Clinical Trials Register

Summary
EudraCT Number:	2020-005553-24
Sponsor's Protocol Code Number:	SN-SPAS-201
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-05-10
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-005553-24

A.3

Full title of the trial

A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Treatment Efficacy and Safety Study of MYOBLOC® in the Treatment of Adult Upper Limb Spasticity Followed by an Open-Label
Extension, Multiple-Treatment Safety Study of MYOBLOC®

A.3.1

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

An Efficacy and Safety Study of MYOBLOC® in the Treatment of Adults with condition called “spasticity” (or tightness in the arm muscles) making it difficult to use arms and followed by an Open-Label Multiple-Treatment Safety Study

A.4.1

Sponsor's protocol code number

SN-SPAS-201

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	Solstice Neurosciences, LLC, a subsidiary of MDD US Operations, LLC
B.1.3.4	Country	United States
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	Solstice Neurosciences, LLC, a subsidiary of MDD US Operations, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Solstice Neurosciences, LLC, a subsidiary of MDD US Operations, LLC
B.5.2	Functional name of contact point	Tami Martin
B.5.3	Address:
B.5.3.1	Street Address	9715 Key West Avenue,
B.5.3.2	Town/ city	Rockville,
B.5.3.3	Post code	MD 20850
B.5.3.4	Country	United States
B.5.4	Telephone number	(301) 838-2607
B.5.5	Fax number	(240) 403-0065
B.5.6	E-mail	tmartin@supernus.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	NeuroBloc 5000 U/ml solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Sloan Pharma S.à.r.l.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	RimabotulinumtoxinB
D.3.9.1	CAS number	93384-44-2
D.3.9.3	Other descriptive name	BOTULINUM TOXIN TYPE B
D.3.9.4	EV Substance Code	SUB12472MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5000
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

Upper Limb Spasticity

E.1.1.1

Medical condition in easily understood language

A condition called “spasticity” ( or tightness in the arm muscles) in one of the arms, making it difficult to use arms.

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.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this trial is to assess the efficacy of MYOBLOC versus placebo in the treatment of adult upper limb spasticity.

E.2.2

Secondary objectives of the trial

The secondary objectives of this trial are:
• To establish a dose response between 2 active doses of MYOBLOC versus placebo.
• To assess the duration of therapeutic response after a single administration of MYOBLOC.
• To evaluate the long-term safety and tolerability of MYOBLOC after multiple administrations at approximately 13-week intervals over a minimum duration of 1 year.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible for participation, subjects with limb spasticity must meet all of the following criteria:
1. Able to understand the potential risks and benefits, the study requirements, and provide written informed consent before enrollment into the study; or if unable, the subject’s Legally Authorized Representative (LAR) may provide written informed consent.
2. Male or female ≥18 to maximum of 80 years of age, inclusive
3. Upper limb spasticity due to stroke, or traumatic brain injury, or spinal cord injury that occurred ≥ 6 months prior to randomization. Eligible subjects may have upper limb monoplegia or hemiplegia. Subjects with cerebral palsy are eligible for study enrollment.
4. Modified Ashworth Scale (MAS) scores of ≥2 in at least two muscle groups inclusive of the elbow, wrist, and finger flexors at screening and baseline.
5. In the Investigator’s opinion, the subject will be available and able to comply with the study
requirements for at least 1 year, based on the subject’s overall health and disease prognosis.
6. In the Investigator’s opinion, the subject will be willing and able to comply with all requirements of the protocol, including completion of study questionnaires. A caregiver may be designated to assist with the physical completion of questionnaires/scales.

