Clinical Trials Register

Summary
EudraCT Number:	2011-001952-12
Sponsor's Protocol Code Number:	CAFQ056B2279
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-03-06
Trial results	View 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

2011-001952-12

A.3

Full title of the trial

An open-label study to evaluate the long-term safety, tolerability and efficacy of AFQ056 in adult patients with Fragile X Syndrome

Studio in aperto per valutare la sicurezza, la tollerabilita' e l efficacia a lungo termine di AFQ056 in pazienti adulti con Sindrome dell X Fragile

A.3.1

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

Long-term, Safety, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome

Studio di tollerabilita', efficacia e sicurezza a lungo termine di AFQ056 in pazienti adulti con Sindrome dell'X Fragile

A.4.1

Sponsor's protocol code number

CAFQ056B2279

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01348087

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	NOVARTIS FARMA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farma
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39 02 96541
B.5.5	Fax number	+39 02 9659066
B.5.6	E-mail	info.studiclinici@novartis.com

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	No
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	NA
D.3.2	Product code	AFQ056
D.3.4	Pharmaceutical form	Capsule, hard
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	NA
D.3.9.1	CAS number	543906-09-8
D.3.9.2	Current sponsor code	AFQ056
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
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	25
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	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	No
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	NA
D.3.2	Product code	AFQ056
D.3.4	Pharmaceutical form	Capsule, hard
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	NA
D.3.9.1	CAS number	543906-09-8
D.3.9.2	Current sponsor code	AFQ056
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	NA
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	100
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

Fragile X Syndrome

Sindrome dell'X Fragile

E.1.1.1

Medical condition in easily understood language

Fragile X Syndrome

Sindrome dell'X Fragile

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10017324
E.1.2	Term	Fragile X syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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

To evaluate the safety and tolerability of AFQ056 in adult patients with FXS as assessed by: • Incidence and severity of adverse events and serious adverse events • Changes in vital signs, laboratory assessments, and ECGs

Valutare la sicurezza e tollerabilità di AFQ056 in pazienti adulti con FXS attraverso:
• Incidenza e severità degli eventi avversi e degli eventi avversi seri
• Variazioni dei segni vitali, esami di laboratorio e ECG

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of AFQ056 treatment in both Fully Methylated and Partially Methylated patients with FXS as assessed by: • Change from baseline in the Aberrant Behavior Checklist – Community edition (ABC-C) total score and subscale scores • Rating of global improvement of symptoms in Fragile X patients using the Clinical Global Impression - Improvement (CGI-I) scale. • Change from baseline in the Repetitive Behavior Symptom – Research version (RBS) total score and subscale scores

Valutare l’efficacia del trattamento con AFQ056 nei pazienti con FXS FM (Fully Methylated) e PM
(Partially Methylated) mediante:
• Variazioni rispetto al basale nel punteggio totale e nei punteggi delle sottoscale della “Aberrant
Behavior Checklist – Community edition (ABC-C)”
• Valutazione del miglioramento globale dei sintomi nei pazienti con FXS impiegando la scala
“Clinical Global Impression - Improvement (CGI-I)”
• Variazione rispetto al basale nel punteggio totale e nei punteggi delle sottoscale della “Repetitive
Behavior Symptom – Research version (RBS)”
Per maggiori dettagli consultare il capitolo 2 del protocollo originale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Must have been enrolled in Studies CAFQ056A2204 or CAFQ056A2212 - Has a caregiver who spends, on average, at least 6 hours per day with the patient , who is willing to and capable of supervising treatment, providing input into efficacy and safety assessments, and accompanying the patient to study visits. Other protocol-defined inclusion criteria may apply

Pazienti del gruppo 1:
• Devono aver completato lo studio principale CAFQ056A2212 entro una settimana
dall’arruolamento nello studio in aperto..
• Uomini e donne di età compresa tra 18 e 46 anni, compresi; le donne devono impiegare un
metodo di contraccezione accettabile in accordo con il protocollo di studio
• Devono avere un tutore legale che rimanga, in media, almeno sei ore al giorno con il paziente, e
che sia disponibile ed in grado di supervisionare il trattamento, fornendo informazioni sulle
valutazioni di efficacia e di sicurezza, e di accompagnare il paziente alle visite previste dallo
studio.
Pazienti del gruppo 2:
• Devono soddisfare una delle seguenti condizioni:
a. Avere completato lo studio CAFQ056A2204
b. Avere completato lo studio CAFQ056A2212 ma l’arruolamento nel presente studio è
stato ritardato per più di una settimana
c. Avere discontinuato prematuramente il trattamento dello studio CAFQ056A2212 a
seguito di mancata tollerabilità intolleranza alla dose del gruppo di trattamento
assegnato al paziente
• Il consenso informato deve essere ottenuto dal rappresentante legale del paziente prima di
effettuare qualsiasi procedura prevista dallo studio;
• Uomini e donne di età compresa tra 18 e 46 anni, compresi; le donne devono impiegare un
metodo di contraccezione accettabile in accordo con il protocollo di studio
Per favore ved. sinossi in italiano

