Clinical Trials Register

Summary
EudraCT Number:	2017-002838-23
Sponsor's Protocol Code Number:	CL02-ORY-2001MS
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-07-21
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

Spain - AEMPS

A.2

EudraCT number

2017-002838-23

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled, 3-arm, 36 weeks parallel-group study to evaluate the safety and tolerability of ORY-2001 in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)

Estudio aleatorizado, doble ciego, controlado con placebo, de grupos paralelos, con 3 grupos y de 36 semanas de duración, para evaluar la seguridad y la tolerabilidad de ORY-2001 en pacientes con esclerosis múltiple remitente-recurrente (EMRR) y esclerosis múltiple secundaria progresiva (EMSP).

A.3.1

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

A.4.1

Sponsor's protocol code number

CL02-ORY-2001MS

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	Oryzon Genomics S. A
B.1.3.4	Country	Spain
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	Oryzon Genomics S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Trial Form Support
B.5.2	Functional name of contact point	Laia Torruella
B.5.3	Address:
B.5.3.1	Street Address	Consell de cent 334
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08009
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034931850200
B.5.6	E-mail	laia.torruella@tfscro.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	ORY2001
D.3.2	Product code	ORY2001
D.3.4	Pharmaceutical form	Capsule
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	Not yet requested
D.3.9.2	Current sponsor code	ORY2001
D.3.9.3	Other descriptive name	PHENYLCYCLOPROPYLAMINE DERIVATIVES AND DUAL LSD1/MAO-B (LYSINE-SPECIFIC DEMETHYLASE 1 AND MONOAMINE OXIDASE-B) INHIBITOR
D.3.9.4	EV Substance Code	SUB179357
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.6 to 1.2
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	Capsule
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

patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)

pacientes con esclerosis múltiple remitente-recurrente (EMRR) y esclerosis múltiple secundaria progresiva (EMSP).

E.1.1.1

Medical condition in easily understood language

patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)

pacientes con esclerosis múltiple remitente-recurrente (EMRR) y esclerosis múltiple secundaria progresiva (EMSP).

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	10063400
E.1.2	Term	Secondary progressive multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

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	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system 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 two doses of ORY-2001 compared to placebo in multiple sclerosis (MS) subjects.

Evaluar la seguridad y tolerabilidad de dos dosis de ORY-2001 en comparación con placebo en pacientes con esclerosis múltiple (EM)

E.2.2

Secondary objectives of the trial

To assess the effect of two doses of ORY-2001 on inflammatory Magnetic Resonance Imaging (MRI) measures compared to placebo in MS subjects.

Evaluar el efecto de dos dosis de ORY-2001 sobre el nivel de inflamación determinado mediante resonancia magnética (RM) en comparación con placebo en pacientes con EM.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients aged 18-65 years, inclusive
2. Diagnosis of MS (McDonald Criteria 2010)
3. Relapsing-Remitting or Secondary Progressive MS phenotypes
4. Active MS within the previous 12 months, defined as:
a. At least one relapse, or
b. At least one T1 Gadolinium (Gd)-enhancing lesion*, or
c. At least one new or enlarging T2 lesion*
* Subjects without evidence of active MS in the last 12 months can be included if at least one of these two criteria are fulfilled at the screening MRI performed up to 7 days prior to randomization
5. Expanded Disability Status Scale (EDSS) at screening and baseline visit between 0 and 6.5
6. Fertile male and female must use highly efficient contraception from Screening visit until the last treatment day (including open-label period), defined as:
i. A method with less than 1% failure rate (e.g. permanent sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner)
OR
ii. The use of two methods of contraception (e.g. one barrier method [condom, diaphragm or cervical/vault caps] with spermicide and one hormonal contraceptive [e.g. combined oral contraceptives, patch, vaginal ring, injectables and implants])
7. Patient must sign and date a written informed consent prior to entering the study

