Clinical Trials Register

Summary
EudraCT Number:	2017-000397-10
Sponsor's Protocol Code Number:	DSC/14/2357/51
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-03-15
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

UK - MHRA

A.2

EudraCT number

2017-000397-10

A.3

Full title of the trial

Open label, long-term safety, tolerability, and efficacy study of GIVINOSTAT in all DMD patients who have been previously treated in one of the GIVINOSTAT studies.

A.3.1

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

Study in which all the patients take the same investigational drug with the
aim of evaluate the long-term safety, tolerability, and efficacy of
GIVINOSTAT in all the patients affected with Duchenne Muscolar Dystrophy
who have been already treated in one of the GIVINOSTAT studies in the
past

A.3.2

Name or abbreviated title of the trial where available

Givinostat DMD long term study

A.4.1

Sponsor's protocol code number

DSC/14/2357/51

A.5.4

Other Identifiers

Name:

IND

Number:

126598

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	ITALFARMACO S.p.A.
B.5.2	Functional name of contact point	Clinical Research and Development
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	+39 02 64431
B.5.5	Fax number	+39 02 64433554
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/3/12/1009
D.3 Description of the IMP
D.3.1	Product name	GIVINOSTAT (hyrochloride monohydrate)
D.3.2	Product code	ITF2357
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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 (hydrochloride monohydrate)
D.3.9.1	CAS number	732302-99-7
D.3.9.2	Current sponsor code	ITF2357
D.3.9.3	Other descriptive name	GIVINOSTAT
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Duchenne Muscular Dystrophy (DMD)

E.1.1.1

Medical condition in easily understood language

Duchenne Muscular Dystrophy (DMD) is A neuromuscular disease characterized by rapidly progressive muscle
weakness and wasting

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10013801
E.1.2	Term	Duchenne muscular dystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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

To assess the long term safety and tolerability of GIVINOSTAT oral suspension in patients with Duchenne Muscular Dystrophy (DMD) following core protocols program.

E.2.2

Secondary objectives of the trial

To evaluate the effects of long-term administration of GIVINOSTAT on muscular function and strength;
To evaluate the effects of long-term administration of GIVINOSTAT on respiratory function;
To evaluate the impact on daily activities and quality of life following long-term administration of GIVINOSTAT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To clarify A.15 Answer:
Male subjects affected by Duchenne Muscular Dystrophy previously enrolled in one of the other DMD GIVINOSTAT studies (e.g DSC/14/2357/43, DSC/14/2357/48 and DSC/14/2357/50), aged ≥7 years and 6 months

INCLUSION CRITERIA:
1. Must have participated in one of the previous studies with
GIVINOSTAT in DMD and have attended the End of Study Visit;
2.Aged ≥7 years and 6 months old
3. Are able to give informed assent and/or consent in writing signed by
the subject and/or parent/legal guardian (according to local
regulations);
4. Subjects must be willing to use adequate contraception:
Contraceptive methods must since the previous GIVINOSTAT study
through 3 months after the last dose of study drug, and include the
following:
True abstinence (absence of any sexual intercourse), when in line with
the preferred and usual lifestyle of the subject. Periodic abstinence (e.g.
calendar, ovulation, symptothermal, postovulation methods) and
withdrawal are not acceptable methods of contraception.
oCondom with spermicide and the female partner must use an acceptable method of contraception, such as an oral, transdermal,
injectable or implanted steroid-based contraceptive, or a diaphragm or a
barrier method of contraception in conjunction with spermicidal jelly
such as for example cervical cap with spermicide jelly.

