Clinical Trials Register

Summary
EudraCT Number:	2012-002692-34
Sponsor's Protocol Code Number:	MitoFibrateCT1-2012
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-02-26
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

Austria - BASG

A.2

EudraCT number

2012-002692-34

A.3

Full title of the trial

Clinical study for the assessment of safety and efficacy of Bezafibrate as a drug therapy for patients with mitochondrial myopathies

Klinische Studie zum Nachweis der Sicherheit und Wirksamkeit von
Bezafibrat als Arzneimitteltherapie für Patienten mit mitochondrialen Muskelerkrankungen

A.3.1

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

Clinical study for the assessment of safety and efficacy of Bezafibrate as a drug therapy for patients suffering from an inborn muscular dysfunction characterized by intramuscular lack of energy supply

Klinische Studie zum Nachweis der Sicherheit und Wirksamkeit von
Bezafibrat als Arzneimitteltherapie für Patienten mit angeborener Muskelerkrankung, die zu einer gestörten Energiebereitstellung
der Muskulatur führt

A.3.2

Name or abbreviated title of the trial where available

MitoFibrate CT1

A.4.1

Sponsor's protocol code number

MitoFibrateCT1-2012

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	Univ.-Klinik für Kinder- und Jugendheilkunde
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	Univ.-Klinik für Kinder- und Jugendheilkunde
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	Institut für angeborene Stoffwechselerkrankungen
B.5.2	Functional name of contact point	Clinical trial information
B.5.3	Address:
B.5.3.1	Street Address	Strubergasse 21
B.5.3.2	Town/ city	Salzburg
B.5.3.3	Post code	5020
B.5.3.4	Country	Austria
B.5.4	Telephone number	00436624420021224
B.5.6	E-mail	florian.lagler@pmu.ac.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	Bezastad
D.2.1.1.2	Name of the Marketing Authorisation holder	STADA Arzneimittel GmbH, Wien
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	Bezastad
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEZAFIBRATE
D.3.9.1	CAS number	41859-67-0
D.3.9.3	Other descriptive name	2-[4-[2-(4-Chlorobenzamido)ethyl]phenoxy]isobutyric Acid
D.3.9.4	EV Substance Code	SUB05810MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

mitochondrial disorder

Genetisch bedingte mitochondriale Muskelerkrankungen

E.1.1.1

Medical condition in easily understood language

Inborn mitochondrial diseases leading to an abberant energy supply in muscular tissue severly affecting muscular performance and sometimes leading to psycho-mental disability and breathing failure

Genetische mitochondriale Erkrankung,die zu einer gestörten intramuskulären Energiebereitstellung führt. Folgen: Leistungsintoleranz bis zu psychomentaler Behinderung und Versagen der Atemmuskulatur

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Recent findings derived from animal and cell culture studies demonstrate an upregulation of synthesis and activity of mitochondrial enzymes under bezafibrat and thus point to a beneficial effect of this substance for the therapy of mitochondrial myopathies (H. Tyynismaa et al. 2010, T. Wenz 2008 und 2010). This findings are further substantiated by clinical observations in course of compassionate use of Bezafibrat for patinets with mitochondrial myopathies at the centres planned to participate in this trial (Reutlingen, München, Salzburg, Innsbruck). The main objective of the trial is therefore the systematic evaluation of efficacy and safety of Bezafibrat as a therapeutic option for patients with mitochondrial myopathies.

Aktuelle Ergebnisse von Studien mit Tiermodellen und Patientenzelllinien weisen jedoch darauf hin, dass das Arzneimittel Bezafibrat zu einer vermehrte Synthese und Aktivierung von mitochondrialen Enzymen führt und so eine positive Wirkung bei mitochondrialen Muskelerkrankungen erzielt werden könnte (H. Tyynismaa et al. 2010, T. Wenz 2008 und 2010). Einzelne individuelle Heilversuche in den beteiligten Zentren(Reutlingen, München, Salzburg,Innsbruck) und anderen Zentren bekräftigen den Eindruck dass dies therapeutisch genutzt werden kann.Im Rahmen der geplanten klinischen Studie sollen die Wirksamkeit und Sicherheit von Bezafibrat in der Behandlung von mitochondrialen Muskelerkrankungen systematisch evaluiert werden. Nur so kann rational beurteilt werden, ob sich die erhoffte Wirksamkeit bestätigt und ob unter Abwägung relevanter Risiken eine generelle Therapieempfehlung gerechtfertigt ist.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Ability to walk
Age: 2-50 years
confirmed Complex-I-defect or PDHc-defect
ability to cope with the requirements for study participation

