Clinical Trials Register

Summary
EudraCT Number:	2019-002618-38
Sponsor's Protocol Code Number:	721
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:	2021-06-01
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

2019-002618-38

A.3

Full title of the trial

Clinical trial - phase II - to test safety and efficay of Etravirine's treatment in Friedreich Ataxia's patients

Studio clinico di fase II per testare sicurezza ed efficacia del trattamento con Etravirina in pazienti con Atassia di Friedreich

A.3.1

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

Clinical trial - phase II - to test safety and efficay of Etravirine's treatment in Friedreich

Studio clinico di fase II per testare sicurezza ed efficacia del trattamento con Etravirina in pazienti con Atassia di Friedreich

A.3.2

Name or abbreviated title of the trial where available

FAEST

A.4.1

Sponsor's protocol code number

721

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	ASSOCIAZIONE "LA NOSTRA FAMIGLIA" - SEZIONE SCIENTIFICA I.R.C.C.S. "E.MEDEA"
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	aCHAF Association
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Associazione italiana per la lotta alle sindromi atassiche (A.I.S.A. Onlus)
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Babel Family
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Associazione "OGNI GIORNO" - per Emma onlus
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Associazione "Per il Sorriso di Ilaria-Montebruno-Onlus"
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Università di Roma “Tor Vergata”
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Associazione "Un petalo per Margherita Onlus"
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	Associazione La Nostra Famiglia
B.5.2	Functional name of contact point	Segreteria Scientifica
B.5.3	Address:
B.5.3.1	Street Address	Via Don Luigi Monza 20
B.5.3.2	Town/ city	Bosisio Parini
B.5.3.3	Post code	23892
B.5.3.4	Country	Italy
B.5.4	Telephone number	031877330
B.5.6	E-mail	medea@lanostrafamiglia.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.2.1.1.1	Trade name	INTELENCE - 200 MG - COMPRESSA -USO ORALE - FLACONE (HDPE) 60 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
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	INTELENCE
D.3.2	Product code	[J05AG04]
D.3.4	Pharmaceutical form	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	ETRAVIRINA
D.3.9.1	CAS number	269055-15-4
D.3.9.2	Current sponsor code	ETR
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	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

Friedreich's ataxia

Atassia di Friedreich

E.1.1.1

Medical condition in easily understood language

Friedreich's ataxia

Atassia di Friedreich

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10017374
E.1.2	Term	Friedreich's ataxia
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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

Test the safety of ETR treatment in patients with FRDA (two groups of patients treated with 2 different doses: 200 mg / day and 400 mg / day). The goal is to monitor all EAs that will occur during 4 months of treatment with ETR compared to EAs recorded during 4 months of observation before and 4 months after treatment.

Testare la sicurezza del trattamento con ETR in pazienti con FRDA (due gruppi di pazienti trattati con 2 dosi diverse: 200 mg/die e 400 mg/die). L’obiettivo si raggiungerà monitorando tutti gli EA che si verificheranno durante i 4 mesi di trattamento con ETR rispetto agli EA registrati durante 4 mesi di osservazione prima e 4 mesi dopo il trattamento.

E.2.2

Secondary objectives of the trial

Test the effect of treatment with ETR at 2 doses (200 mg / day or 400 mg / day) comparing, in each patient, the changes recorded with the measurements of the primary and secondary efficacy endpoints observed during the three periods of the study (treatment duration , observation before and after treatment).

Testare l’effetto del trattamento con ETR a 2 dosi (200 mg/die o 400 mg/die) confrontando, in ciascun paziente, i cambiamenti registrati con le misure di efficacia primari e secondari osservati durante i tre periodi dello studio (durata del trattamento, osservazione prima e dopo il trattamento).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• FRDA molecularly defined (expansion in at least one of the alleles of the FXN gene). • Absence of HIV infection (anti-HIV research negativity) • Ability to complete the cycle ergometer test with legs or arms to measure maximum exercise (the patient must be able to pedal at least 60 rpm without additional resistance for at least 3 minutes). • Willingness to participate in the study and sign the informed consent form. • Age range 10-40 years

• FRDA molecolarmente definiti (espansione in almeno uno degli alleli del gene FXN). • Assenza di infezione da HIV (negatività ricerca AC anti HIV) • Capacità di completare il test del cicloergometro azionato con gambe o braccia per misurare l’esercizio massimale (il paziente deve essere in grado di eseguire pedalate di almeno 60 giri/min senza resistenza aggiuntiva per almeno 3 minuti). • Volontà di partecipare allo studio e firma del modulo del consenso informato. • Range di età 10-40 anni

