ICH GCP - EU Clinical trials Registry - 2009-017709-12 (PL)

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Summary
EudraCT Number:	2009-017709-12
Sponsor's Protocol Code Number:	Y-55-52120-141
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-01-30
Trial results	Removed from public view

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

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2009-017709-12

A.3

Full title of the trial

A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, PLACEBO CONTROLLED STUDY ASSESSING THE EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY

Wieloośrodkowe, prospektywne, kontrolowane placebo badanie fazy III z randomizacją i wykorzystaniem metody podwójnie ślepej próby, mające na celu ocenę skuteczności i bezpieczeństwa stosowania preparatu DYSPORT
w leczeniu spastyczności kończyn dolnych u dzieci z dynamiczną stopą końską w przebiegu mózgowego porażenia
dziecięcego.

A.3.1

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

A.4.1

Sponsor's protocol code number

Y-55-52120-141

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	Ipsen Pharma SAS
B.1.3.4	Country	France
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	Ipsen Pharma SAS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ipsen Pharma
B.5.2	Functional name of contact point	CT desk
B.5.3	Address:
B.5.3.1	Street Address	65 Quai Georges Gorse
B.5.3.2	Town/ city	Boulogne-Billancourt
B.5.3.3	Post code	92100
B.5.3.4	Country	France
B.5.4	Telephone number	+33 (0)158 33 50 00
B.5.5	Fax number	+33 (0)158 33 50 01
B.5.6	E-mail	ct-application@ipsen.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	Yes
D.2.1.1.1	Trade name	Dysport
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen Biopharm limited
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CLOSTRIDIUM BOTULINUM TOXIN TYPE A
D.3.9.1	CAS number	93384-43-1
D.3.9.3	Other descriptive name	BOTULINUM TOXIN TYPE A
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	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	Yes
D.3.11.13.1	Other medicinal product type	Toxin

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	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Lower limb spasticity in children with dynamic equinus foot deformity due to cerebral palsy.

E.1.1.1

Medical condition in easily understood language

Lower limb spasticity in children with dynamic equinus foot deformity due to cerebral palsy.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10024132
E.1.2	Term	Leg spasticity
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary study objective will be to assess the efficacy of Dysport compared to placebo at Week 4 on the mean change from baseline in ankle joint hypertonicity in children with dynamic equinus foot deformity associated with cerebral palsy (CP).

E.2.2

Secondary objectives of the trial

The secondary study objectives will include assessments of the efficacy of Dysport compared to placebo on global improvement as measured by the Physician’s Global Assessment (PGA), and on attainment of treatment goals as measured by the Goal
Attainment Scale (GAS).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must satisfy all of the following inclusion criteria to be eligible for the
study:
(1) Signed informed consent obtained from the child’s parent(s)/guardian(s) and a signed assent from the child when and where applicable.
(2) Be from 2 to 17 years of age, inclusive.
(3) Have a diagnosis of CP as defined by Rosenbaum.
(4) Be ambulatory with spastic hemiparesis, paraparesis, diparesis or tetraparesis characterised by an equinus foot positioning during the stance phase of the gait.
(5) Have ability to walk (sufficient to complete video 2D motion analysis) with or without walking aids.
(6) Have a MAS score ≥2 at the ankle joint of the (most) affected lower limb
to be injected.
(7) Have a spasticity grade (Y) between 2 and 4, inclusive on the TS assessed at the ankle joint of the most affected limb to be injected with a spasticity angle (X) of 10o or more.
(8) Be classified as GMFCS Level 1 to 3, inclusive.
(9) Botulinum toxin naïve subjects or subjects having received their last BTX treatment of any type more than six months prior to study entry for any condition.
(10) If undergoing pre-study physiotherapy, it must have begun at least one month prior to study start and be continued during the study at the same pre-study frequency and intensity (as well as maintaining the usual level of physical activity until the end of the study) up to at least the Week 12 visit.
(11) Be instructed and willing to use their casting/ orthoses in the same way as before entry into the study until the end of the Week 12 visit.

E.4

Principal exclusion criteria

Subjects are to be excluded if any of the following applies:
(1) Diagnosed as resistant to BTX treatment of any type.
(2) Evidence of non-ambulatory status.
(3) Major limitation in the passive range of motion at the ankle,
as defined by maximum ankle dorsiflexion measured by XV1
of <80° (Tardieu Scale angle) in the most affected leg to be
injected
(4) Subjects likely to be treated with BTX in the upper limbs during the course
of this double blind study.
(5) Severe athetoid or dystonic movements in the targeted lower limb(s).
(6) Significant difference (>2 cm) between the length of legs, defined
clinically and confirmed, as required, by scanogram.
(7) Current need for surgery or previous surgery for spasticity of
the GSC and/or hamstring muscles (and tendons) in the most
affected leg to be injected.
(8) Serial casting in the past 12 weeks.
(9)Previous injection of alcohol and/or phenol into the GSC
and/or hamstrings in the most affected leg to be injected.
(10) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics) or neuroblocking agents used during surgery (e.g. curare) within the last 30 days prior to study treatment.
(11) Be pregnant and/or lactating.
(12) Female subjects, not willing to use contraceptive measures throughout the course of the study if post-pubertal and sexually active.
(13) Inability or unwillingness to comply with the protocol.
(14) Subjects with any clinical (or sub-clinical) evidence of marked defective neuromuscular transmission (e.g. Lambert-Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders.
(15) Known sensitivity to BTX or to any of the components in the formulation or allergy to cow’s milk protein.
(16) An infection at the injection site(s).
(17) Ongoing treatment with intrathecal baclofen or previous/planned rhizotomy.
(18) Treatment with a new investigational drug within 30 days prior to enrolment into the study or are scheduled to receive such a drug during the study period.
(19) Any medical condition, laboratory or diagnostic procedure finding, which might compromise compliance with the objectives and procedures of this protocol or preclude administration of BTX-A, as judged by the Investigator.

E.5 End points

E.5.1

Primary end point(s)

Mean change from baseline to Week 4 in the MAS score at the ankle joint of the (most) affected lower limb.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 4

E.5.2

Secondary end point(s)

Mean PGA Score and Mean GAS score

E.5.2.1

Timepoint(s) of evaluation of this end point

week 4

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

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

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

Yes

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

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

Chile

Czech Republic

France

Mexico

Poland

Turkey

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

Last visit last subject

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

Number of subjects for this age range:

228

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)

Yes

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

A signed assent is obtained from the child when and where applicable (children from 2-year old can be included). Signed informed consent is always obtained from the child’s parent(s)/guardian(s).

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

100

F.4.2.2

In the whole clinical trial

228

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)

" Subjects who have completed; week 12, week 16, week 22 or week 28 follow-up visit will be offered entry into the open label extension study Y-55-52120-147.

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

2012-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-06-25

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