Clinical Trials Register

Summary
EudraCT Number:	2013-000860-27
Sponsor's Protocol Code Number:	DSC/12/2357/45
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-04-29
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2013-000860-27

A.3

Full title of the trial

A two-part study to assess the safety and preliminary efficacy of Givinostat in patients with JAK2V617F positive Polycythemia Vera

A.3.1

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

A two-part study to investigate the safety and preliminary efficacy of Givinostat in patients with Polycythemia Vera

A.4.1

Sponsor's protocol code number

DSC/12/2357/45

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	ITALFARMACO S.p.A
B.1.3.4	Country	Italy
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	ITALFARMACO S.p.A
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Italfarmarmaco S.p.A.
B.5.2	Functional name of contact point	Paolo Bettica
B.5.3	Address:
B.5.3.1	Street Address	Via dei Lavoratori, 54
B.5.3.2	Town/ city	Cinisello Balsamo (MI)
B.5.3.3	Post code	20092
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39026443 2584
B.5.5	Fax number	+39026443 3554
B.5.6	E-mail	p.bettica@italfarmaco.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	EU/3/09/719
D.3 Description of the IMP
D.3.1	Product name	Givinostat
D.3.2	Product code	ITF2357
D.3.4	Pharmaceutical form	Capsule, hard
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	GIVINOSTAT
D.3.9.3	Other descriptive name	ITF2357
D.3.9.4	EV Substance Code	SUB30834
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	50
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.IMP: 2
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	EU/3/09/719
D.3 Description of the IMP
D.3.1	Product name	Givinostat
D.3.2	Product code	ITF2357
D.3.4	Pharmaceutical form	Capsule, hard
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	GIVINOSTAT
D.3.9.3	Other descriptive name	ITF2357
D.3.9.4	EV Substance Code	SUB30834
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	100
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

JAK2V617F positive Polycythemia Vera

E.1.1.1

Medical condition in easily understood language

Disorder of the bone marrow in which excess blood cells are produced

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10036061
E.1.2	Term	Polycythemia vera
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

Part A
• To characterize the safety, tolerability and MTD of Givinostat in patients with PV.

Part B
• To evaluate the preliminary efficacy of Givinostat at the MTD after 3 cycles.
• To determine the safety and tolerability of Givinostat at the MTD after 3 cycles.

E.2.2

Secondary objectives of the trial

Part A
• To evaluate the preliminary efficacy of Givinostat after 3 and 6 cycles of treatment.
• To characterize PK.

Part B
• To evaluate the preliminary efficacy of Givinostat at the MTD after 6 cycles.
• To determine the safety and tolerability of Givinostat at the MTD after 6 cycles.
• To characterize PK.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must be able to provide informed consent and be willing to sign an informed consent form;

2. Patients must have an age ≥18 years;

3. Patients must have a confirmed diagnosis of PV according to the revised WHO criteria;

4. Patients must have JAK2V617F positive disease;

5. Patients must have an active/not controlled disease defined as
a) HCT ≥ 45% or HCT <45% in need of phlebotomy, and
b) PLT counts > 400 x109/L, and
c) WBC > 10 x109/L;

Note that if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may be expanded to all patients with cMPN. In this case, the inclusion criteria 5 will be modified as following only for Part A:
5. Patients must have an active/not controlled disease defined as:
a) ET patients: PLT counts > 600 x109/L;
b) MF patients: no response according to EUMNET criteria.

6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 in Part A, ECOG performance status ≤ 2 in Part B within 7 days of initiating study drug;

7. Female patient of childbearing potential has a negative serum or urine pregnancy test within 72 hours of the first dose of study therapy; please note that a borderline urine pregnancy test must be followed with a serum pregnancy test;

8. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential;

9. Adequate and acceptable organ function within 7 days of initiating study drug;

10. Willingness and capability to comply with the requirements of the study.

E.4

Principal exclusion criteria

1. Active bacterial or mycotic infection requiring antimicrobial treatment;

2. Pregnancy or nursing;

3. A clinically significant QTc prolongation at baseline (e.g. repeated demonstration of a QTc interval ≥ 450 msec);

4. Use of concomitant medications known to prolong the QT/QTc interval;

5. Clinically significant cardiovascular disease including:
a) Uncontrolled hypertension despite medical treatment, myocardial infarction, unstable angina within 6 months from study start;
b) New York Heart Association (NYHA) Grade II or greater congestive heart failure;
c) History of any cardiac arrhythmia requiring medication (irrespective of its severity);
d) A history of additional risk factors for TdP (e.g. heart failure, hypokalemia, family history of Long QT Syndrome);

6. Known positivity for HIV;

7. Known active HBV and/or HCV infection;

8. Platelet count < 100 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);

9. Absolute neutrophil count < 1.2x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);

10. Serum creatinine > 2 xULN;

11. Total serum bilirubin > 1.5 xULN except in case of Gilbert’s disease;

12. Serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 x ULN;

13. History of other diseases (including active tumours), metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications;

14. Prior treatment with a JAK2 or HDAC inhibitor or participation in an interventional clinical trial for cMPN, including PV, ET or MF;

15. Systemic treatment for cMPN other than aspirin/cardio aspirin;
16. Hydroxyurea within 28 days before enrolment (i.e. the receipt of the Patient ID);

17. Interferon alpha within 14 days before enrolment (i.e. the receipt of the Patient ID);

18. Anagrelide within 7 days before enrolment (i.e. the receipt of the Patient ID);

19. Any other investigational drug or device within 28 days before enrolment (i.e. the receipt of the Patient ID);

20. Patient with known hypersensitivity to the components of study therapy.

E.5 End points

E.5.1

Primary end point(s)

Part A
• Safety and tolerability evaluated as following:
- Number of patients experiencing adverse events;
- Type, incidence, and severity of treatment-related adverse events, graded according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.03, 14th June 2010).
• Determination of the MTD of Givinostat based on cycle 1 DLT’s.

Part B
• Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 3 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet (ELN) response criteria.
• Safety and tolerability of Givinostat at the MTD after 3 cycles evaluated as following:
- Number of patients experiencing adverse events;
- Type, incidence, and severity of treatment-related adverse events, graded according to CTCAE v. 4.03.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A
Safety - ongoing
MTD - cycle 1

Part B
After 3 cycles

E.5.2

Secondary end point(s)

Part A
• Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 3 and 6 cycles; the response will be evaluated according to the clinico-haematological ELN response criteria.
• Individual Givinostat concentrations tabulated by dose cohort along with descriptive statistics.
Part B
• Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 6 cycles; the response will be evaluated according to the clinico-haematological ELN response criteria.
• Safety and tolerability of Givinostat at the MTD after 6 cycles evaluated as following:
- Number of patients experiencing adverse events;
- Type, incidence, and severity of treatment-related adverse events, graded according to CTCAE v. 4.03.
• Individual Givinostat concentrations tabulated with descriptive statistics.

E.5.2.1

Timepoint(s) of evaluation of this end point

Part A
cycle 3 and cycle 6

Part B
Cycle 6

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

Yes

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase 1b/2

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

LPLV

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:

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)

Patients achieving clinical benefit will be allowed to continue treatment with Givinostat (at the same dose and schedule) in a long-term study (Study N.: DSC/11/2357/44)

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

2013-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-09-25

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