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

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2018-000001-23-ES
• Date of registration: 23/08/2018
• Prospective Registration: Yes
• Primary sponsor: Bionorica SE
• Public title: 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
• Scientific title: 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 - BX-1 in spasticity due to MS
• Date of first enrolment: 06/11/2018
• Target sample size: 548
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000001-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Patients are single-blind during the titration phase; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Hungary, Spain

Contacts

• Name: Clinical Operations R&D
• Affiliation: Bionorica SE

• Name: Clinical Operations R&D
• Affiliation: Bionorica SE

Key inclusion & exclusion criteria

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
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 which must include at least baclofen and/or oral tizanidine at both treatment attempts which can be combined with other anti-spasticity drugs. 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.
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
Are the trial subjects under 18? no
Number of subjects for this age range:
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 10

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 screening 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 according to medical history
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 (creatinine clearance < 50 mL/min)
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Symptomatic relief of spasticity in patients with multiple sclerosis
MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Dronabinol
Product Code: BX-1
Pharmaceutical Form: Oral solution
INN or Proposed INN: Dronabinol
CAS Number: 1972-08-3
Current Sponsor code: BX-1
Other descriptive name: Dronabinol
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

Timepoint(s) of evaluation of this end point: At the end of the trial

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).

Secondary Objective: 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

Secondary Outcome(s)

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 severity 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

Timepoint(s) of evaluation of this end point: At the end of the trial

Secondary ID(s)

2018-000001-23-HU

DroSpas-1

Source(s) of Monetary Support

Bionorica SE

Ethics review

Status: Approved
Approval date: 11/10/2018
Contact:

Results

• Results available: Yes
• Date Posted: 23/03/2022
• Date Completed: 30/03/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000001-23/results