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will NOT be eligible for enrolment into the trial:

Subjects presenting with any of the following criteria will not be
included in the study:
1. Use of any pharmacologic treatment, other than corticosteroids, that
might have had an effect on muscle strength or function within 3 months
prior to be enrolled in this study (e.g., growth hormone); Vitamin D,
calcium, and any other supplements will be allowed;
2. Use of any current investigational drug other than Givinostat;
3. Have presence of other clinically significant disease, which, in the
Investigator's opinion, could adversely affect the safety of the subject,
making it unlikely that the course of treatment or follow-up would be
completed, or could impair the assessment of study results;
4. Have a diagnosis of other uncontrolled neurological diseases or
presence of relevant uncontrolled somatic disorders that are not related
to DMD;
5. Have platelets count, White Blood Cell and Hemoglobin at screening <
Lower Limit of Normal (LLN) (for abnormal screening laboratory test
results (<LLN), the platelets count, White Blood Cell and Hemoglobin will
be repeated once; if the repeat test result is still <LLN, then
exclusionary);
6.Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at
screening visit* (for abnormal screening laboratory test results (>ULN),
the triglycerides will be repeated once; if the repeat test result is still
>ULN, then exclusionary);
7.Have inadequate renal function, as defined by serum Cystatin C >2 x
the upper limit of normal (ULN) at screening visit*. If the value is >2 x
ULN, the serum Cystatin C will be repeated once; if the repeated test
result is still >2 x ULN, the subject should be excluded);
8. Have heart failure (New York Heart Association Class III or IV)
9. Have a current liver disease or impairment, including but not limited
to an elevated total bilirubin(i.e. > 1.5 x ULN), unless secondary to
Gilbert disease or pattern consistent with Gilbert's;
10. Have a baseline QTcF >450 msec, (as the mean of 3 consecutive
readings 5 minutes apart) or history of additional risk factors for
torsades de pointes (e.g., heart failure, hypokalemia, or family history of
long QT syndrome);
11. Have a psychiatric illness/social situations rendering the potential
subject unable to understand and comply with the muscle function tests
and/or with the study protocol procedures.
12. Have any hypersensitivity to the components of study medication;
13. Have a sorbitol intolerance or sorbitol malabsorption, or have the
hereditary form of fructose intolerance.

E.5 End points

E.5.1

Primary end point(s)

Type, incidence, and severity of treatment related/not related AEs and
SAEs

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline through week 48 and then yearly till the end of the study

E.5.2

Secondary end point(s)

Secondary endpoints

For ambulant patients:
• Change from baseline in physical function as measured by 6MWT,
NSAA, Time function tests (e.g. time to rise from floor, time to climb 4-
stairs, time to 10m walk)(week 48 and then yearly till the end of the
study)
• Change from baseline in muscle strength (e.g. knee extension and
elbow flexion) as measured by HHM (week 48 and then yearly till the
end of the study)
• Time to major disease milestones (e.g. time to loss of ambulation).
For non-ambulant patients:
• Change in physical function from baseline in the Egen Klassifikation
(EK) score (week 48 and then yearly till the end of the study)
• Change in patient and/or parent/caregiver reports of activities of daily
living as measured by Barthel Index (week 48 and then yearly till the
end of the study
• Change in upper limbs muscle strength (week 48 and then yearly till
the end of the study) evaluated by handheld myometry (HHM)
For all patients:
• Change from baseline in physical function as measured by the
Performance of Upper Limb (PUL) and MFM (week 48 and then yearly till
the end of the study)
• Change from baseline in respiratory function (week 48 and then yearly
till the end of the study) (e.g. FVC, FEV1, PEF)
• Change in patient and/or parent/caregiver reports of quality of life as
measured by PedsQL (week 48 and then yearly till the end of the study),
• Time to major disease milestones (e.g. time to respiratory support
needed during the day, time to scoliosis surgery, time to death).

E.5.2.1

Timepoint(s) of evaluation of this end point

week 48 and then yearly till the end of the study, summary description can be found in study synopsis of protocol

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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)

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.8.1.7.1

Other trial design description

This is an open label, long-term safety, tolerability, and efficacy study of GIVINOSTAT

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

Canada

France

Germany

Italy

Netherlands

Spain

United Kingdom

United States

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. The end of the trial is defined as the date of the last visit of the last subject undergoing the trial.

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

Yes

F.1.1