E.4

Principal exclusion criteria

Subjects who meet any of the following criteria will not be allowed to participate:
1. Quadriplegia/tetraplegia, or triplegia with both upper limbs affected.
2. Uncontrolled epilepsy or any type of seizure disorder with a seizure(s) within the previous year.
3. Neuromuscular disorders including, but not limited to, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), multiple sclerosis (MS), myasthenia gravis, or muscular dystrophy.
4. History of major joint contracture(s), in which, based on the Investigator’s assessment, the contracture(s) significantly contributes to joint immobility in the affected upper limb.
5. Unresolved fracture(s) in the affected upper limb.
6. Severe atrophy in the affected upper limb.
7. Known hypersensitivity to botulinum toxins type A or B or to any MYOBLOC solution components.
8. Concomitant use or exposure within 5 half-lives of randomization of the following: aminoglycoside antibiotics, curare-like agents, or other agents that may interfere with neuromuscular function.
9. Treatment with a neurolytic agent (e.g., phenol, alcohol blocks) to the affected upper limb within 1 year before randomization.
10. Presence of a spinal stimulator or intrathecal baclofen pump that has not been turned off within 30 days prior to screening.
11. Changes to treatment regimen or any new treatment with oral antispasmodics and/or muscle relaxants within 30 days prior to randomization.
12. Initiation of physical and/or occupational therapy <30 days before randomization. Subjects receiving physical and/or occupational therapy ≥30 days before randomization must be willing to maintain their therapy regimen through Week 4 of the DBP.
13. Prior botulinum toxin type A (BoNT/A) or B (BoNT/B) treatment in the affected upper limb within 24 weeks before screening. Prior BoNT/A or BoNT/B treatment in areas other than the affected upper limb is not exclusionary but must have occurred at least 12 weeks before screening. Prior toxin exposure must have been well tolerated and without any significant long term side effects in the case of repeated prior exposure.
14. Subjects should not receive nor have any plans to receive any botulinum toxin treatment, other than the study drug (MYOBLOC), from the time that informed consent is obtained until participation in the study is complete.
15. Severe dysphagia (i.e., inability to swallow liquids, solids or both without choking or medical intervention), or dysphagia with a history of aspiration pneumonia, within 6 months before screening.
16. Has one or more screening clinical laboratory test values outside the reference range that, in the opinion of the Investigator, are clinically significant, or any of the following :
- Serum creatinine >1.5 times the upper limit of normal (ULN);
- Serum total bilirubin > 1.5 times ULN;
- Serum alanine aminotransferase or aspartate aminotransferase >2 times ULN.
17. Has any of the following cardiac findings at screening:
- Abnormal ECG that is, in Investigator’s opinion/evaluation, clinically significant;
- PR interval >220 ms;
- QRS interval >130 ms;
- QTcF interval >450 ms (for men), or >470 ms (for women) (QT corrected using
Fridericia’s method);
- Second-or third-degree atrioventricular block;
- Any rhythm, other than sinus rhythm, that is interpreted or assessed by the Investigator to be clinically significant.
Please refer to Protocol for full list of exclusion criteria

E.5 End points

E.5.1

Primary end point(s)

Co-Primary Efficacy Endpoints
Phase 2 and Phase 3 of the Double-Blind Period
• Change from baseline in tone of the PTMG selected for treatment as measured by the MAS at Week 4 post-injection.
• Clinical Global Impression of Change (CGI-C) in functional ability at Week 4 post-injection.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 4 post-injection

E.5.2

Secondary end point(s)

Phase 2 and Phase 3 of the Double-Blind Period
Change from baseline at Week 4 post-injection in:
• Tone in each muscle group selected for treatment as measured by the MAS
• Patient Global Impression of Change (PGI-C) • Caregiver Global Impression of Change (GGI-C)
• Pain Numeric Rating Scale (Pain-NRS) • Modified Barthel Index (MBI)
• Responder rate, defined as the percent of subjects with ≥1 grade reduction in their MAS score compared to their baseline score at Week 4 in the PTMG

Change from baseline at Weeks 2, 8, and 13 and if applicable, at reevaluation visits in:
• Tone in the PTMG as measured by the MAS
• Tone in each muscle group selected for treatment as measured by the MAS
• Duration of response by measuring the time elapsed between the injection and relapse of spasticity (MAS ≥2)
• CGI-C and Clinical Global Impression of Severity (CGI-S)
• PGI-C and Patient Global Impression of Severity (PGI-S)
• GGI-C and Caregiver Global Impression of Severity (GGI-S)
• Pain-NRS
• MBI (Week 2, Week 8, and end visit of the DBP only)

Open-Label Extension
• Duration of response by measuring the time elapsed between the injection and relapse of spasticity (MAS ≥2)

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to response in Q E.5.2 for timepoints

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

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)

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)

Yes

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

randomized, double-blind, placebo-controlled followed by open-label extension

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

Russian Federation

United States

Czechia

Hungary

Poland

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

Last Patient Last Visit

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:

232

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

158

F.4.2.2

In the whole clinical trial

272

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)

None

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

2021-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-02-13

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