BX-1 in Spasticity Due to Multiple Sclerosis

• Sponsor: Bionorica SE (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03756974
• Collaborator: (none)
• Enrollment: 397
• Locations: 40
• Arms: 2
• Actual Duration (Months): 25.3
• Patients Per Site: 9.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To investigate the efficacy and safety of orally administered BX-1 compared to placebo in patients with spasticity due to multiple sclerosis not sufficiently controlled by current anti-spasticity medication

Condition or Disease	Intervention/Treatment	Phase
Spasticity Due to Multiple Sclerosis	Drug: BX-1; Drug: Placebo	Phase 3

Detailed Description

The aim of the present phase III clinical trial is to demonstrate superiority of BX-1, an oral solution containing dronabinol, over placebo in patients with spasticity due to MS not sufficiently controlled by their current anti-spasticity medication.

The trial is designed to show that BX-1 is able to reduce spasticity in MS patients not showing sufficient response to their current anti-spasticity treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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 (MS)
• Actual Study Start Date: Feb 18, 2019
• Actual Primary Completion Date: Mar 30, 2021
• Actual Study Completion Date: Mar 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BX-1 (dronabinol) BX-1	Drug: BX-1; BX-1 (dronabinol), oral solution. All patients enrolled establish their individually tolerable dose by dose Titration.
Placebo Comparator: Placebo Placebo of BX-1	Drug: Placebo; Placebo of BX-1, oral solution

Outcome Measures

Primary Outcome Measures

1. Responder analysis: proportion of patients showing improvement in spasticity of 18% or more in average Numerical Rating Scale for Spasticity (NRS-S) assessment at end of treatment [16 weeks]

   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 Outcome Measures

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) [16 weeks]

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) [16 weeks]

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 [16 weeks]

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 [16 weeks]

5. Weekly mean of the patient's daily spasticity assessments on the NRS-S during Visit 0 - Visit 6 [21 weeks]

6. Weekly mean of the patient's daily pain assessments on the Numerical Rating Scale for Pain (NRS-P) during Visit 0 - Visit 6 [21 weeks]

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) [16 weeks]

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) [16 weeks]

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 [16 weeks]

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 [16 weeks]

11. Weekly mean of the patient's daily spasm frequency and severity assessments on the Penn Spasm Frequency Scale (PSFS) during Visit 0 - Visit 6 [21 weeks]

12. Mean change from baseline of spasm frequency and severity assessments on the PSFS at end of treatment (Visit 6) [16 weeks]

13. Mean change from baseline of Timed 25-Foot Walk (T25-FW) at Visit 4 and Visit 6 [16 weeks]

14. Responder analysis: proportion of patients showing improvement in TF25-FW (change from baseline) of 20% or more at Visit 6 [16 weeks]

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 weeks]

16. Mean change from baseline of quality of life measured with Short-Form Health Survey of the Medical Outcomes Study Version 2 (SF-36 v2) at Visit 6 [16 weeks]

17. Mean change from baseline of sleep quality measured with the Numerical Rating Scale for Sleep Quality (NRS-SQ) at Visit 3 - Visit 6 [12 weeks]

18. Mean change from baseline of fatigue measured with the Numerical Rating Scale for Fatigue (NRS-F) at Visit 3 - Visit 6 [12 weeks]

19. Overall patients' status measured by Patient´s Global Impression of Change scale (PGIC) at Visit 5 and Visit 6 [16 weeks]

20. Overall patients' status measured by Clinical Global Impression - Improvement scale (CGI-I) at Visit 5 and Visit 6 [16 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

1. 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

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 screening in an unstable dosage regimen

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 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 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. Significant 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Choceň		Czechia	56501
2	Investigative Site	Havířov		Czechia	73601
3	Investigative Site	Hradec Králové		Czechia	50003
4	Investigative site	Hradec Králové		Czechia	50341
5	Investigative Site	Olomouc		Czechia	77520
6	Investigative Site	Plzen		Czechia	31200
7	Investigative Site	Praha		Czechia	10034
8	Investigative Site	Praha		Czechia	12808
9	Investigative Site	Praha		Czechia	14059
10	Investigative Site	Praha		Czechia	18600
11	Investigative Site	Teplice		Czechia	41529
12	Investigative Site	Freiburg		Germany	79106
13	Investigative Site	Ulm		Germany	89073
14	Investigative Site	Budapest		Hungary	1024
15	Investigative Site	Budapest		Hungary	1116
16	Investigative Site	Budapest		Hungary	1145
17	Investigative Site	Debrecen		Hungary	4031
18	Investigative Site	Győr		Hungary	9024
19	Investigative Site	Miskolc		Hungary	3526
20	Investigative Site	Szeged		Hungary	6725
21	Investigative Site	Szolnok		Hungary	5000
22	Investigative Site	Tatabánya		Hungary	2800
23	Investigative Site	Bydgoszcz		Poland	85-065
24	Investigative Site	Częstochowa		Poland	42-280
25	Investigative Site	Katowice		Poland	40-555
26	Investigative Site	Katowice		Poland	40-588
27	Investigative Site	Katowice		Poland	40-611
28	Investigative Site	Katowice		Poland	40-650
29	Investigative Site	Kraków		Poland	30-539
30	Investigative Site	Plewiska		Poland	62-064
31	Investigative Site	Poznań		Poland	61-853
32	Investigative Site	Warszawa		Poland	00-874
33	Investigative Site	Warszawa		Poland	01-684
34	Investigative Site	Barcelona		Spain	08003
35	Investigative Site	Barcelona		Spain	08025
36	Investigative Site	Hospitalet de Llobregat		Spain	08907
37	Investigative Site	Madrid		Spain	28034
38	Investigative Site	Málaga		Spain	29010
39	Investigative Site	Salt		Spain	17190
40	Investigative Site	Valencia		Spain	46026

Sponsors and Collaborators

• Bionorica SE

Investigators

• Study Director: Luitgard Spitznagel-Schminke, Bionorica SE

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bionorica SE
• ClinicalTrials.gov Identifier: NCT03756974
• Other Study ID Numbers: DroSpas-1
• First Posted: Nov 28, 2018
• Last Update Posted: May 5, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bionorica SE: cannabinoid; dronabinol
• Additional relevant MeSH terms: Muscle Spasticity; Multiple Sclerosis; Sclerosis

Study Results

No Results Posted as of May 5, 2021