Clinical Trials Register

Summary
EudraCT Number:	2013-002447-29
Sponsor's Protocol Code Number:	CL01-ORY-1001
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-09-20
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

2013-002447-29

A.3

Full title of the trial

A phase I study of Human Pharmacokinetics and Safety of ORY-1001, and LSD1 inhibitor, in relapsed or refractory acute leukaemia (AL)

Estudio en fase I de seguridad y farmacocinética humanas de ORY-1001, un inhibidor de LSD1, en leucemia aguda (LA) recurrente o refractaria

A.3.1

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

A study to establish the pharmacokinetics (how the human body processes the drug) and safety of a new anti-cancer drug, ORY-1001 in cancer of blood and bone marrow after treatment or remission

A.4.1

Sponsor's protocol code number

CL01-ORY-1001

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	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	Oryzon Genomics S.A.
B.5.2	Functional name of contact point	Tamara Maes
B.5.3	Address:
B.5.3.1	Street Address	C/Sant Ferran,74
B.5.3.2	Town/ city	Cornellà de Llobregat
B.5.3.3	Post code	08940
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34935151313
B.5.5	Fax number	+34933774028
B.5.6	E-mail	tmaes@oryzon.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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/064/13
D.3 Description of the IMP
D.3.1	Product name	ORY-1001
D.3.2	Product code	ORY-1001
D.3.4	Pharmaceutical form	Concentrate for oral solution
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	ORY-1001
D.3.9.2	Current sponsor code	ORY-1001
D.3.9.3	Other descriptive name	OG-RR
D.3.9.4	EV Substance Code	SUB124833
D.3.10	Strength
D.3.10.1	Concentration unit	µg/m2 microgram(s)/square meter
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 141
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

Refractory or Relapsed acute leukaemia (AL)

Leucemia aguda (LA) recurrente o refractaria

E.1.1.1

Medical condition in easily understood language

Cancer of blood and bone marrow after treatment or remission

Cáncer de la sangre y la médula ósea después del tratamiento o remisión

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10000835
E.1.2	Term	Acute leukemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10024330
E.1.2	Term	Leukemia acute
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10024329
E.1.2	Term	Leukemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10000830
E.1.2	Term	Acute leukaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the safety (hematological and non-hematological toxicities) and tolerability of ORY-1001

Evaluar la seguridad y tolerabilidad de ORY-1001 en humanos

E.2.2

Secondary objectives of the trial

- Characterize the PK of orally administered ORY-1001 in patients with relapsed / refractory AL
- Assess responses (CR/CRi/PR) with ORY-1001 in patients with relapsed or refractory AL, particularly in those with rMLL gene
- Evaluate surrogate PD markers for target engagement

- Describir la farmacocinética (FC) de ORY-1001 en humanos
- Valorar las respuestas (RC/RCi/RP) con ORY-1001 en pacientes con leucemia aguda (LA) recurrente o refractaria, especialmente en aquellos que presentan el gen rMLL
- Evaluar los marcadores de farmacodinámica (PD) indirectos para la unión de fármaco a su diana

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients aged 16 and above.
2. Patients must have relapsed or refractory AL (exluding promyelocytic leukaemia) considered by the investigator ineligible for intensive chemotherapy regimen at that time
3. Patients must have ECOG Performance Status (PS) of 0-2
4. Women of child-bearing potential must have negative serum or urine pregnancy test within two weeks prior treatment start
5. Fertile male or female patients must use highly efficient contraception for the duration of the study and 6 months after the last ORY-1001 dose.
6. Male patients must use condoms to avoid drug exposure of their partner.
7. Patients must be capable of understanding and complying with protocol requirements, and they must be able and willing to sign a written informed consent
8. Life expectancy of at least 2 months

