The purpose of this study is to examine the safety and efficacy of VSN16R and the performance in treating spasticity (tightness, stiffness or "pull" of muscles) in patients with Multiple Sclerosis (MS).

• Register: EUCTR
• Last refreshed on: 23 May 2016
• Main ID: EUCTR2014-004412-11-GB
• Date of registration: 19/11/2014
• Prospective Registration: Yes
• Primary sponsor: Canbex Therapeutics Ltd
• Public title: The purpose of this study is to examine the safety and efficacy of VSN16R and the performance in treating spasticity (tightness, stiffness or "pull" of muscles) in patients with Multiple Sclerosis (MS).
• Scientific title: A Phase II Proof of Concept (PoC), Double-Blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of VSN16R for the Treatment of Spasticity in Subjects with Multiple Sclerosis
• Date of first enrolment: 16/01/2015
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004412-11
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Sponsor Representative
• Affiliation: Canbex Therapeutics Ltd

• Name: Sponsor Representative
• Affiliation: Canbex Therapeutics Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
•Be between 18 and 70 years of age, inclusive and having given written informed consent.
•Have a confirmed diagnosis of MS: either, relapsing remitting MS (RRMS), secondary progressive MS (SPMS) or primary progressive MS (PPMS) as per McDonald’s 2010 revised criteria (Polman, 2011).
•Have an Expanded Disability Status Scale (EDSS) = than 6.5 at screening.
•Spasticity due to MS of at least 3 months duration, which is not wholly relieved with current anti-spasticity therapy, and which is expected to remain stable for the duration of the study.
•A minimum score = 4 in the NRS for spasticity as rated by the subject at screening.
•A minimum mean score of =2 on the Ashworth spasticity scale in at least 2 lower extremity muscle groups and a total mASH score of, at least, 4 in the lower extremity muscles tested at screening.
•Normal renal function (estimated CrCl > 60ml/min). Normal hepatic function.
•Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods (including barrier methods, intrauterine device [IUD], and oral contraceptives) for the duration of the study. Women who are of child-bearing potential must continue to use contraception for at least 1 month after their last dose of study medication.
•Men must use barrier contraception for the duration of the study and continue to use it for at least 1 month after their last dose of study medication.
•Willing and able to perform all procedures related to the clinical trial and to provide informed consent.

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 138
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
•Acute MS relapse requiring treatment with steroids within 30 days of screening.
•Initiation or discontinuation of MS disease modifying treatment (DMT) within 30 days of screening.
•Receiving medications that would potentially interfere with the actions of the study medication or outcome variables, including antispastic medications like baclofen, tizanidine, botulinum toxin, cannabinoids, benzodiazepines, gabapentin, pregabalin, smoked cannabis etc.
•Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the subject's level of spasticity.
•Changes in chronic oral medications within 4 weeks of baseline and during study
•Significant abnormalities in screening lab parameters (e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin > 2 ×upper limit of normal [ULN]; creatinine > 2mg/dl; white blood cell [WBC] < 2,300; platelets < 80,000).
•Previous history of dementia, unstable psychiatric disease, or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurological, or cerebral disease.
•Women who are pregnant or breastfeeding.
•History of substance abuse within the past 12 months.
•Participation in another clinical trial within 30 days of V1.
•Subjects who are uncooperative or unwilling to sign consent form.


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

Health Condition(s) or Problem(s) studied

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

Multiple Sclerosis
MedDRA version: 19.0 Level: LLT Classification code 10041416 Term: Spasticity System Organ Class: 100000004852

Intervention(s)

Product Name: VSN16R 100mg
Product Code: VSN16R
Pharmaceutical Form: Capsule
INN or Proposed INN: VSN16R
Other descriptive name: (R) 3-(5-Dimethylcarbamoyl-pent-1-enyl)-N-(2-hydroxy-1- methylethyl) benzamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Efficacy analysis by:
Numerical rating scale(Spasticity)

Timepoint(s) of evaluation of this end point: The primary efficacy analysis for Study Period II of the study will be the modelling of the relationship between dose and change from baseline in NRS for individual participants.

Main Objective: To determine the change in Mean Spasticity in subjects treated with VSN16R as compared to subjects treated with placebo, measured by a NUMERICAL RATING SCALE (NRS) Score, from Baseline before Study Period III (V4) to End of Treatment (V7).

Secondary Objective: •To determine the relationship between the dose of VSN16R and the change in Spasticity, as measured by the NRS Score, from the Baseline before Study Period II (at V2) to the end of Study Period II, in at least the first 50 patients recruited.
•To evaluate change in Mean Spasticity in subjects treated with VSN16R compared to subjects treated with placebo, as measured by the modified ASHWORTH SCALE (mASH) from Baseline before Study Period III (V4) to End of Treatment (V7)
•To compare during Study Period II changes in Spasticity, as measured by the mASH, within each individual subject, from Baseline (time 0) to fixed times intervals (approx. 1, 3, and 6 hours after dosing), for each different dose level (100, 200, 400, and 800mg dose) in at least the first 50 patients recruited.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: *A within subject comparison of NRS and the secondary efficacy outcome variables by dose level versus placebo in Period II of the study using the full analysis set in at least first 50 patients recruited.
*The comparison of the change in the secondary efficacy outcome variables during Sstudy Pperiod III (from V4 to V7) between the VSN16R treatment group and the placebo treatment group within the efficacy evaluable analysis set.
*The comparison of the number of responders at V7 and at V8 between the VSN16R treatment group and the placebo treatment group within the efficacy evaluable analysis set.

Secondary end point(s): Modified Ashworth Scale
Modified Tardieu Scale (mTS)
Timed 10 metre walk (applicable up to EDSS 6.5 subjects)
Spasm count / Pain assessment
CGI-I, PGI-I

Secondary ID(s)

CBX-001

Source(s) of Monetary Support

Canbex Therapeutics Ltd