Clinical Trials Register

Summary
EudraCT Number:	2018-000001-23
Sponsor's Protocol Code Number:	DroSpas-1
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-16
Trial results	View 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

Czechia - SUKL

A.2

EudraCT number

2018-000001-23

A.3

Full title of the trial

A phase III, multi-centre, randomised, double-blind, placebo-controlled, parallel-group clinical trial to investigate the efficacy and safety of BX-1 for the symptomatic relief of spasticity in patients with multiple sclerosis

Multicentrické, randomizované, dvojitě zaslepené, placebem kontrolované klinické hodnocení v paralelních skupinách fáze III zkoumající účinnost a bezpečnost přípravku BX-1 při symptomatické léčbě spasticity u pacientů s roztroušenou sklerózou

A.3.1

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

Clinical study to investigate the efficacy and safety of the test substance BX-1 (dronabinol) for the symptomatic relief of spasticity in patients with multiple sclerosis

Klinické hodnocení zkoumající účinnost a bezpečnost hodnoceného přípravku BX-1 (dronabinol) při symptomatické léčbě spasticity u pacientů s roztroušenou sklerózou

A.3.2

Name or abbreviated title of the trial where available

BX-1 in spasticity due to MS

BX-1 u spasticity při RS

A.4.1

Sponsor's protocol code number

DroSpas-1

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	Bionorica SE
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	Bionorica SE
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	Bionorica SE
B.5.2	Functional name of contact point	Clinical Operations R&D
B.5.3	Address:
B.5.3.1	Street Address	Kerschensteinerstr. 11-15
B.5.3.2	Town/ city	Neumarkt
B.5.3.3	Post code	92318
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4991812317035
B.5.5	Fax number	+49918123167035
B.5.6	E-mail	drospas-1@bionorica.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	No
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	Dronabinol 25 mg/ml, oral drops
D.3.2	Product code	BX-1
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	No
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	Dronabinol
D.3.9.1	CAS number	1972-08-3
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Dronabinol
D.3.9.4	EV Substance Code	SUB06407MIG
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	25
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	Yes
D.3.11.13.1	Other medicinal product type	THC isolate ≥ 95.0%; herbal substance: Cannabis flos, totum is the starting material

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	Oral drops, solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Symptomatic relief of spasticity in patients with multiple sclerosis

E.1.1.1

Medical condition in easily understood language

Improvment of spasticity in patients with multiple sclerosis. Spasticity is a condition in which certain muscles are continuously contracted causing muscle stiffness.

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	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 objective of the trial is to demonstrate superiority of BX-1 over placebo by comparison of proportions of NRS-S responders between the two treatment groups.

E.2.2

Secondary objectives of the trial

To demonstrate improvement
1) in spasticity as measured with Numerical Rating Scale for Spasticity
2) in pain as measured with Numerical Rating Scale for Pain
3) in spasm frequency and severity as measured with Penn Spasm Frequency Scale
4) in walking ability as measured with Timed 25-Foot Walk Test
5) of the physical and psychological impact of multiple sclerosis as measured with Multiple Sclerosis Impact Scale–29 version 2
6) on quality of life as measured with Short-Form Health Survey of the Medical Outcomes Study Version 2
7) in sleep quality as measured with Numerical Rating Scale for Sleep Quality
8) in fatigue as measured with Numerical Rating Scale for Fatigue
9) in patient’s status as measured with Patient´s Global Impression of Change Scale and Clinical Global Impression – Improvement Scale
Safety objective is to evaluate the safety profile of BX-1 by assessing numbers of treatment emergent (serious) AEs, (serious) ARs, laboratory parameters, ECG and vital signs

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients aged 18 to 65 years
2. Presence of MS according to 2010 or 2017 revised McDonald criteria
3. Patients with stable MS for at least 3 months before enrolment in the opinion of the treating physician
Note: Patients with a MS relapse during 3 month prior to enrolment are not considered to have stable MS
4. Ongoing spasticity for at least 3 months before enrolment
5. Spasticity in at least 2 lower limb muscles
6. Expanded Disability Status Scale (EDSS) score ≥ 3.0 and ≤ 6.5
7. Previous treatment with at least two different optimized oral MS anti-spasticity therapies before inclusion. Both treatment attempts must include at least baclofen or oral tizanidine, which can be
combined with other anti-spasticity drugs.
AND
Patients currently receiving an optimized treatment corresponding to the last treatment attempt with stable dosage for at least 30 days prior to Visit 0.
Note: A treatment is optimized if, in the opinion of the investigator, it is the best efficient and the best tolerated dose in accordance with the available summary of product characteristics
8. Female patients of non-childbearing potential or if of childbearing
potential using highly effective contraceptive methods or double barrier contraception.
For men: no specific contraception methods need to be used
9. Willingness to follow the study procedure for the whole duration of the trial and signed informed consent at screening prior to any trial-related procedure

