Clinical Trials Register

Summary
EudraCT Number:	2014-002539-32
Sponsor's Protocol Code Number:	The_WE-Study
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:	2018-10-17
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2014-002539-32

A.3

Full title of the trial

The WE-Study - Walking Easier with cerebral palsy

Badanie Kliniczne WE - Łatwiejsze Chodzenie z Porażeniem Mózgowym

A.3.1

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

The WE-Study - Walking Easier with cerebral palsy

Badanie Kliniczne WE - Czy toksyna botulinowa (Botoks) ułatwia chodzenie u dzieci z mózgowym porażeniem dziecięcym?

A.4.1

Sponsor's protocol code number

The_WE-Study

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	St. Olavs University Hospital
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	xxx
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	St Olavs Hospital
B.5.2	Functional name of contact point	NorCRIN
B.5.3	Address:
B.5.3.1	Street Address	PO box 3250
B.5.3.2	Town/ city	Trondheim
B.5.3.3	Post code	7006
B.5.3.4	Country	Norway
B.5.4	Telephone number	0047826000
B.5.6	E-mail	post.ort.rev.hud@stolav.no

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	Botox
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals Ireland Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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 and solvent 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	onabotulinumtoxin A
D.3.9.3	Other descriptive name	CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS
D.3.9.4	EV Substance Code	SUB26174
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	up to
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	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	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

cerebral palsy

Mózgowe porażenie dziecięce

E.1.1.1

Medical condition in easily understood language

cerebral palsy

Mózgowe porażenie dziecięce

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10021740
E.1.2	Term	Infantile cerebral palsy
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate whether injections of BoNT-A in the calf muscles (mm. gastrocnemius and soleus) make walking easier in children with cerebral palsy within a time span of 6 months.

Ocenienie, czy wstrzyknięcie BoNT-A do mięśni łydki (mięsień brzuchaty i płaszczkowaty) ułatwia chodzenie dzieciom/nastolatkom z porażeniem mózgowym w okresie 6 miesięcy

E.2.2

Secondary objectives of the trial

To evaluate whether an improvement in energy cost during walking is associated with less pain, increased daily activity and perceived improved performance and satisfaction.

Ocenienie, czy poprawa wydatku energetycznego podczas chodzenia jest powiązana ze zwiększeniem aktywności dziennej, mniejszym bólem i poprawą wydajności subiektywnej oraz satysfakcji

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Eligible to participate in the study are children and adolescents with spastic cerebral palsy referred to the out-patient clinics at the participating sites and regional partners, for injection of BoNT-A in the calf muscles.
All of the following conditions must apply to the prospective patient at screening prior to receiving study agent (e.g.):
• Diagnosed with unilateral or bilateral CP in their medical record
• GMFCS level I and II
• Age range 4-17.
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Do udziału w badaniu kwalifikują się dzieci i młodzież ze spastycznym mózgowym porażeniem dziecięcym, kierowane do poradni w uczestniczących ośrodkach i regionalnych partnerach, celem jednostronnego lub obustronnego jednokrotnego wstrzyknięcia BoNT-A w mięśnie łydek (iniekcje do kończyn górnych mogą być zastosowane).
Wszystkie poniższe warunki muszą być spełnione u przyszłego pacjenta podczas badania przesiewowego przed przyjęciem badanego leku:
- Zdiagnozowane jednostronne lub obustronne mózgowe porażenie dziecięce w wywiadzie medycznym
- Poziom I lub II zgodnie z systemem klasyfikacji funkcji motoryki dużej (Gross Motor Function Classification System – GMFCS) [1].
- Zakres wiekowy: 4–17 lat
- Podpisana świadoma zgoda i oczekiwana współpraca pacjentów w celu leczenia i obserwacji musi być uzyskana i udokumentowana zgodnie z ICH GCP i przepisami krajowymi / lokalnymi.

E.4

Principal exclusion criteria

Patients will be excluded from the study if they meet any of the following criteria:
• BoNT-A injections in the lower limbs in the last 6 months before intervention
• History of adverse reactions to BoNT-A
• Known hypersensitivity to BoNT-A or to any of the excipients
• Orthopedic surgery in the lower limbs in the last 2 years
• Major cognitive impairments (must be able to take verbal instructions and conduct the test procedure)
• Presence of infection at the proposed injection site(s)
• Subclinical or clinical evidence of defective neuromuscular transmission e.g. myasthenia gravis or Lambert-Eaton Syndrome in patients with peripheral motor neuropathic diseases (e.g. amyotrophic lateral sclerosis or motor neuropathy) or other underlying neurological disorders that may be affected by BoNT-A injections
• Pregnant or breast-feeding
• Childbearing potential not using contraception
• Any reason why, in the opinion of the investigator, the patient should not participate
• Children in need for deep sedation under treatment. Children receiving concurrent injections in the upper limbs where deep sedation is standard procedure, are not excluded

Pacjenci zostaną wykluczeni z badania, jeśli spełnią którekolwiek z poniższych kryteriów:
- Iniekcje z BoNT-A do kończyn dolnych w ciągu 6 ostatnich miesięcy
- Reakcje niepożądane na BoNT-A w wywiadzie (jeśli dotyczy)
- Operacja ortopedyczna kończyn dolnych w ciągu ostatnich 2 lat
- Poważne upośledzenie funkcji poznawczych (pacjent musi być w stanie wypełniać polecenia słowne i przeprowadzić procedurę badania)
- Obecność infekcji w proponowanych miejscach iniekcji
- Subkliniczne lub kliniczne dowody na występowanie zaburzeń przewodnictwa nerwowo-mięśniowego, np. miastenia rzekomoporaźna lub zespół Lamberta-Eatona u pacjentów z obwodowymi neuropatycznymi schorzeniami ruchowymi (np. stwardnieniem zanikowym bocznym lub neuropatią ruchową ) lub innymi istniejącymi schorzeniami, na które mogą mieć wpływ iniekcje z BoNT-A
- Ciąża lub karmienie piersią
- Możliwość zajścia w ciążę i niestosowanie antykoncepcji
- Każdy powód, który zdaniem badacza wyklucza pacjenta z badania
- Dzieci wymagające wykonywania iniekcji w głębokim znieczuleniu. Dzieci leczone równocześnie iniekcjami do kończyn górnych, gdzie głębokie znieczulenie jest procedurą standardową, nie są wykluczone.

E.5 End points

E.5.1

Primary end point(s)

energy cost during walking, measured during a 5-minutes submaximal Walk Test (5MWT) at a self-chosen velocity with simultaneous gas-exchange measurements

wydatek energetyczny podczas chodzenia, mierzony podczas 5-minutowego submaksymalnego testu chodu (5MWT) z samodzielnie dobraną prędkością z jednoczesnymi pomiarami wymiany gazowej

E.5.1.1

Timepoint(s) of evaluation of this end point

at baseline, 4, 12, 24 weeks

wyjściowo, 4, 12, 24 tygodnie

E.5.2

Secondary end point(s)

1. Habitual activity, measured by a body worn accelerometer over a period of 7 consecutive days during three time periods.
2. Mobility, measured by the Functional Mobility Scale (FMS). Through an interview, the FMS measures mobility over three distinct distances in order to represent mobility at home (5 meters), at school (50 meters) and in the wider community (500 meters) (30). The FMS captures walking performance or what the child usually does in his/her usual environment.
3. Perceived change in performance and satisfaction, measured by the Canadian Occupational Performance Measure (COPM). The COPM is used to detect changes in self-perceived activity performance in the areas of self-care, productivity (i.e., school), and leisure. The instrument is administered as semi-structured interviews that focuses on activities that the participants want, need, or are expected to perform.
4 Recurrent musculoskeletal pain, measured by the two questions on pain from Child Health Questionnaire (Norwegian version) and elements from Brief Pain Inventory
5 Fatiguability measured by the OMNI rating of perceived exertion scale (OMNI-RPE)

1. Zwykła aktywność, mierzona za pomocą akcelerometru na ciele przez 7 kolejnych dni w trzech okresach.
2. Mobilność mierzona Skalą Mobilności Funkcjonalnej (FMS). Poprzez wywiad FMS mierzy mobilność na trzech różnych dystansach, aby reprezentować mobilność w domu (5 metrów), w szkole (50 metrów) i w szerszej społeczności (500 metrów) (30). FMS rejestruje chodzenie lub to, co dziecko zwykle robi w swoim zwykłym otoczeniu.
3. Postrzegana zmiana w wydajności i satysfakcji, mierzona przez Kanadyjski Wskaźnik Efektywności Zawodowej (COPM). COPM służy do wykrywania zmian w postrzeganiu własnej aktywności w obszarach samopomocy, wydajności (np. szkoła) i wypoczynku. Instrument jest zarządzany w formie częściowo ustrukturyzowanych wywiadów, które koncentrują się na działaniach, które uczestnicy chcą, potrzebują lub mają wykonać.
4. Nawracające bóle mięśniowo-szkieletowe mierzone dwoma pytaniami dotyczącymi bólu z Kwestionariusza Zdrowia Dziecka (wersja norweska) i elementami z Brief Pain Inventory
5. Męczliwość mierzona oceną OMNI w postrzeganej skali wysiłkowej (OMNI-RPE)

E.5.2.1

Timepoint(s) of evaluation of this end point

at baseline, 4, 12, 24 weeks

wyjściowo, 4, 12, 24 tygodnie

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

Yes

E.6.4

Safety

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

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

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:

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.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

Standard Of Care

Standardowa opieka

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

2019-02-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-12-31

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