Clinical Trials Register

Summary
EudraCT Number:	2015-002874-19
Sponsor's Protocol Code Number:	63935937MDS3001
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:	2021-09-30
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

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

Uno studio per valutare imetelstat (JNJ-63935937) in soggetti dipendenti dalle trasfusioni con sindrome mielodisplastica (MDS) con rischio IPSS basso o intermedio-1 recidivante o refrattaria al trattamento con gli agenti stimolanti l’eritropoiesi (ESA)

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).

Uno studio per valutare imetelstat (JNJ-63935937) in soggetti con sindrome mielodisplastica (MDS) con rischio IPSS basso o intermedio-1

A.3.2

Name or abbreviated title of the trial where available

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 CILAG SPA
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	JANSSEN CILAG INTERNATIONAL NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	00310715242166
B.5.5	Fax number	00310715242110
B.5.6	E-mail	ClinicalTrialsEU@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.3.4	Pharmaceutical form	Powder for solution for injection
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.3.9.4	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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

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)

Sindrome mielodisplastica

E.1.1.1

Medical condition in easily understood language

Myelodysplastic syndrome (MDS)

Sindrome mielodisplastica

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	20.0
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: valutare l’efficacia e la sicurezza di imetelstat nei soggetti dipendenti dalle trasfusioni con MDS di rischio basso o intermedio-1 recidivante o refrattaria al trattamento con gli ESA.
Parte 2: confrontare l’efficacia, in termini di indipendenza dalle trasfusioni (TI) di eritrociti (RBC), di imetelstat rispetto al placebo in soggetti dipendenti dalle trasfusioni con MDS di rischio basso o intermedio-1 recidivante o refrattaria al trattamento con gli ESA.

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

•Valutare la sicurezza di imetelstat in soggetti con MDS
•Valutare il tempo di indipendenza dalle trasfusioni di RBC (RBC TI) e la durata di RBC TI
•Valutare la percentuale di miglioramento ematologico
•Valutare le percentuali di remissione completa (CR) o remissione parziale (PR)
•Valutare la sopravvivenza globale (OS)
•Valutare il tempo alla progressione in leucemia mieloide acuta (AML)
•Valutare la percentuale e la quantità di prestazioni sanitarie di supporto, tra cui trasfusioni e fattori di crescita mieloidi
•Valutare la farmacocinetica e l’immunogenicità di imetelstat in soggetti con MDS
•Valutare l’effetto del trattamento con imetelstat sui risultati riportati dal paziente (PROs)
•Valutare l’effetto del trattamento sull’utilizzo delle risorse mediche

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Criterion modified per Amendment ITA-1.
1.1. Man or woman =18 and =75 years of age;
2. Criterion modified per Amendment 1.
2.1. Diagnosis of MDS according to WHO criteria 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 (Attachment 1);
3 IPSS low Risk or intermediate-1 risk MDS (Attachment 3);
4 Criterion modified per Amendment 1/ITA-1:
4.1 RBC transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry (defined in Section 3.1); pre-transfusion Hb should be =9.0 g/dL to count towards the 4 units total;
5 Has MDS that is relapsed/refractory to ESA treatment; as defined by meeting any one of the criteria below:
5.1 Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa 40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent agent/dose), without having achieved a Hb rise =1.5 g/dL or decreased RBC transfusion requirement by at least 4 units over 8 weeks
5.2 Transfusion dependence or reduction in Hb by =1.5 g/dL after hematologic improvement, in the absence of another explanation
5.3 Criterion 5.3 replaced by criterion 5.4 per Amendment 1/ITA-1.
5.4 Endogenous serum EPO level >500 mU/mL;
13 Subjects with the del(5q) karyotype are eligible if they have failed treatment with lenalidomide. Failure is defined as either: 1) having received at least 3 months of lenalidomide treatment without RBC transfusion benefit (IWG 2006); 2) progression or relapse after Hematologic Improvement with lenalidomide (IWG 2006); 3) discontinuation of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a contraindication.