E.4

Principal exclusion criteria

- Any advanced, severe or unstable disease - History of severe self-injurious behavior - History of uncontrolled seizure disorder or resistant to therapy within the past 2 years (Patients who are clinically stable under anti-convulsant therapy for the past 2 years are not excluded) - History of clinically significant allergies requiring hospitalization or non-inhaled corticosteroid therapy (asthma, anaphylaxis, etc.) - Any treatment regimen, including psychotropic and/or anticonvulsant therapy that has not been stable for ≥ 6 weeks prior to randomization - Current treatment with more than two psychoactive medications, excluding medication used specifically for seizure control - Using (or used within 6 weeks before randomization) concomitant medications that are potent inhibitors or inducers of CYP3A4 - Using glutamatergic agents (riluzole, memantine, etc.) or lithium within 6 weeks of randomization - Planning to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study Other protocol-defined exclusion criteria may apply

• Qualsiasi malattia in stadio avanzato, severa o non stabilizzata
• Storia e/o presenza di schizofrenia, malattia bipolare, psicosi, stati confusionali e/o allucinazioni
ripetute secondo i criteri DSM-IV (Diagnostic and Statistical Manual of Mental Disorders)
• Storia di comportamento suicida o considerato ad alto rischio di suicidio
• Storia di comportamento autolesionistico severo
• Storia di crisi epilettiche non controllate o resistenti alla terapia nei 2 anni precedenti (i pazienti che
sono clinicamente stabili in terapia anticonvulsivante per i anni precedenti non sono esclusi)
• Storia di allergie clinicamente significative che hanno richiesto ospedalizzazioni o terapia
corticosteroidea non inalatoria (asma, anafilassi, etc.)
• Qualsiasi regime di trattamento, con inclusione della terapia psicotropica e/o anticonvulsivante non
stabile per un periodo uguale o superiore a 6 settimane prima della randomizzazione
• Trattamento in corso con più di due farmaci psicoattivi, con l’esclusione di farmaci utlizzati
specificamente per il controllo di crisi epilettiche
• Utilizzo concomitante (o entro le 6 settimane prima della randomizzazione) di farmaci potenti
inibitori o induttori del CYP3A4
• Uso di agenti glutamatergici (riluzolo, memantina, etc.) o litio entro le 6 settimane precedenti la
randomizzazione
• Programma di iniziare o di modificare la terapia farmacologica o non farmacologica durante lo
studio.
Per maggiori dettagli consultare i paragrafi 4.1 e 4.2 del protocollo originale.

E.5 End points

E.5.1

Primary end point(s)

Evaluation of the safety and tolerability of AFQ056 in adult patients with FXS as assessed by: Incidence and severity of adverse events and serious adverse events and change in vital signs, laboratory assessments, and ECGs.

Valutazione della sicurezza e della tollerabilità di AFQ056 in pazienti adulti con la sindrome dell'X Fragile in base a : incidenza e severità degli evventi avversi e gli eventi avversi seri, cambiamenti : segni vitali, valori di laboratorio e dati degli ECGs.

E.5.1.1

Timepoint(s) of evaluation of this end point

At multiple visits: weekly during first month and monthly afterwards Time Frame: 9 months

Tempi: 9 mesi

E.5.2

Secondary end point(s)

- Aberrant Behavour Checklist - Community Edition (ABC-C): Total score and subscales - Clinical Global Impression - Improvement (CGI-I) scale - Repetitive Behaviour Symptom-Research version (RBS-R) - total score and subscale scores

E.5.2.1

Timepoint(s) of evaluation of this end point

- ABC-C: Week 4, week 12, week 24, week 36 - CGI - I: Week 4, week 12, week 24, 36 week - RBS: Week 4, week 36 Time frame: 9 months for each

Tempi : 9 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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

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