug therapy for the treatment of anaphylactic reactions
• AEs, SAEs and side effects

• Epinephrin-Plasmaspiegel 10 Minuten nach Beginn der Prüfmedikationsapplikation und Veränderung zur Baseline-Spiegelbestimmung bei t1a
• ASC und Veränderung zur Baseline (t1b) zu allen Erfassungszeitpunkten (5, 10, 15, 20, 25, 30, 40, 50, 60 min.)
• ASC-Einzelscorewerte, Summe der klinischen Scorewerte (CASC), Summe der zusätzlichen Anaphylaxie-Therapie-Scorewerte (DASC) und Veränderung zur Baseline (t1b) zu allen Erfassungszeitpunkten
• Anwendung einer zusätzlichen medikamentösen Therapie zur Behandlung der anaphylaktischen Reaktion
• UEs, SUEs und Nebenwirkungen

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(Inclusion criteria) "run-in" phase:
• Written consent of the parents in the study participation
• Age: 1 to 6 years of age
• Weight 7,5 to 30kg
• Planned inpatient admission under a medically indicated oral food challenge

(Inclusion criteria) "Treatment" phase:
• anaphylactic reaction during the oral food challenges, defined by:
(1) at least two affected organ systems (skin, gastrointestinal tract, respiratory tract, and / or heart / circulatory system) with an anaphylaxis symptom score of at least 5 points or
(2) peripheral or central airway obstruction or
o (3) drop of blood pressure (reduced systolic blood pressure 70 mm Hg plus 2 x age in years or drop of blood pressure:> 30% drop in systolic blood pressure value)

(Einschlusskriterien) „Run-in“-Phase:
• Schriftliche Einwilligung der Eltern in die Studienteilnahme
• Alter: 1 bis 6 Lebensjahre
• Gewicht 7,5 bis 30 kg
• Geplante stationäre Aufnahme im Rahmen einer medizinisch indizierten oralen Nahrungsmittelprovokation

(Einschluss-kriterien) „Treatment“-Phase:
• Therapiebedürftige anaphylaktische Reaktion im Rahmen der oralen Nahrungsmittelprovokationen, definiert durch:
o (1.) mindestens zwei betroffene Organsysteme (Haut, Gastrointestinal-Trakt, Atemwege, und/oder Herz/Kreislauf) mit einem Anaphylaxie-Symptom-Score von mindestens 5 Punkten oder
o (2.) periphere oder zentrale Atemwegsobstruktion oder
o (3.) Blutdruckabfall (Reduzierter systolischer Blutdruck 70 mm Hg plus 2 x Alter in Jahren oder Blutdruckabfall: >30% Abfall des systolischen Blutdruckwertes)

E.4

Principal exclusion criteria

- Acute feverish infection
- Known clinically significant cardiovascular disease such as angina pectoris, obstructive cardiomyopathy, arrhythmia, diseases of the coronary arteries, the heart muscle, sclerotic vascular changes, cor-pulmonale or atherosclerosis and clinically relevant hypertension
- known clinically relevant diabetes
- Known hypercalcemia or hypokalemia
- Known hyperthyroidism
- Familiar pheochromocytoma
- Known severe renal dysfunction or bladder dysfunction with urinary retention
- familiar narrow-angle glaucoma
- Known other serious diseases which not allows a participation in the clinical trial in the opinion of the investigator
- known presence of other contraindication according to SmPC(s) of the investigational medicinal product used (Infectokrupp® Inhal, Fastjekt® Junior), in particular if a contraindicated concomitant medication is used (see below)
- A history of hypersensitivity reactions to ingredients of the IMP used, in particular sodium metabisulphite
- Preceding participate in this study
- Participation in a clinical trial during the last 30 days
- inability of the parents to understand the study instructions; obvious unreliability or lack of cooperation of the parents
- application / taking one of the following contraindicated concomitant medications or therapies:
- beta blockers or alpha-blockers
- digitalis, Chinidine, halothane or cyclopropane
- levodopa, parasympatholytics (e.g. atropine)
- sympathomimetic, e.g. orciprenaline
- tri- and tetracyclic antidepressants
- Monoamine oxidase inhibitors
- guanethidine, L-thyroxine
- oxytocin, ornipressin, carbazochrome
- insulin, antidiabetics
- reserpine, mecamylamine
- Certain antihistamines: diphenhydramine, chlorpheniramine
- pharmaceuticals which causes potassium loss: e.g. diuretics which reduces potassium: aminophylline or theophylline
- pharmaceutical preparations containing alcohol
- antihistamines or leukotriene receptor antagonist during the last 72 hours
- Long-acting beta-2-agonists, or theophylline during the past 48 hours
- unwilling to consent to saving and propagation of pseudonymised medical data for study reasons
- Subjects who are legally detained in an official institution
- Subjects and their parents who are in a dependent relationship with the Investigator or the Sponsor

