Clinical Trials Register

Summary
EudraCT Number:	2015-002874-19
Sponsor's Protocol Code Number:	63935937MDS3001
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:	2015-10-05
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

Spain - AEMPS

A.2

EudraCT number

2015-002874-19

A.3

Full title of the trial

A Study to Evaluate Imetelstat (JNJ-63935937) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

Estudio para evaluar Imetelstat (JNJ-63935937) en sujetos con Síndrome Mielodisplásico (SMD) con un IPSS de riesgo bajo o intermedio-1 dependientes de transfusiones en recaída o refractarios al tratamiento con Agentes Estimulantes de la Eritropoyesis (AEE).

A.3.1

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

Study to Evaluate Imetelstat (JNJ-63935937) in Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS).

Estudio para evaluar Imetelstat (JNJ-63935937) en sujetos con Síndrome Mielodisplásico (SMD) con un IPSS de riesgo bajo o intermedio-1.

A.4.1

Sponsor's protocol code number

63935937MDS3001

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	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
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	Janssen Research & Development, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag S.A.
B.5.2	Functional name of contact point	Global Clinical Operations Spain
B.5.3	Address:
B.5.3.1	Street Address	Paseo de las Doce Estrellas 5-7
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28042
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34917228100
B.5.5	Fax number	+34917228628
B.5.6	E-mail	agonza45@its.jnj.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	Imetelstat sodium
D.3.2	Product code	JNJ-63935937
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Imetelstat sodium
D.3.9.1	CAS number	1007380-31-5
D.3.9.2	Current sponsor code	JNJ-63935937
D.3.9.3	Other descriptive name	IMETELSTAT SODIUM
D.3.9.4	EV Substance Code	SUB174121
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	210
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

Myelodysplastic syndrome (MDS)

Síndrome mielodisplásico

E.1.1.1

Medical condition in easily understood language

Myelodysplastic syndrome (MDS)

Síndrome mielodisplásico

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	HLT
E.1.2	Classification code	10028536
E.1.2	Term	Myelodysplastic syndromes
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1: To evaluate the efficacy and safety of imetelstat in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

Part 2: To compare the efficacy, in terms of RBC TI, of imetelstat to placebo in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

Parte 1: Evaluar la eficacia y seguridad de imetelstat en sujetos con SMD de riesgo bajo o intermedio-1 dependientes de transfusiones que hayan recaído o sean refractarios al tratamiento con AEE.
Parte 2: Comparar la eficacia en términos de independencia de transfusiones (IT) de células sanguíneas rojas de imetelstat con placebo en sujetos con SMD de riesgo bajo o intermedio-1 dependientes de transfusiones que hayan recaído o sean refractarios al tratamiento con AEE.

E.2.2

Secondary objectives of the trial

- To assess the safety of imetelstat in subjects with MDS
- To assess the time to RBC TI and duration of RBC TI
- To assess the rate of hematologic improvement
- To assess the rates of CR or PR
- To assess OS
- To assess time to progression to AML
- To assess the rate and amount of supportive care, including transfusions and myeloid growth factors
- To evaluate the pharmacokinetics and immunogenicity of imetelstat in subjects with MDS
- To assess the effect of imetelstat treatment on patient reported outcomes (PROs)
- To assess the effect of treatment on medical resource utilization

- Evaluar la seguridad de imetelstat en pacientes con SMD
- Evaluar el tiempo hasta la IT de eritrocitos y su duración
- Evaluar la tasa de mejoría hematológica
- Evaluar las tasas de remisión completa (RC) o remisión parcial (RP)
- Evaluar la supervivencia global (SG)
- Evaluar el tiempo hasta la progresión a leucemia mieloide aguda (LMA)
- Evaluar la tasa y la cantidad de tratamiento de soporte, incluidos las transfusiones y los factores de crecimiento mieloides
- Evaluar la farmacocinética e inmunogenicidad de imetelstat en pacientes con SMD
- Evaluar el efecto del tratamiento con imetelstat en los resultados comunicados por los pacientes (RCP)
- Evaluar el efecto del tratamiento sobre la utilización de recursos médicos

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Man or woman greater than or equal to (>=) 18 years of age
- Diagnosis of myelodysplastic syndrome (MDS) according to WHO criteria or French-American-British (FAB) classification confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Study Entry. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be reviewed and approved by the sponsor
- International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
- Red blood cell (RBC) transfusion dependent, defined as requiring 4 units RBC over 8 weeks during the 12 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

1. Varones o mujeres >= 18 años de edad
2. Diagnóstico de SMD según los criterios de la OMS o la clasificación franco-americano-británica (FAB) confirmado por un aspirado y biopsia de médula ósea en el plazo de 12 semanas antes de la entrada en el estudio. El promotor debe revisar y aprobar un informe del laboratorio local de este aspirado y biopsia de médula ósea para el diagnóstico
3. SMD de riesgo bajo o intermedio-1 según el IPSS.
4. Dependencia de trasfusiones de eritrocitos, definida como la necesidad de 4 unidades de eritrocitos durante 8 semanas a lo largo de las 12 semanas anteriores a la entrada en el estudio; los niveles de Hb previos a la trasfusión deben ser <= 9,0 g/dl para computar el total de las 4 unidades;
5. Estado funcional del ECOG 0, 1 o 2

