Clinical Trials Register

Summary
EudraCT Number:	2021-001634-18
Sponsor's Protocol Code Number:	M602011072
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2022-01-19
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-001634-18

A.3

Full title of the trial

A prospective, randomized, double-blind, placebo-controlled, two-stage, multicenter study with an open-label extension period to investigate the efficacy and safety of NT 201 in the treatment of lower limb spasticity in children and adolescents with cerebral palsy

Prospektywne, randomizowane, prowadzone metodą podwójnie ślepej próby z grupą kontrolną otrzymującą placebo, dwuetapowe, wieloośrodkowe badanie z otwartą fazą kontynuacyjną, oceniające skuteczność i bezpieczeństwo preparatu NT 201 w leczeniu spastyczności kończyn dolnych u dzieci i młodzieży z porażeniem mózgowym

A.3.1

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

A clinical study to investigate the efficacy and safety of NT 201 in the treatment of lower limb spasticity in children and adolescents with cerebral palsy

Badanie kliniczne mające na celu zbadanie skuteczności i bezpieczeństwa stosowania NT 201 w leczeniu spastyczności kończyn dolnych u dzieci i młodzieży z mózgowym porażeniem dziecięcym

A.3.2

Name or abbreviated title of the trial where available

ELLIE (Evaluation of Lower Limb IncobotulinumtoxinA Efficacy)

A.4.1

Sponsor's protocol code number

M602011072

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	Merz Pharmaceuticals GmbH
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	Merz Pharmaceuticals GmbH
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	Merz Pharmaceuticals GmbH
B.5.2	Functional name of contact point	Public Disclosure Manager
B.5.3	Address:
B.5.3.1	Street Address	Eckenheimer Landstraße 100
B.5.3.2	Town/ city	Frankfurt am Main
B.5.3.3	Post code	60318
B.5.3.4	Country	Germany
B.5.6	E-mail	clinicaltrials@merz.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	Xeomin
D.2.1.1.2	Name of the Marketing Authorisation holder	Merz Pharmaceuticals GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	NT 201
D.3.2	Product code	NT 201
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	Botulinum-Toxin Type A
D.3.9.1	CAS number	93384-43-1
D.3.9.2	Current sponsor code	NT 201
D.3.9.3	Other descriptive name	CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE FROM 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	equal
D.3.10.3	Concentration number	200
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	Neurotoxin

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

Pediatric lower limb (LL) spasticity (SP) caused by cerebral palsy (CP)

Spastyczność kończyn dolnych u dzieci z mózgowym porażeniem dziecięcym.

E.1.1.1

Medical condition in easily understood language

Pediatric lower limb spasticity caused by cerebral palsy.

Spastyczność kończyn dolnych u dzieci z mózgowym porażeniem dziecięcym.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10041416
E.1.2	Term	Spasticity
E.1.2	System Organ Class	100000004852

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
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.1.2 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 demonstrate efficacy by showing superiority of NT 201 compared intra-individually to placebo in children and adolescents with LL SP caused by CP at week 4 to week 6 after a single injection.

E.2.2

Secondary objectives of the trial

To demonstrate the relevance of the effect of NT 201 compared to placebo in children and adolescents with LL SP caused by CP in terms of response rates in derived MAS score of plantar flexors at week 4 or week 6 after a single injection.

To demonstrate the relevance of the effect of NT 201 compared to placebo in children and adolescents with LL SP caused by CP assessed on a Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) at week 4 to week 6 after a single injection.

To demonstrate the relevance of the effect of NT 201 compared to placebo in children and adolescents with LL SP caused by CP assessed on a Goal Attainment Scale (GAS) at week 4 to week 6 after a single injection.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male and female subjects ≥ 2 to ≤ 17 years of age;
• Bilateral, symmetrical pes equinus due to LL SP caused by CP in subjects with any Gross Motor Function Classification System (GMFCS) level; and
• Identical MAS plantar flexor score of ≥ 2 for pes equinus clinical patterns in both legs at neutral ankle position and knee at maximum extension.

E.4

Principal exclusion criteria

• Pre-dominant forms of muscle hypertonia/hyperactivity other than LL SP (e.g., rigidity, dystonia, dyskinesia);
• Previous treatment with Botulinum neurotoxin (BoNT) of any serotype in any body region within the last four months before injection at baseline visit; and
• Fixed contracture in at least one of both pes equinus.
• Significant involuntary movements or limitations that hinder MAS assessment or positioning.
• Clinically significant SP in LL clinical patterns other than pes equinus; or gait patterns drop foot, crouch gait, and equinus with jump knee.
• Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage greater than 30°.

E.5 End points

E.5.1

Primary end point(s)

Change in derived modified Ashworth Scale (MAS) score of plantar flexors from baseline at control visits at week 4 and week 6.

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to week 4 and 6

E.5.2

Secondary end point(s)

Secondary End Point 1:
Response in derived MAS score of plantar flexors at control visits at week 4 or week 6 with response defined as improvement of at least 1 point on the derived MAS score as compared to study baseline.
Secondary End Point 2:
GICS-PF score at control visits at week 4 and week 6 by investigator.
Secondary End Point 3:
GAS T-score at control visits at week 4 and week 6.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary End Point 1: From baseline to week 4 or week 6
Secondary End Point 2: Week 4 and week 6
Secondary End Point 3: Week 4 and week 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

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Intra-individual design

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

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

Poland

Russian Federation

Ukraine

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:

130

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:

104

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.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children and adolescents (also institutionalised or mentally handicapped) will be enrolled, which are legally unable of giving their consent personnally.

Do badania zostaną włączone dzieci i młodzież (również zinstytucjonalizowane lub upośledzone umysłowo), które zgodnie z prawem nie są w stanie osobiście wyrazić zgody.

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

130

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)

No specific post-study arrangements are made, and no specific post-study care will be performed after this study.

The subject and the parent(s) may consult his/her physician for treatment options, and receive antispastic medication including, e.g., BoNT treatment, alcohol, phenol injections as well as physiotherapy, orthotic management, and any other rehabilitation treatment at the investigator’s discretion. This also applies to subjects who discontinue the study prematurely.

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

2022-09-07

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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