1. Pacientes de entre 18 y 65 años, inclusive.
2. Diagnóstico de EM (según los criterios de McDonald de 2010).
3. Fenotipo de EM remitente-recurrente o secundaria progresiva.
4. EM activa en los últimos 12 meses, definida como:
a. Como mínimo una recidiva, o
b. Como mínimo una lesión con captación de gadolinio (Gd) en T1,* o
c. Como mínimo una lesión nueva o con aumento de tamaño en T2.*
* Puede incluirse a pacientes sin indicios de EM activa en los últimos 12 meses si cumplen por lo menos uno de estos dos criterios en la RM de la selección, realizada hasta 7 días antes de la aleatorización.
5. Puntuación en la Escala ampliada del estado de discapacidad (EDSS) en la selección y la visita inicial entre 0 y 6,5.
6. Los hombres y las mujeres fértiles deberán usar métodos anticonceptivos con una eficacia elevada desde la visita de selección hasta el último día del tratamiento (incluido el período abierto), definidos como:
i. Un método con menos de un 1 % de tasa de ineficacia (p. ej., esterilización permanente, implantes hormonales, inyecciones hormonales, algunos dispositivos intrauterinos o pareja sometida a vasectomía).
O BIEN
ii. El uso de dos métodos anticonceptivos (p. ej., un método de barrera [preservativo, diafragma o capuchón cervical] con espermicida y un anticonceptivo hormonal [p. ej., anticonceptivos orales combinados, parche, anillo vaginal, inyectables o implantes]).
7. Los pacientes deben firmar y fechar un consentimiento informado por escrito antes de la inclusión en el estudio

E.4

Principal exclusion criteria

1. Previous history of central nervous system (CNS) or psychiatric clinical disease that according to the investigator might confound the assessment of the study endpoints
2. CNS or psychiatric current therapies specifically anti-depressants as tranylcypromine or phenelzine and Monoamine Oxidase (MAO) therapies
3. Cancer history or cancer therapies that according to the investigator might confound the assessment of the study endpoints
4. Patients with uncontrolled hypertension (uncontrolled in the opinion of the investigator), and diabetes (consistent glucose level >100 mg/dL) or hepatitis (persistent liver inflammation)
5. Inter-current illness or social situation that will limit compliance with study requirements
6. MS relapse in the 6 weeks prior to randomization
7. Treatment with any investigational medicinal product within twelve weeks prior to randomization or 5 half-lives, whichever is longer
8. Treatment with interferon beta or glatiramer acetate in the four weeks prior to randomization
9. Treatment with fingolimod or dimethyl fumarate in the twelve weeks prior to randomization
10. Treatment with azathioprine or methotrexate in the 6 months prior to randomization
11. Treatment with teriflunomide in the previous year unless a successful wash-out procedure has been performed (plasmatic levels below 0.02 mg/l) prior to randomization
12. Treatment with natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine, mitoxantrone or cyclophosphamide in the year prior to randomization
13. Concomitant treatment with known MAO inhibitors (as rasagiline) or with other drugs with known incompatibility with MAO inhibitors or contraindications to receive MAO inhibitors
14. A known history of hypersensitivity to Gd
15. Participation in another clinical trial with an investigational drug product not completed within the 30 days prior to enrolment
16. Abnormal or clinically relevant haematology and biochemistry laboratory tests values (including kidney function profile)
17. Abnormal clinical evaluation
18. Abnormal or clinically relevant electrocardiogram (ECG) findings
19. Positive tuberculosis, human immunodeficiency virus (HIV), hepatitis C or hepatitis B (Hepatitis B surface antigen [HbsAg]) serology (test performed at screening)
20. Pregnancy or breast feeding
21. History of alcohol or substance abuse