E.4

Principal exclusion criteria

- Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
- Participant has received an investigational drug or used an invasive investigational medicaldevice within 30 days prior to Study Entry or is currently enrolled in an investigational study
- Prior treatment with imetelstat
- Have received any chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 milligram per day prednisone or equivalent, or growth factor treatment within 28 days prior to study entry
- Have received other treatments for MDS within 4 weeks prior to Study Entry

1.Pacientes que presenten alergia, hipersensibilidad o intolerancia conocidas a imetelstat o a sus excipientes
2.Pacientes que hayan recibido un fármaco en investigación o utilizado un dispositivo médico invasivo en investigación en los 30 días anteriores a la entrada en el estudio o que estén participando actualmente en un estudio de investigación;
3.Tratamiento previo con imetelstat;
4. Haber recibido cualquier quimioterapia, tratamiento inmunomodulador o inmunosupresor, corticosteroides a una dosis >30 mg/día de prednisona o equivalente o tratamiento con factores de crecimiento en los 28 días previos a la entrada en el estudio;
5. Haber recibido otros tratamientos para el SMD en el plazo de 4 semanas antes de la entrada en el estudio

E.5 End points

E.5.1

Primary end point(s)

Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 8 week period.

Porcentaje de pacientes sin ninguna transfusión de eritrocitos durante cualesquiera 8 semanas consecutivas.

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

8 semanas

E.5.2

Secondary end point(s)

1/ Number of Participants with Adverse Events (AEs)
2/ Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 24 week period
3/ Time to the 8-week RBC transfusion independence (TI)
4/ Duration of RBC TI
5/ Percentage of Participants with hematologic improvement
6/ Percentage of Participants with Complete remission (CR) or Partial remission (PR) as Per International Working Group (IWG) Response CriteriaI 2006
7/ Overall survival
8/ Time to Progression to Acute Myeloid Leukemia
9/ Percentage of Participants with Transfusion
10/ Amount of Transfusions
11/ Percentage of Participants receiving any myeloid growth factors
12/ Change from baseline in Functional Assessment of Cancer Therapy -Anemia-Related Effects (FACT-An) Score and EuroQol-EQ-5D-5L ESA (EQ-5D-5L) Score
13/ Maximum Observed Plasma Concentration (Cmax)
14/ Area under the drug concentrationplasma time curve from time zero to last measurable concentration (AUC0-t)
15/ Percentage of Participants with antibodies to imetelstat
16/ Medical resource utilization data

1/ Numero de participantes con eventos adversos
2/Porcentaje de pacientes sin ninguna transfusión de eritrocitos durante cualesquiera 24 semanas consecutivas.
3/El tiempo hasta la IT de eritrocitos que dure al menos 8 semanas.
4/ Duración de TI de eritrocitos.
5/Tasa de mejoría hematológica.
6/Tasas de RC o RP según los criterios de respuesta del IWG de 2006.
7/Supervivencia global.
8/El tiempo hasta la progresión a LMA.
9/Tasa de transfusiones.
10/Cantidad de transfusiones.
11/Tasa del uso de factores de crecimiento mieloides.
12/Variación de las puntuaciones de FACT-An y EQ-5D-5L respecto al valor basal.
13/Cmax.
14/AUC0-t.
15/Porcentaje de pacientes con anticuerpos frente a imetelstat.
16/ Datos de utilización de recursos médicos

E.5.2.1

Timepoint(s) of evaluation of this end point

1/ up to follow-up (30 days posttreatment [approximately 2 years])
2-12/ up to 2 years after enrollment of the last participant
13-14/ During treatment (approximately 2 years)
15-16/ up to 2 years after enrollment of the last participant

1/ Hasta fase de seguimiento (30 dias postratamiento (aproximadamente 2 años)).
2-12/ Hasta 2 años después de la inclusión del último paciente.
13-14/Durante el tratamiento (aproximadamente 2 años).
15-16/hasta dos años después de la inclusión del último paciente

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity
Biomarker

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)

Yes

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

Belgium

Brazil

France

Germany

Italy

Korea, Republic of

Mexico

Netherlands

Russian Federation

Spain

Switzerland

United Kingdom

United States

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 the Study is defined as 2 years after Study Entry of the last subject or anytime the sponsor terminates the study, whichever comes first.

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

140

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

140

F.4.2.2

In the whole clinical trial

200

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 sponsor will ensure that subjects benefiting from treatment with imetelstat will be able to continue treatment after the End of the Study.

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

2015-11-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-17

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