1. Criterio modificato per Emendamento ITA-1.
1.1. Sesso maschile o femminile con età =18 anni e =75 anni.
2. Criterio modificato in accordo all’Emendamento 1/ITA-1;
2.1. Diagnosi di MDS secondo i criteri WHO confermata da agoaspirato e biopsia del midollo osseo eseguiti entro le 12 settimane precedenti all’ingresso nello studio. Lo sponsor deve esaminare e approvare il referto dell’agoaspirato e della biopsia diagnostici del midollo osseo rilasciato da un laboratorio locale (Allegato 1).
3. MDS con rischio IPSS basso o intermedio-1 (Allegato 3).
4.Criterio modificato in accordo all’Emendamento 1/ITA-1;
4.1 Dipendenza dalle trasfusioni di RBC, definita come necessità di almeno 4 unità di RBC trasfuse nell’arco di un periodo di 8 settimane durante le 16 settimane precedenti all’ingresso nello studio (definito nella Sezione 3.1); il livello di emoglobina precedente alla trasfusione deve essere =9,0 g/dL affinché la trasfusione contribuisca al totale di 4 unità.
5. MDS recidivante o refrattaria al trattamento con gli ESA, in linea con uno dei seguenti criteri:
5.1. assunzione di almeno 8 settimane di trattamento con una dose settimanale minima di epoetina alfa 40.000 U, epoetina beta 30.000 U o darbepoetina alfa 150 mcg (o dose/agente equivalente), senza aver ottenuto un aumento dell’emoglobina =1,5 g/dL o aver ridotto la necessità di trasfusioni di RBC di almeno 4 unità nell’arco di 8 settimane;
5.2.dipendenza dalle trasfusioni o riduzione del livello di emoglobina di =1,5 g/dL dopo il miglioramento ematologico, in assenza di un’altra spiegazione;
5.3.Criterio 5.3 sostituito dal criterio 5.4 in accordo all’Emendamento 1/ITA-1
5.4. livello sierico di EPO endogena >500 mU/mL.
13. I soggetti con cariotipo del(5q) sono eleggibili se hanno fallito il trattamento con lenalidomide. Il fallimento è definito come: 1) aver ricevuto almeno 3 mesi di trattamento con lenalidomide senza beneficio nelle trasfusione di RBC (IWG 2006); 2) progressione o recidiva dopo miglioramento ematologico con lenalidomide (IWG 2006); 3) sospensione di lenalidomide a causa di tossicità; o 4) soggetto non in grado di ricevere lenalidomide a causa di controindicazione.

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

-Soggetti con allergie, ipersensibilità o intolleranza note a imetelstat o ai suoi eccipienti
-Soggetti che hanno assunto un farmaco sperimentale o utilizzato un dispositivo medicale sperimentale invasivo entro i 30 giorni precedenti all’ingresso nello studio oppure attuale arruolamento in uno studio sperimentale.
-Precedente trattamento con imetelstat.
-Assunzione di chemioterapia, terapia immunomodulatoria o immunosoppressiva, corticosteroidi >30 mg/giorno di prednisone o equivalente o trattamento con fattori della crescita entro i 28 giorni precedenti all’ingresso nello studio.
-Assunzione di altri trattamenti per la MDS entro le 4 settimane precedenti all’ingresso nello studio

E.5 End points

E.5.1

Primary end point(s)

Percentuale dei partecipanti senza trasfuzione di globuli rossi (RBC) durante il periodo di 8 settimane consecutive

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

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

8 settimane

E.5.2

Secondary end point(s)

1 -Safety profiles of imetelstat in subjects with MDS (eg, incidence intensity, and type of adverse events, vital signs measurements, clinical laboratory values, ECGs, and deaths); 2 -24-week RBC TI rate, defined as the proportion of subjects without any RBC transfusion during any consecutive 24 weeks (168 days) starting from Study Day 1; 3 -Time to the 8-week RBC TI, defined as the interval from Study Day 1 to the first day of the first 8-week RBC TI period; 4.- Duration of RBC TI, defined as the first day of the first 8-week RBC TI period to the date of the first RBC transfusion after the TI period; 5. Rate of hematologic improvement, including HI-E, per IWG 2006;

1-profili di sicurezza di imetelstat in soggetti con MDS (per esempio, incidenza, intensità, tipo di Eventi Avversi, Misurazione dei segni vitali, valori clinici di laboratorio, ECG e decessi) 2-la percentuale di indipendenza dalle trasfusioni di RBC (RBC TI) nelle 24 settimane, definita come la proporzione di soggetti senza trasfusioni da RBC durante un periodo di 24 settimane consecutive (168gg) che iniziano dal giorno 1 dello studio. 3-tempo trascorso al raggiungimento delle 8 settimane di RBC-TI, definito come l'intervallo di tempo dal giorno 1 dello studio al primo giorno del primo periodo di 8 settimane di RBC TI 4.durata di RBC TI definita come il primo giorno del primo periodo di 8 settimane di RBC TI fino alla data della prima trasfusione di RBC dopo il periodo TI 5.frequenza di miglioramento ematologico, incluso HI-E in accordo a IWG 2006

E.5.2.1

Timepoint(s) of evaluation of this end point

1/ up to follow-up (30 days posttreatment [approximately 2 years]); 2-5/ up to 2 years after enrollment of the last participant

1/Fino al Follow-up (30gg dopo il trattamento [approssimativamente 2 anni]) 2-5/Fino a 2 anni dopo l'arruolamento dell'ultimo soggetto

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

Immunogenicità e biomarcatori

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

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

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

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

Brazil

Korea, Republic of

Mexico

Russian Federation

United States

Belgium

France

Germany

Italy

Netherlands

Spain

Switzerland

United Kingdom

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.

La fine dello studio avverrà 2 anni dopo l'ingresso nello studio dell'ultimo soggetto o nel momento in cui lo Sponsor deciderà di interrompere lo studio, a seconda dell'evento che si verifica per primo

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.

Lo Sponsor assicurerà che i soggetti che beneficiano del trattamento con imetelstat potranno continuare il trattamento dopo la fine dello studio

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

2019-07-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-08

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

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