1. Antecedentes de enfermedad del sistema nervioso central (SNC) o de enfermedad psiquiátrica clínica que, según el criterio del investigador, puedan constituir un factor de confusión en la evaluación de los criterios de valoración del estudio.
2. Tratamiento psiquiátrico o del SNC actual, específicamente antidepresivos como la tranilcipromina o la fenelzina, y tratamientos dirigidos a la monoaminooxidasa (MAO).
3. Antecedentes de cáncer o tratamientos antineoplásicos que, según el criterio del investigador, puedan constituir un factor de confusión en la evaluación de los criterios de valoración del estudio.
4. Hipertensión no controlada (según el criterio del investigador) y diabetes (nivel de glucosa >100 mg/dl de forma constante) o hepatitis (inflamación hepática persistente).
5. Enfermedad intercurrente o situación social que limite el cumplimiento de los requisitos del estudio.
6. Recidiva de la EM en las 6 semanas previas a la aleatorización.
7. Tratamiento con cualquier medicamento en investigación en las 12 semanas, o 5 semividas, previas a la aleatorización, lo que sea más largo.
8. Tratamiento con interferón beta o acetato de glatirámero en las 4 semanas previas a la aleatorización.
9. Tratamiento con fingolimod o dimetilfumarato en las 12 semanas previas a la aleatorización.
10. Tratamiento con azatioprina o metotrexato en los 6 meses previos a la aleatorización.
11. Tratamiento con teriflunomida en el año anterior, a menos que se haya realizado un procedimiento de lavado farmacológico adecuado antes de la aleatorización (niveles plasmáticos inferiores a 0,02 mg/l).
12. Tratamiento con natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribina, mitoxantrona o ciclofosfamida en el año previo a la aleatorización.
13. Tratamiento concomitante con inhibidores conocidos de la MAO (como la rasagilina) o con otros fármacos con incompatibilidad conocida con los inhibidores de la MAO, o pacientes en los que los inhibidores de la MAO estén contraindicados.
14. Antecedentes conocidos de hipersensibilidad al Gd.
15. Participación en otro ensayo clínico con un medicamento en investigación que no haya concluido en los 30 días previos a la inclusión.
16. Valores anómalos o clínicamente relevantes en los valores analíticos de hematología y bioquímica (incluido el perfil de la función renal).
17. Evaluación clínica anómala.
18. Hallazgos anómalos o clínicamente relevantes en el electrocardiograma (ECG).
19. Serología positiva para la tuberculosis, el virus de la inmunodeficiencia humana (VIH) o la hepatitis C o B (antígeno de superficie de la hepatitis B: HbsAg). Prueba realizada durante la selección.
20. Embarazo o lactancia.
21. Antecedentes de abuso de alcohol o drogas.

E.5 End points

E.5.1

Primary end point(s)

• Number, frequency and severity of Adverse Events (AEs).
• Number, frequency and severity of Serious Adverse Events (SAEs)
• Number and percentage of withdrawn patients due to AEs
• Change from baseline in physical examination, vital signs and ECG parameters
• Frequency of physical examination parameters, vital signs and ECG parameters of potential clinical concern
• Change from baseline in clinical laboratory parameters (hematology, clinical chemistry and urinalysis)
• Frequency of clinical laboratory parameters (hematology, clinical chemistry and urinalysis) of potential clinical concern
• Use of concomitant medication

• Número, frecuencia e intensidad de los acontecimientos adversos (AA).
• Número, frecuencia e intensidad de los acontecimientos adversos graves (AAG).
• Número y porcentaje de pacientes que se retiran a causa de los AA.
• Cambios en la exploración física, las constantes vitales y los parámetros del ECG respecto al estado inicial.
• Frecuencia con que se observan parámetros de la exploración física, constantes vitales o parámetros del ECG que puedan suponer un problema desde el punto de vista clínico.
• Cambios en los parámetros analíticos (hematología, bioquímica clínica y análisis de orina) respecto a los valores iniciales.
• Frecuencia con que se observan parámetros analíticos (hematología, bioquímica clínica y análisis de orina) que puedan suponer un problema desde el punto de vista clínico.
• Uso de medicación concomitante.

E.5.1.1

Timepoint(s) of evaluation of this end point

End points will be evaluated at the end of study vs the baseline values.

Los end points del estudio serán evaluados al final del mismo comparándolos con los valores de la visita basal

E.5.2

Secondary end point(s)

• Cumulative number of Combined Unique Active lesions (CUAL) (defined as Gd-enhancing T1-weighted lesions and non-enhancing new/enlarging T2-weighted lesions) at weeks 8, 12, 24, 32 and 36 as assessed through MRI.

• Número acumulado de lesiones activas combinadas únicas (CUAL, por sus siglas en inglés; definidas como lesiones que captan Gd en la imagen ponderada en T1, o lesiones nuevas o con aumento de tamaño que no captan Gd en la imagen ponderada en T2) en las semanas 8, 12, 24, 32 y 36, evaluadas mediante RM

E.5.2.1

Timepoint(s) of evaluation of this end point

at weeks 8, 12, 24, 32 and 36

A la semana 8, 12, 24, 32 y 36

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tolerabilidad

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

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

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

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

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

The end of study is defined as the date of the last subject’s last visit (EoS visit for the last subject included).

El final del estudio se define como la fecha de la última visita del último paciente (última visita del estudio para el último paciente incluido)

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 months

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:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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)

For the open label extension phase under treatment, patients who were originally randomised to ORY-2001 will continue their assigned treatment and those receiving the placebo will be re-allocated to ORY-2001, 0.6 mg fiw or 1.2 mg fiw, according to the predefined randomisation schedule

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

2017-10-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-25

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

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