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BX-1 in Spasticity Due to Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03756974
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Bionorica SE

Tracking Information
First Submitted Date  ICMJE November 20, 2018
First Posted Date  ICMJE November 28, 2018
Last Update Posted Date November 5, 2019
Actual Study Start Date  ICMJE February 18, 2019
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
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 [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
Responder analysis: proportion of patients showing improvement in spasticity of 18% or more in average NRS-S assessment at end of treatment [ Time Frame: 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).
Change History Complete list of historical versions of study NCT03756974 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • 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) [ Time Frame: 16 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Weekly mean of the patient's daily spasticity assessments on the NRS-S during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • Weekly mean of the patient's daily pain assessments on the Numerical Rating Scale for Pain (NRS-P) during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Weekly mean of the patient's daily spasm frequency and severity assessments on the Penn Spasm Frequency Scale (PSFS) during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • Mean change from baseline of spasm frequency and severity assessments on the PSFS at end of treatment (Visit 6) [ Time Frame: 16 weeks ]
  • Mean change from baseline of Timed 25-Foot Walk (T25-FW) at Visit 4 and Visit 6 [ Time Frame: 16 weeks ]
  • Responder analysis: proportion of patients showing improvement in TF25-FW (change from baseline) of 20% or more at Visit 6 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Mean change from baseline of sleep quality measured with the Numerical Rating Scale for Sleep Quality (NRS-SQ) at Visit 3 - Visit 6 [ Time Frame: 12 weeks ]
  • Mean change from baseline of fatigue measured with the Numerical Rating Scale for Fatigue (NRS-F) at Visit 3 - Visit 6 [ Time Frame: 12 weeks ]
  • Overall patients' status measured by Patient´s Global Impression of Change scale (PGIC) at Visit 5 and Visit 6 [ Time Frame: 16 weeks ]
  • Overall patients' status measured by Clinical Global Impression - Improvement scale (CGI-I) at Visit 5 and Visit 6 [ Time Frame: 16 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
  • 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) [ Time Frame: 16 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Weekly mean of the patient's daily spasticity assessments on the NRS-S during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • Weekly mean of the patient's daily pain assessments on the NRS-P during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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) [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Weekly mean of the patient's daily spasm frequency and severity assessments on the PSFS during Visit 0 - Visit 6 [ Time Frame: 21 weeks ]
  • Mean change from baseline of spasm frequency and severity assessments on the PSFS at end of treatment (Visit 6) [ Time Frame: 16 weeks ]
  • Mean change from baseline of Timed 25-Foot Walk (T25-FW) at Visit 4 and Visit 6 [ Time Frame: 16 weeks ]
  • Responder analysis: proportion of patients showing improvement in TF25-FW (change from baseline) of 20% or more at Visit 6 [ Time Frame: 16 weeks ]
  • 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 [ Time Frame: 16 weeks ]
  • Mean change from baseline of quality of life measured with SF-36 v2 at Visit 6 [ Time Frame: 16 weeks ]
  • Mean change from baseline of sleep quality measured with the NRS-SQ at Visit 3 - Visit 6 [ Time Frame: 12 weeks ]
  • Mean change from baseline of fatigue measured with the NRS-F at Visit 3 - Visit 6 [ Time Frame: 12 weeks ]
  • Overall patients' status measured by Patient´s Global Impression of Change scale (PGIC) at Visit 5 and Visit 6 [ Time Frame: 16 weeks ]
  • Overall patients' status measured by Clinical Global Impression - Improvement scale (CGI-I) at Visit 5 and Visit 6 [ Time Frame: 16 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BX-1 in Spasticity Due to Multiple Sclerosis
Official Title  ICMJE 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)
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Spasticity Due to Multiple Sclerosis
Intervention  ICMJE
  • Drug: BX-1
    BX-1 (dronabinol), oral solution. All patients enrolled establish their individually tolerable dose by dose Titration.
  • Drug: Placebo
    Placebo of BX-1, oral solution
Study Arms  ICMJE
  • Experimental: BX-1 (dronabinol)
    BX-1
    Intervention: Drug: BX-1
  • Placebo Comparator: Placebo
    Placebo of BX-1
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 27, 2018)
384
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    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 efficient and utilizes 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.

    These are combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner (provided that partner is the sole sexual partner of the female patient and that the vasectomised partner has received medical assessment of the surgical success), and true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not highly effective methods of 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

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. Significant impaired renal function (creatinine clearance < 50 mL/min)
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sabine Mitzenheim +499181231 ext 7035 drospas-1@bionorica.de
Contact: Luitgard Spitznagel-Schminke +499181231 ext 90 drospas-1@bionorica.de
Listed Location Countries  ICMJE Czechia,   Germany,   Hungary,   Poland,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03756974
Other Study ID Numbers  ICMJE DroSpas-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bionorica SE
Study Sponsor  ICMJE Bionorica SE
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christine Neubauer Bionorica SE
PRS Account Bionorica SE
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP