Clinical Trials Register

Summary
EudraCT Number:	2019-004426-24
Sponsor's Protocol Code Number:	TREAT-LMNA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-15
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-004426-24

A.3

Full title of the trial

Deflazacort TREATment in LMNA related congenital muscular dystrophy: study of clinical effectiveness and search for reliable biomarkers.

Deflazacort TRATTAMENTO nella distrofia muscolare congenita correlata a LMNA: studio dell'efficacia clinica e ricerca di biomarcatori affidabili

A.3.1

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

Deflazacort TREATment in LMNA related congenital muscular dystrophy: study of clinical effectiveness and search for reliable biomarkers.

Deflazacort TRATTAMENTO nella distrofia muscolare congenita correlata a LMNA: studio dell'efficacia clinica e ricerca di biomarcatori affidabili

A.3.2

Name or abbreviated title of the trial where available

TREAT-LMNA

A.4.1

Sponsor's protocol code number

TREAT-LMNA

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	AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
B.1.3.4	Country	Italy
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	AIFA - Italian Medicines Agency
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	Azienda Ospedaliero - Universitaria Pisana
B.5.2	Functional name of contact point	U.O. Farmacologia Clinica e Farmaco
B.5.3	Address:
B.5.3.1	Street Address	Via Roma 67
B.5.3.2	Town/ city	Pisa
B.5.3.3	Post code	56126
B.5.3.4	Country	Italy
B.5.4	Telephone number	050996215
B.5.5	Fax number	050993570
B.5.6	E-mail	v.gori@ao-pisa.toscana.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	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Deflazacort
D.3.2	Product code	[Deflazacort]
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Buccal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	deflazacort
D.3.9.2	Current sponsor code	deflazacort
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	1
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	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	Lucen
D.2.1.1.2	Name of the Marketing Authorisation holder	Malesci
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Lucen
D.3.2	Product code	[-]
D.3.4	Pharmaceutical form	Gastro-resistant granules
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	esomeprazolo
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	esomeprazole
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Congenital Muscolar distrophy LMNA related

Distrofia muscolare congenita correlata a LMNA ( L-CMD)

E.1.1.1

Medical condition in easily understood language

Congenital muscolar distrophy coused by lamina gene mutation

distrofia muscolare congenita causata da mutazione del gene lamina

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003718
E.1.2	Term	Atrophy skeletal muscle
E.1.2	System Organ Class	100000004859

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

The primary objectives of the study will be:
1. Evaluation of the effect of therapy with Deflazacort drops 0.9 mg / kg / day on clinical outcome and secretoma in adult and pediatric patients with L-CMD.
2. Evaluation of the safety and tolerability of the treatment with Deflazacort drops 0.9 mg / kg / day

Gli obiettivi primari dello studio saranno:
1. Valutazione dell'effetto della terapia con Deflazacort gocce 0,9 mg / kg / die sull'esito clinico e sul secretoma in pazienti adulti e pediatrici affetti da L-CMD.
2. Valutazione della sicurezza e della tollerabilità del trattamento con Deflazacort gocce 0,9 mg / kg / die

E.2.2

Secondary objectives of the trial

The secondary objective will be to study in vitro whether LCMD specific secreted molecules influence myogenic differentiation and fibrosis in normal human myoblasts in culture, thus validating these molecules as biomarkers in L-CMD.

L'obiettivo secondario sarà quello di studiare in vitro se le molecole secrete specifiche della LCMD influenzano la differenziazione miogenica e la fibrosi nei mioblasti normali umani in coltura, convalidando così queste molecole come biomarcatori nell'L-CMD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Corticosteroid-naive patients, aged between 3 and 40 years of both sexes and of Caucasian origin, with clinical and genetic diagnosis of L-CMD or EDMD2 with an onset age before 5 years.
• Patients will be eligible if at the time of recruitment they are able to provide reproducible measurements of forced vital capacity (FVC) (variability <15% between two repeated measures of FVC).
• Signing of informed consent by the patient, in the case of an adult individual, or by the parents / legal guardian, in the case of an individual under the age of 18.

Then, patients will be divided into two subgroups based on clinical characteristics:
i) subgroup 1: patients who maintain the following abilities:
-to walk for at least 50 meters at 6 minutes of walking test (6MWT)
- get up from the floor, with or without support.
ii) subgroup 2: patients with loss of gait or more severe motor impairment who do not maintain the abilities described above.

• Pazienti naïve ai corticosteroidi, di età compresa tra 3 e 40 anni di entrambi i sessi e di origini caucasiche, con diagnosi clinica e genetica di L-CMD o EDMD2 con età insorgente prima dei 5 anni.
• I pazienti saranno ammissibili se al momento del reclutamento sono in grado di fornire misurazioni riproducibili della capacità vitale forzata (FVC) (variabilità <15% tra due misure ripetute di FVC).
• Sottoscrizione del consenso informato da parte del paziente, in caso di individuo adulto, o dei genitori/tutore legale, in caso di individuo minorenne.

Quindi, i pazienti saranno suddivisi in due sottogruppi in base alle caratteristiche cliniche:
i) sottogruppo 1: pazienti che mantengono le seguenti capacità:
-per camminare per almeno 50 metri a 6 minuti di test di camminata (6MWT)
-alzarsi dal pavimento, con o senza supporto.
ii) sottogruppo 2: pazienti con perdita di deambulazione o compromissione motoria più grave che non mantengono le capacità sopra descritte.

E.4

Principal exclusion criteria

Exclusion criteria
• Hypersensitivity to the active substance or to any of the excipients
• Chronic therapy with corticosteroids or immunosuppressive drugs
• Diabetes mellitus or other comorbidities which strongly contraindicate the use of corticosteroids
• Pregnancy and breastfeeding.

Criteri di esclusione
• Ipersensibilità al principio attivo o ad uno qualsiasi degli eccipienti
• Terapia cronica con corticosteroidi o farmaci immunosoppressori
• Diabete mellito o altre comorbidità che controindicano fortemente l'uso di corticosteroidi
• Gravidanza e allattamento.

E.5 End points

E.5.1

Primary end point(s)

1. Safety evaluation of the administration of Deflazacort drops (0.9mg / kg / day)

2. Evaluation of the effects of treatment with Deflazacort drops (0.9mg / kg / day in relation to the change of clinical parameters at each treatment time and follow up (T0-T6-T12-T15-T18).
For subgroup 1, the primary clinical outcome variable will be chosen as a three-dimensional (multivariate) outcome consisting of the following three components:
• relaxation time
• FVC
• motor measurement (MFM)

For subgroup 2, the primary clinical outcome variable will be:
• FVC
• motor measurement (MFM)

1. Valutazione di sicurezza della somministrazione di Deflazacort gocce (0.9mg/kg/die)

2. Valutazione degli effetti del trattamento con Deflazacort gocce (0.9mg/kg/die in relazione al cambiamento di parametri clinici ad ogni tempo di trattamento e follow up (T0-T6-T12-T15-T18).
Per il sottogruppo 1, la variabile di esito clinico primario sarà scelta come esito tridimensionale (multivariato) costituito dai seguenti tre componenti:
• tempo di distensione
• FVC
• misurazione motoria ( MFM)

Per il sottogruppo 2, la variabile di esito clinico primario sarà:
• FVC
• misurazione motoria (MFM)

E.5.1.1

Timepoint(s) of evaluation of this end point

18 mesi

E.5.2

Secondary end point(s)

Secondary outcome variables will include the following continuous variables, calculated on average for all post-baseline follow-up visits:
Time to run / walk 10 m (subgroup 1);
• distance traveled in 6 minutes (subgroup 1);
• range of motion in the ankle, elbow and knee joints (subgroup 1 and 2);
• cardiac function (measured by transthoracic echocardiography and 12-lead ECG) (subgroup 1 and 2);

Le variabili di risultato secondarie includeranno le seguenti variabili continue, calcolate in media per tutte le visite di follow-up post-basale:
• tempo di correre / camminare 10 m (sottogruppo 1);
• distanza percorsa in 6 minuti (sottogruppo 1);
• gamma di movimento nelle articolazioni della caviglia, del gomito e del ginocchio (sottogruppo 1 e 2);
• funzione cardiaca (misurata mediante ecocardiografia transtoracica ed ECG a 12 derivazioni) (sottogruppo 1 e 2);

E.5.2.1

Timepoint(s) of evaluation of this end point

18 mesi

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

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

Yes

E.6.13.1

Other scope of the trial description

specific biomarkers

ricerca biomarcatori

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

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)

Yes

E.8.2.2

Placebo

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

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

Information not present in EudraCT

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

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

Yes

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

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)

Fr each patient, the study will be completed at the end of treatmentand of follow up

Per ogni paziente lo studio sarà completato alla fine del trattamento e del follow up

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

2020-07-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-11

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

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