E.4

Principal exclusion criteria

1. Any present disease other than MS that could affect spasticity (e.g. traumatic brain injury, spinal cord injury, brain damage due to a lack of oxygen, stroke, encephalitis, meningitis)
2. Intake of not permitted concomitant medication prior to screen-ing and concomitant medication which should be unaltered prior to Visit 0 in an unstable dosage regimen (for details please refer to chapter concomitant/not permitted concomitant medication)
3. Significant fixed tendon contractures
4. History of epileptic seizures
5. History of or existing relevant CNS disorder (other than MS)
6. History of or existing relevant psychiatric disorders (e.g. schizophrenia, psychosis, manic disorders, severe depressive disorders, suicidal ideations, drug and/or alcohol abuse etc.)
7. Patients with a positive drug abuse screening test, except for medications used to treat a medical condition and reported as such by the patient; all patients with a positive result for cannabis/THC
8. History of or existing relevant cardiac diseases or pathological findings (e.g. chronic insufficiency NYHA III/IV, severe arrhythmia, unstable angina pectoris, myocardial infarction within the past 6 months, QT prolongation)
9. Known HIV, and/or active Hepatitis B or C infection
10. History of or existing malignancy during the past 5 years before screening except history of basal cell carcinoma and melanoma in situ
11.Significantly impaired renal function (estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73m2)
12.Significantly impaired hepatic function (Alanine Aminotransferase > 3 times upper limit of normal or bilirubin > 2 times upper limit of normal, except Gilbert syndrome)
13.Known allergic reactions to the active ingredients used or to constituents of the IMP
14.Chronic or active infection requiring a systemic therapy
15. Pregnancy, breastfeeding or planned pregnancy
16.Any condition that interferes with the participation in the clinical trial at the discretion of the investigator
17. Patients not able to follow study instructions, not able to follow the study assessments defined by the protocol, unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
18. Patients in custody by judicial or official order
19. Patients who are members of the staff of the trial centre, staff of the sponsor or CRO, the investigator him/herself or close relatives of the investigator
20. Parallel participation in another clinical trial, participation in another trial within less than 30 days or five half-lives of IMP (whatever is longer) to screening, or previous participation in this trial (except one time screening failures). A patient may be re-screened once, if any inclusion criterion is not met or any exclusion criterion is met during the first screening attempt.

E.5 End points

E.5.1

Primary end point(s)

Responder analysis: proportion of patients showing improvement in spasticity (change from baseline corresponding to the mean NRS-S score during 7 days prior to randomisation) of 18% or more in average NRS-S assessment at end of treatment (mean NRS-S score during 7 days prior to Visit 6).

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of the trial

E.5.2

Secondary end point(s)

Secondary efficacy endpoints:
1.Responder analysis: proportion of patients showing improvement in spasticity (change from baseline) of 30% or more in average NRS-S assessment at end of treatment (Visit 6)
2.Responder analysis: proportion of patients showing improvement in spasticity (change from baseline) of 50% or more in average NRS-S assessment at end of treatment (Visit 6)
3.Time to response: time to reach first improvement in spasticity (change from baseline) of 18% or more, based on patient’s daily spasticity assessment on the NRS-S
4.Time to response: time to reach first improvement in spasticity (change from baseline) of 30% or more, based on patient’s daily spasticity assessment on the NRS-S
5.Weekly mean of the patient’s daily spasticity assessments on the NRS-S during Visit 0 - Visit 6
6.Weekly mean of the patient’s daily pain assessments on the NRS-P during Visit 0 - Visit 6
7.Responder analysis: proportion of patients showing improvement in pain (change from baseline) of 15% or more in average NRS-P assessment at end of treatment (Visit 6)
8.Responder analysis: proportion of patients showing improvement in pain (change from baseline) of 30% or more in average NRS-P assessment at end of treatment (Visit 6)
9.Time to response: time to reach first improvement in pain (change from baseline) of 15% or more, based on patient’s pain assessment on the NRS-P
10. Time to response: time to reach first improvement in pain (change from baseline) of 30% or more, based on patient’s pain assessment on the NRS-P
11. Weekly mean of the patient’s daily spasm frequency and se-verity assessments on the PSFS during Visit 0 - Visit 6
12. Mean change from baseline of spasm frequency and severity assessments on the PSFS at end of treatment (Visit 6)
13. Mean change from baseline of Timed 25-Foot Walk (T25-FW) at Visit 4 and Visit 6
14. Responder analysis: proportion of patients showing improvement in TF25-FW (change from baseline) of 20% or more at Visit 6
15. Mean change from baseline of the physical and psychological impact of multiple sclerosis assessed with the Multiple Sclerosis Impact Scale– 29 version 2 (MSIS-29 v2) at Visit 4 and Visit 6
16. Mean change from baseline of quality of life measured with the Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Health (RE), and Mental Health (MH), the Physical Component Summary (PCS) and the Mental Component Summary (MCS) of SF-36 v2 at Visit 6
17. Mean change from baseline of sleep quality measured with the NRS-SQ at Visit 3 - Visit 6
18. Mean change from baseline of fatigue measured with the NRS-F at Visit 3 - Visit 6
19. Overall patients’ status measured by Patient´s Global Impression of Change scale (PGIC) at Visit 5 and Visit 6
20. Overall patients’ status measured by Clinical Global Impression – Improvement scale (CGI-I) at Visit 5 and Visit 6
Safety endpoints:
21. Nature (term) and frequency of treatment emergent adverse events (AEs), treatment emergent SAEs, adverse reactions (ARs) and SARs
22. AEs leading to discontinuation
23. Change from screening (Visit 0) in safety laboratory parameters (blood/urine) at end of treatment
24. Change from screening (Visit 0) in vital signs at end of treatment
25. Change from randomisation (Visit 2) in vital signs at end of treatment
26. Change from screening (Visit 0) in physical examinations (including weight) at end of treatment
27. Change from screening (Visit 0) in ECG at end of treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of the trial

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

Yes

E.8.1.7.1

Other trial design description

There is one single blind phase during the study

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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:

538

F.1.3

Elderly (>=65 years)

Yes

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

548

F.4.2.2

In the whole clinical trial

548

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)

After the end of the trial, the patients will be treated according to local standard practice. No further post-trial therapy will be offered by the sponsor.

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

2018-10-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-03-30

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