Gehfähigkeit
Patienten im Alter von 2-50 Jahre mit nachgewiesenem Complex-I-Defekt oder PDHc-Defekt
Patienten/Patienteneltern die in der Lage sind den Anforderungen der Studienteilnahme gerecht zu werden

E.4

Principal exclusion criteria

previously known intolerance or other contra-indications for bezafibrat

Patienten mit bekannter Unverträglichkeit oder anderer Kontraindikationen gegen die Einnahme von Bezafibrat

E.5 End points

E.5.1

Primary end point(s)

time intervall until pre-defined manifestation of disease progression measured by walking-distance in a 6-minutes-walking test
disease progression is defined as a decline of >20% in performance

Primärer Studienendpunkt ist die Zeit bis zum Auftreten einer definierten Krankheitsprogredienz gemessen an:
Gehstrecke im 6-Minuten-Gehtest
Krankheitsprogredienz entspricht per definitionem einer Verschlechterung im Gehtest um >20%

E.5.1.1

Timepoint(s) of evaluation of this end point

The subjective disease progression is measured every 4 weeks by the patients or their parents by Newcastle Scale Section 4. Once the score points to a disease progression, patients visit the study site where the primary endpoint is evaluated. Elsewise, the primary endpoint is routinely evaluated 3 and 6 months post randomization. A decline of >20% in the 6-minutes-walking test leads to termination of study participation. Elsewise, termination is routinely scheduled at study visit 6 months post randomization.

alle 4 Wochen wird die subjektive Krankheitsprogredienz durch den Patienten oder dessen Eltern mittels Newcastle Scale Section 4 erhoben. Ergibt sich Hinweis auf Progredienz, so erfolgt außerdordentliche Visite und Evaluierung des Endpunkts. Andernfalls erfolgt die Bewertung des Endpunkts 3 Monate sowie 6 Monate nach der Randomisierung. Eine Verschlechterung um 20% des 6-Minuten-Gehtests führt zur Beendigung der Studienteilnahme. Allenfalls endet die Teilnahme bei der 6 Monats Visite ab Randomisierung.

E.5.2

Secondary end point(s)

subjective disease progression: Newcastle Paediatric Mitochondrial Disease Rating Scale
function of the autonomous nervous sytem: ANS-test

Subjektive Krankheitsprogredienz: Newcastle Paediatric Mitochondrial Disease Rating Scale
Autonome Nervensystem-Funktion: ANS-Testbatterie

E.5.2.1

Timepoint(s) of evaluation of this end point

Newcastle Paediatric Mitochondrial Disease Rating Scale: every 4 weeks
ANS-Test: every 3 months

Newcastle Paediatric Mitochondrial Disease Rating Scale: alle 4 Wochen
ANS-Testbatterie: alle 3 Monate während der 9 monatigen Gesamtdauer

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

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

Yes

E.8.1.7.1

Other trial design description

„randomized withdrawal“-Studie mit einer Parallelgruppenphase nach einer offenen Phase

„randomized withdrawal“-study with an open phase followed by a parallel-group phase

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

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

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)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children

Kinder

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 the subject has ended the participation in the trial bezafibrate therapy can be continued on compassionate-use level.

Die Studienteilnehmer können nach Beendigung der Studienteilnahme weiterhin auf Wunsch die Bezafibrat -Therapie auf Basis eines individuellen Heilversuchs fortführen

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

2013-05-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-26

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