 Akuter fieberhafter Infekt
 Bekannte klinisch relevante Herz- und Kreislauf-Erkrankungen wie Angina pectoris, obstruktive Kardiomyopathie, Herzrhythmusstörungen, Erkrankungen der Herzkranzgefäße, des Herzmuskels, sklerotischen Gefäßveränderungen, Cor pulmonale oder Atherosklerose und klinisch relevante Hypertonie
 Bekannter klinisch relevanter Diabetes
 Bekannte Hyperkalzämie bzw. Hypokaliämie
 Bekannte Hyperthyreose
 Bekanntes Phäochromozytom
 Bekannte schwere Nierenfunktionsstörungen oder Blasenentleerungsstörungen mit Restharnbildung
 Bekanntes Engwinkelglaukom
 Bekannte sonstige schwerwiegende Erkrankungen, die einer Teilnahme nach Einschätzung des Prüfarztes entgegen stehen
 Bekanntes Vorliegen einer sonstigen Kontraindikation gemäß Fachinformation(en) der verwendeten Prüfmedikation (Infectokrupp® Inhal, Fastjekt® Junior), insbesondere Einnahme einer kontraindizierten Begleitmedikation (s.u.)
 Anamnestisch bekannte Überempfindlichkeitsreaktionen gegen Bestandteile einer der verwendeten Prüfmedikationen, insbesondere gegen Natriummetabisulfit
 Vorausgegangene Teilnahme an dieser Studie
 Teilnahme an einer klinischen Prüfung in den letzten 30 Tagen
 Unfähigkeit der Eltern, die Studienanweisungen zu verstehen; offensichtliche Unzuverlässigkeit oder fehlende Kooperationsbereitschaft der Eltern
 Anwendung/Einnahme einer der folgenden kontraindizierten Begleitmedikationen oder –therapien:
 Beta-Blocker oder Alpharezeptor-Blocker
 Digitalisglykoside, Chinidine, Halothan oder Cyclopropan
 Levodopa, Parasympatholytika (z. B. Atropin)
 Sympathomimetika, z. B. Orciprenalin
 Tri- und tetrazyklische Antidepressiva
 Monoaminooxidasehemmer
 Guanethidin, L-Thyroxin
 Oxytocin, Ornipressin, Carbazochrom
 Insulin, Antidiabetika
 Reserpin, Mecamylamin
 Bestimmte Antihistaminika: Diphenhydramin, Chlorphenamin
 Präparate, die zu Kaliumverlust führen, z. B. Kaliumentziehende Diuretika, Aminophyllin oder Theophyllin
 Alkoholhaltige Präparate
 Antihistaminika oder Leukotrienrezeptorantagonisten während der letzten 72 Stunden
 Langwirksame Beta-2-Mimetika oder Theophyllin während der letzten 48 Stunden
 Fehlende Bereitschaft zur Speicherung und Weitergabe pseudonymisierter Krankheitsdaten im Rahmen der klinischen Prüfung
 Unterbringung in einer Anstalt auf gerichtliche oder behördliche Anordnung
 Patienten und Eltern, die vom Prüfer, dem Sponsor oder der Prüfstelle abhängig sind

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint
Mean change of anaphylaxis symptom scores (ASC, considered weighted symptoms of the organ systems (CASC) and any necessary use of an additional medicinal anaphylaxis therapy, DASC) evaluated from baseline to endpoint after 20 minutes (for the FA (Full-Analysis-) population).

Primäre Zielparameter
Mittlere Änderung des Anaphylaxie-Symptom-Scores (ASC, berücksichtigt gewichtet die Symptome an den Organsystemen (CASC) sowie die ggf. erforderliche Anwendung einer zusätzlichen arzneilichen Anaphylaxie-Therapie, DASC) von Baseline bis zum Endpunkt nach 20 Minuten (ausgewertet für die FA-(Full-Analysis-) Population).

E.5.1.1

Timepoint(s) of evaluation of this end point

after 20 minutes

nach 20 Minuten

E.5.2

Secondary end point(s)

• epinephrine plasma levels 10 minutes after the application of the IMP and changes to baseline levels determination in t1a
• ASC and change from baseline (T1b) to all detection times (5, 10, 15, 20, 25, 30, 40, 50, 60 min.)
• ASC single core values sum of clinical score values (CASC), sum of additional anaphylaxis therapy score values (DASC) and change from baseline (T1b) to all detection times
• Application of an additional drug therapy for the treatment of anaphylactic reactions
• AEs, SAEs and side effects

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

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)

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

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

Yes

E.8.2.3.1

Comparator description

Fastjekt junior

E.8.2.4

Number of treatment arms in the trial

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

LPLV

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

Yes

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

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

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children

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)

After completion of all planned study procedures the subjects will be regularly treated in our clinic by trained clinicians.

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

2016-05-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-10

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials