Clinical Trials Register

Summary
EudraCT Number:	2020-000439-32
Sponsor's Protocol Code Number:	NW-3509/015/II/2019
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:	2020-10-21
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-000439-32

A.3

Full title of the trial

An open-label, multi-center, extension study to evaluate the long-term safety, tolerability and preliminary efficacy of Evenamide as add-on treatment in patients with treatment-resistant schizophrenia (TRS) not responding adequately to their current antipsychotic medication.

Studio di estensione in aperto, multicentrico per valutare sicurezza, tollerabilità ed efficacia preliminare a lungo termine di evenamide come terapia aggiuntiva in pazienti affetti da schizofrenia resistente al trattamento (TRS) che non rispondono adeguatamente al farmaco antipsicotico attualmente in corso

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

NW-3509/015/II/2019

A.4.1

Sponsor's protocol code number

NW-3509/015/II/2019

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	NEWRON PHARMACEUTICALS SPA
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharmaceutical Development and services S.r.l.
B.5.2	Functional name of contact point	CRO
B.5.3	Address:
B.5.3.1	Street Address	Via dei Pratoni 16
B.5.3.2	Town/ city	Scandicci
B.5.3.3	Post code	50018
B.5.3.4	Country	Italy
B.5.4	Telephone number	0557224179
B.5.5	Fax number	0557227014
B.5.6	E-mail	edimartino@pharmades.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	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	Evenamide
D.3.2	Product code	[NW-3509]
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.3.9.1	CAS number	1092977-61-1
D.3.9.2	Current sponsor code	NW-3509
D.3.9.4	EV Substance Code	PRD7161317
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	7500
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	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	Evenamide
D.3.2	Product code	[NE-3509]
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.3.9.1	CAS number	1092977-61-1
D.3.9.2	Current sponsor code	NW-3509
D.3.9.4	EV Substance Code	PRD7161318
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	15
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: 3
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	Evenamide
D.3.2	Product code	[NW-3509]
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.3.9.1	CAS number	1092977-61-1
D.3.9.2	Current sponsor code	NW-3509
D.3.9.4	EV Substance Code	PRD7161319
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	30
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

Schizophrenia not responding adequately to current antipsychotic treatment

Schizofrenia resistente al trattamento con una dose terapeutica stabile di un farmaco antipsicotico

E.1.1.1

Medical condition in easily understood language

Treatment-resistant schizophrenia (TRS)

Schizofrenia trattamento-resistente (TRS)

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

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	10072913
E.1.2	Term	Treatment-resistant schizophrenia
E.1.2	System Organ Class	100000004873

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 long-term safety and tolerability of evenamide given orally in patients with treatment-resistant schizophrenia (TRS) not responding adequately to their current antipsychotic medication.

Valutare sicurezza e tollerabilità a lungo termine di evenamide somministrata per via orale in soggetti affetti da schizofrenia resistente al trattamento che non rispondono adeguatamente al corrente farmaco antipsicotico assunto.

E.2.2

Secondary objectives of the trial

To evaluate preliminary long-term efficacy of evenamide, based on symptoms of schizophrenia, as assessed by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression - Change from baseline (CGI-C) and Severity of illness (CGI-S); to determine the long-term effect of evenamide on daily functioning, based on changes on the Strauss-Carpenter Level of Functioning (LOF) scale.

Valutare l'efficacia preliminare a lungo termine di evenamide, in base ai sintomi della schizofrenia, valutata mediante la Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression - Change from baseline (CGI-C) e Severity of illness (CGI-S); determinare l'effetto a lungo termine di evenamide sulla Scala del livello funzionale, in base al cambiamento del punteggio sulla scala LOF (Strauss-Carpenter Level of Functioning Scale).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet the following inclusion criteria to be eligible for enrollment into the study:
1. Patient completed 6 weeks of treatment in Study 014.
2. Patient has provided written informed consent for this extension study.
3. If female, patient is not of childbearing potential, pregnant or breastfeeding. For inclusion, female patients must be post-menopausal (age 50 or older with confirmed amenorrhea for >12 months), surgically sterilized, or protected with adequate contraception (barrier method or hormonal contraceptive).

Per essere eleggibile per l'arruolamento nello studio, un paziente deve soddisfare tutti i seguenti criteri di inclusione:
1. Aver completato le 6 settimane di trattamento dello studio 014.
2. Fornire il consenso informato scritto per questo studio di estensione.
3. Se di sesso femminile, le pazienti non devono essere in età fertile, in gravidanza o in allattamento. Per poter essere incluse, le pazienti di sesso femminile devono essere in post-menopausa (età pari a 50 anni o più con amenorrea confermata per > 12 mesi), sterilizzate chirurgicamente o utilizzare un metodo contraccettivo adeguato (metodo di barriera o contraccettivo ormonale) e seguire le istruzioni del medico curante.