E.4

Principal exclusion criteria

• Pregnancy or breastfeeding in place. • Known sensitivity to the ETR or to one of its excipients. • Exposure to ETR or other experimental therapies used in FRDA (eg IFNy, erythropoietin, nicotinamide, idebenone, deferiprone, etc.). • Any previous treatments with ETR should have been interrupted at least 4 months before entering the study. • Serious medical conditions that can interfere with the absorption and distribution of the drug (liver or kidney failure, severe metabolic imbalance), major heart disease (ejection fraction <40%). • Ongoing treatment with carbamazepine, phenobarbital, phenytoin, rifampicin, rifapentine, clopidogrel, hypericum. • Positivity to the HIV test

• Gravidanza o allattamento in atto. • Sensibilità nota all’ETR oppure ad uno degli eccipienti che lo compongono. • Esposizione all’ ETR o altre terapie sperimentali utilizzati nell’ambito della FRDA (ad es. IFNy, eritropoietina, nicotinamide, idebenone, deferiprone, ecc.). • Eventuali trattamenti precedenti con ETR dovrebbero essere stati interrotti almeno 4 mesi prima dell'ingresso nello studio. • Gravi condizioni mediche che possono interferire con l'assorbimento e la distribuzione del farmaco (insufficienza epatica o renale, grave squilibrio metabolico), patologia cardiaca importante (frazione di eiezione <40%). • Trattamento in corso con carbamazepina, fenobarbital, fenitoina, rifampicina, rifapentina, clopidogrel, iperico. • Positività al test per HIV

E.5 End points

E.5.1

Primary end point(s)

Evaluate the safety of the drug through the following assessment and consideration: • Record the presence, number and type of non severe EAs, including the results of blood and urinary tests. • Record the presence or absence of severe adverse events (SAEs) related to the administration of the investigational drug. • The study will be considered satisfactory in the absence of any SAE due to the drug.

Valutare la sicurezza del farmaco tramite la seguente valutazione e considerazione: • Registrare la presenza, il numero e la tipologia degli EA non severi, compresi anche gli esiti degli esami ematici e urinari. • Registrare la presenza o assenza degli eventi avversi severi (SAE) correlati alla somministrazione del farmaco sperimentale. • Lo studio sarà ritenuto soddisfacente nel caso di assenza di qualsiasi SAE dovuto al farmaco.

E.5.1.1

Timepoint(s) of evaluation of this end point

8 months: 4 months of treatment and 4 months of post treatment

8 mesi: 4 mesi di trattamento e 4 mesi post

E.5.2

Secondary end point(s)

Changes in Quality of life (QoL) as measured with Short form 36 (SF36) and WHO-DAS 2.0 at T-4, T0, T4, T8; Efficacy of the Etravirine treatment in improving the peak VO2 measured by incremental exercise test; Changes in Total SARA score; Variations in teh interventricular wall thickness (EcoCG and EKG); Changes in the level of frataxin in PBMC measured at T-4, T0, T4 and T8

cambiamenti della Qualità di vita (QoL) e misurati tramite: Short Form 36 (SF-36) e WHO-DAS 2.0. misurate a T-4, T0, T4, T8; Efficacia del trattamento con Etravirina nel migliorare la VO2 di picco misurata con esercizio incrementale; cambiamenti nel punteggio totale SARA; Variazioni dello spessore della parete ventricolare (EcoCG/ECG) misurato a T-4, T0, T4, T8.; modificazioni del contenuto di fratassina nelle cellule polimorfonucleate del sangue periferico (PBMC) misurate a T-4, T0, T4, T8

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months: T-4. T0, T4, T8; 12 months: 4 months of observation pre.treatment with exercise test at study entry (T-4) and 4 months later just before starting the treatment (T0), 4 months of treatment with exercise test at T0 and T4 and 4 months of post treatment observation with exercise test at T4 and T8; 12 months: 4 months of observation pre.treatment with evaluation at study entry (T-4) and 4 months later just before starting the treatment (T0), 4 months of treatment with evaluation at T0 and T4 and 4 months of post treatment observation with evaluation at T4 and T8; 12 months: T-4, T0, T4, T8; 12 months: T-4, T0, T4, T8

12 months: T-4, T0. T4, T8; 12 mesi: 4 mesi di osservazione pre-trattamento con prova sa sforzo a inizio studio (T-4) e 4 mesi dopo, subito prima dell'inizio del trattamento (T0), 4 mesi di trattamento con prova da sforo a T0 e T4 e osservazione post trattamento con prova da sforzo T4 e T8; 12 mesi: 4 mesi di osservazione pre-trattamento con valutazione a inizio studio (T-4) e 4 mesi dopo, subito prima dell'inizio del trattamento (T0), 4 mesi di trattamento con valutazione a T0 e T4 e osservazione post trattamento con valutazione T4 e T8; 12 mesi: T-4, T0, T4, T8; 12 mesi: T-4, T0, T4, T8

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

Yes

E.6.5

Efficacy

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.2.4

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.8.4.1

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)

The subjects who will finish the study will receive the usual medical attention guaranteed before the study.

I soggetti che termineranno lo studio riceveranno l'usuale attenzione medica garantita precedentemente allo studio.

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

2020-03-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-25

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

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