Clinical Trials Register

Summary
EudraCT Number:	2013-004328-12
Sponsor's Protocol Code Number:	Europe
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-08
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

Germany - PEI

A.2

EudraCT number

2013-004328-12

A.3

Full title of the trial

Prospective validation of a predictive model of response to romiplostim in patients with IPSS low or intermediate-1 risk myelodysplastic syndrome (MDS) and thrombocytopenia - the EUROPE-trial

A.3.1

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

Assessment of a predictive response model for romiplostim in patients with low or intermediate-1 risk myelodysplastic syndrome (MDS) and thrombocytopenia - the EUROPE-trial

A.3.2

Name or abbreviated title of the trial where available

Europe

A.4.1

Sponsor's protocol code number

Europe

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02335268

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	GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
B.1.3.4	Country	Germany
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	Amgen
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
B.5.2	Functional name of contact point	Sponsor Office
B.5.3	Address:
B.5.3.1	Street Address	Almstadtstrasse 7
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10119
B.5.3.4	Country	Germany
B.5.4	Telephone number	004935125933240
B.5.5	Fax number	004935125933198
B.5.6	E-mail	marwa.aly@gwtonline.de

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	Yes
D.2.1.1.1	Trade name	Nplate
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Nplate
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N-plate
D.3.9.1	CAS number	267639-76-9
D.3.9.2	Current sponsor code	AMG531
D.3.9.3	Other descriptive name	ROMIPLOSTIM
D.3.9.4	EV Substance Code	SUB27756
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1 to 10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Patients with IPSS low or intermediate-1 risk myelodysplastic syndrome (MDS) and thrombocytopenia

E.1.1.1

Medical condition in easily understood language

Patients with low or intermediate-1 risk myelodysplastic syndrome (MDS) and decrease in functional platelet cells

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10068361
E.1.2	Term	MDS
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to investigate prospectively whether the current TPO level based response model can predict response to romiplostim in thrombocytopenic patients with IPPS low/int-1 MDS

E.2.2

Secondary objectives of the trial

Secondary objectives are Safety, bleeding events, AML evolution, peripheral blasts during therapy,
identification of molecular parameters associated with response and progression

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet the following inclusion criteria tobe eligible for the study,

1. Must understand and voluntarily sign an informed consent form
2. Age > 18 years at the time of signing the informed consent form
3. Must be able to adhere to the study visit schedule and other protocol requirements
4. Diagnosis of MDS using the WHO classification for myeloid neoplasms (Vardiman et al, 2002) as assessed during the screening period
5. Per MDS IPSS, low or intermediate-1 risk MDS as assessed during the screening period
6. The mean of the 2 platelet counts taken within 4 weeks prior to stratification must be:
• ≤ 30 x 109/L (with no individual count > 30 x 109/L during the screening period), with or without a history of bleeding associated with the diagnosis of MDS, OR
• < 50 x 109/L (with no individual count >60 x 109/L during the screening period), with a history of bleeding associated with the diagnosis of MDS
(A standard of care platelet count taken prior to Informed consent may be used as 1 of the 2 counts taken within 4 weeks prior to randomization)
7. Adequate liver function, as evidenced by ALT ≤ 3 times the laboratory normal range, AST ≤ 3 times the laboratory normal range and total bilirubin ≤ 2 times the laboratory normal range
8. Bone marrow aspirate (central diagnostics) with cytogenetics (local) within 8 weeks of starting first dose of investigational product
9. Female subjects of childbearing potential† must:
o Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea

E.4

Principal exclusion criteria

1. Pregnant or lactating females
2. IPSS intermediate-2 or high-risk
3. ≥ 5% blasts in the bone marrow as determined by central morphology during screening
4. Previous treatment with any thrombopoietic growth factor
5. Prior history of hematopoietic stem cell transplantation
6. Active or uncontrolled disease including infections or cancer
7. Unstable angina, congestive heart failure (NYHA > class II), uncontrolled hypertension
8. History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year
9. History of venous thrombosis that currently requires anti-coagulation therapy
10. Received IL-11 within 4 weeks of the first dose of investigational product
11. Receipt of G-CSF, peg-G-CSF, or GM-CSF within 4 weeks of the first dose of investigational product
12. Planned receipt of peg-G-CSF or GM-CSF after the first dose of investigational product
13. Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. The sponsor recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as 2 methods of contraception, for example 2 actual barrier methods, or 1 actual barrier method and 1 hormonal method.
14. Known hypersensitivity to any recombinant E coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune)
15. Inability to comply with study procedures.
16. Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s)
17. Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.

E.5 End points

E.5.1

Primary end point(s)

• Hematologic improvement of platelets (HI-P) after 4 months on therapy

E.5.1.1

Timepoint(s) of evaluation of this end point

after 4 months on therapy

E.5.2

Secondary end point(s)

• Cumulative hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophils (HI-N)
• The incidence of disease progression to higher stage MDS or AML
• Increase of peripheral blasts during therapy
• Association of the presence of certain mutations with disease progression in a retrospective analysis
• Incidence of bleeding events
• Type, incidence and severity of all adverse events including clinically significant changes in laboratory values

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study for all patients

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

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

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

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

Yes

E.8.1.7.1

Other trial design description

each patient receives IMP (Romiplostim), patients are stratified into 3 groups

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

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

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

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:

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)

After conclusion of the clinical trial, patients will receive further standard medical care as usual for this kind of disease.

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

2014-11-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-07-01

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