E.4

Principal exclusion criteria

The presence of any of the following will exclude a patient from study enrollment:
1. Patient violated any requirement of the protocol in Study 014 that would put him/her at risk for continuing treatment with evenamide in Study 015.
2. In the Investigator’s opinion, the patient had a significant worsening of risk for suicidality during Study 014.
3. Patient is experiencing any moderate/severe neurological side effects, other than pre-existing EPS related to antipsychotic treatment prior to enrolling in Study 014.
4. Patient has shown significant worsening of his/her symptoms of schizophrenia between baseline and the final assessment during the 6-week treatment period in Study 014, such that continuing treatment in Study 015 is considered undesirable.
5. Patient demonstrated substantial non-compliance with dosing of the study medication in Study 014.

La presenza di uno qualsiasi dei seguenti criteri porterà all’esclusione di un soggetto dello studio:
1. Il soggetto ha violato uno qualsiasi dei requisiti del protocollo dello studio 014 che lo porrebbe a rischio per il proseguimento del trattamento con evenamide nello studio 015.
2. Secondo lo sperimentatore, il soggetto ha avuto un significativo peggioramento del rischio di suicidio nel corso dello studio 014.
3. Il soggetto manifesta effetti collaterali neurologici moderati o gravi, diversi da sintomi extrapiramidali preesistenti e correlati alla terapia con farmaci antipsicotici assunti prima dell’ingresso nello Studio 014.
4. Il soggetto ha mostrato un peggioramento significativo dei sintomi della schizofrenia tra l’inizio dello studio e la valutazione finale durante il periodo di trattamento di 6 settimane dello Studio 014, in modo tale da ritenere che la prosecuzione del trattamento nello Studio 015 sia sconsigliata.
5. Il soggetto ha mostrato una sostanziale mancanza di aderenza nel trattamento con il farmaco di studio nel corso dello Studio 014.

E.5 End points

E.5.1

Primary end point(s)

Safety will be assessed by the following:
• Adverse events (AEs)
• Vital signs (systolic/diastolic blood pressure, pulse, body temperature, respiratory rate, body weight, BMI, waist circumference)
• Laboratory evaluations (hematology, blood chemistry, and urinalysis; serum prolactin).
• Electrocardiogram (ECG) – 12-lead standard
• Physical examination
• Neurological examination
• Standard eye examination – visual acuity (Snellen chart), visual field, eye muscles, pupillary response, fundus (dilated, if feasible), tonometry, and front part of eyes (eyelids, cornea, conjunctiva, sclera and iris)
• Extrapyramidal Symptom Rating Scale - Abbreviated version (ESRS-A)
• Calgary Depression Scale for Schizophrenia (CDSS).

Valutazioni di sicurezza - Obiettivo di sicurezza primario
La sicurezza verrà valutata in base a quanto segue:
• Eventi avversi (AEs)
• Segni vitali (pressione arteriosa sistolica / diastolica, pulsazioni, temperatura corporea, frequenza respiratoria, peso corporeo, indice di massa corporea, circonferenza addominale)
• Valutazioni di laboratorio (ematologia, ematochimica e analisi delle urine; prolattina sierica).
• Elettrocardiogramma (ECG) - standard a 12 derivazioni
• Esame obiettivo
• Esame neurologico
• Esame oculistico standard: acuità visiva (tabella di Snellen), campo visivo, muscoli oculari, risposta pupillare, fondo (con pupille dilatate, se possibile), tonometria e parte anteriore degli occhi (palpebre, cornea, congiuntiva, sclera e iride)
• Extrapyramidal Symptom Rating Scale - Versione abbreviata (ESRS-A)
• Scala CDSS (Calgary Depression Scale for Schizophrenia).

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety and efficacy evaluations will be performed at Weeks 6, 12, 18, 24 and 36 during scheduled visits at the clinic, and at weeks 30 and 41 during telephone contacts.

Le valutazioni finali di sicurezza e efficaci verranno effettuate alle visite alla settimana 6, 12, 18, 24, 36 e 46 in occasione del ritorno dei pazienti al centro e alla settimana 30 e 41 in occasione di contatti telefonici da parte dello staff del centro.

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

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

Yes

E.8.1.7.1

Other trial design description

in aperto con valutatore in cieco

open-label with blind evaluator

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

India

Malaysia

Sri Lanka

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

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

143

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

150

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)

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

2020-12-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-28

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