1. Pacientes con edad a partir de 16 años
2. Leucemia aguda (LA) recurrente o refractaria (sin incluir la leucemia promielocítica) que el investigador considere no apta para el régimen quimioterápico intensivo en ese momento
3. Escala de estado funcional (EF) ECOG de 0-2
4. Las mujeres en edad fértil deben presentar una prueba de embarazo en suero u orina negativa dentro de las dos semanas antes del inicio del tratamiento
5. Los pacientes hombres o mujeres fértiles deben usar un método anticonceptivo altamente eficaz durante el período de estudio y 6 meses después de la última dosis de ORY-1001.
6. Los pacientes hombres deben utilizar preservativo con el fin de evitar exponer a su pareja al fármaco.
7. Los pacientes deben poder entender y cumplir con los requisitos que establece el protocolo, y deberán ser capaces de y estar dispuestos a firmar un consentimiento informado por escrito
8. La esperanza de vida es de al menos 2 meses

E.4

Principal exclusion criteria

1. Cancer history that according to the investigator might confound the assessment of the study endpoints
2. Patients with uncontrolled hypertension or diabetes, hepatitis or HIV.
3. Inter-current illness or social situation that will limit compliance with study requirements
4. Pregnancy or lactating / breast feeding
5. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities if entered into the clinical study
6. Acute myeloid leukaemia treatment within the previous 14 days. Hydroxyurea or 6-mercaptopurine are allowed until 12 hours prior study treatment start and after the first treatment block (day 1-5) in case of hyperleucocytosis.
7. Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: Tranylcypromine or Phenelzine.
8. Radiotherapy less than 2 weeks prior to the start of the study

1. Antecedentes de cáncer que, según la opinión del investigador, puedan crear confusión en la evaluación de los criterios de valoración del estudio
2. Pacientes con hipertensión o diabetes insuficientemente controladas, hepatitis o VIH.
3. Patología intercurrente o situación social que pueda afectar al cumplimiento de los requisitos del estudio
4. Pacientes embarazadas o en período de lactancia
5. Cualquier afección médica que, en opinión del investigador, ponga al paciente en una situación inaceptable de alto riesgo de toxicidad al participar en el estudio clínico
6. Tratamiento de leucemia mieloide aguda recibido en los 14 días anteriores. La hidroxiurea o la 6-mercaptopurina están permitidas hasta 12 horas antes del inicio del tratamiento del estudio y tras la primera parte del tratamiento (días 1-5) en caso de hiperleucocitosis.
7. Los pacientes tratados con antidepresivos informaron una actividad inhibitoria KDM1A/LSD1: Tranilcipromina o fenelzina.
8. Radioterapia aplicada menos de 2 semanas antes del inicio del estudio

E.5 End points

E.5.1

Primary end point(s)

The PK of ORY-1001 in patients with relapsed /refractory AL
The PD of ORY-1001 in patients with relapsed / refractory AL
Assess maximum tolerated dose of ORY-1001 in humans as a monotherapy
Adverse events assessed by patient reporting
Clinical observations and vital signs
ECG
Laboratory data

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients are to attend study centre visits during baseline (within 14 days before the first dose) and at defined days after start of treatment. Assessments will be made at baseline, day 1, 2, 3, 4, 5, 6, 7 of the first treatment block and on the first, third and fifth day of administration for the 3 other treatment blocks in the 28 day cycle. Additional visits may be made for safety reasons. Hematology samples (5ml) will be obtained on the first, third and fifth day of each treatment block. Samples for the analysis of blood chemistry (5ml) will be obtained weekly on the first day of each treatment block. A follow up visit will be performed at a minimum of 30 days after the last ORY-1001 dose.

E.5.2

Secondary end point(s)

Remission rate (CR + CRi)
Gene expression changes in blood cells

E.5.2.1

Timepoint(s) of evaluation of this end point

DAY1: 0h (pre-dosing)2h, 4h, 6h, 8h, 12h, 18h
DAY2: 24h, 28h,
DAY3: 48h, 52h,
DAY4: 72h, 76h,
DAY5: 96h,100h,
During the next 3 treatment blocks in the first cycle, samples will be taken only on the first day and the fifth day, just prior to administration

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

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

dose escalation followed by an extension cohort at the MTD

escalado de dosis seguida de un cohorte de extensión a la DMT

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

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.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

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)

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

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)

Additional cycles of therapy may be decided upon on a case by case basis in mutual agreement between the investigator and Oryzon genomics

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

2013-12-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-31

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

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