Clinical Trials Register

Summary
EudraCT Number:	2020-003271-18
Sponsor's Protocol Code Number:	GWSP20105
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-04-07
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

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2020-003271-18

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled, 2-way Crossover Trial to Evaluate the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Patients with Multiple Sclerosis

Dvojitě zaslepené, randomizované, placebem kontrolované, dvouramenné, zkřížené klinické hodnocení hodnotící účinek orálního spreje nabiximols na klinické parametry spasticity u pacientů s roztroušenou sklerózou

A.3.1

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

A trial to test how efficient Nabiximols is for treatment of spacticity in patients with Multiple Sclerosis

A.4.1

Sponsor's protocol code number

GWSP20105

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	GW Pharma Limited
B.1.3.4	Country	United Kingdom
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	GW Pharma Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GW Pharma Limited
B.5.2	Functional name of contact point	Regulatory affairs manager
B.5.3	Address:
B.5.3.1	Street Address	Sovereign House, Vision Park, Chivers Way, Histon
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB24 9BZ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	44 1223 266800
B.5.5	Fax number	44 1223235667
B.5.6	E-mail	gwreg@gwpharm.com

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	Yes
D.2.1.1.1	Trade name	Sativex Oromucosal Spray
D.2.1.1.2	Name of the Marketing Authorisation holder	GW Pharma Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Nabiximols - Sativex
D.3.4	Pharmaceutical form	Oromucosal spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oromucosal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tetrahydrocannabinol Botanical Drug Substance (THC BDS)
D.3.9.1	CAS number	1972-08-3
D.3.9.3	Other descriptive name	DELTA-9-TETRAHYDROCANNABINOL
D.3.9.4	EV Substance Code	SUB27785
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	27
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cannabidiol Botanical Drug Substance (CBD BDS)
D.3.9.1	CAS number	13956-29-1
D.3.9.3	Other descriptive name	CANNABIDIOL
D.3.9.4	EV Substance Code	SUB26600
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	No

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	Oromucosal spray, solution
D.8.4	Route of administration of the placebo	Oromucosal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Symptomatic treatment of spasticity in patients with multiple sclerosis (MS)

E.1.1.1

Medical condition in easily understood language

Treatment of muscle spasm in patients with multiple sclerosis (MS)

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	PT
E.1.2	Classification code	10028335
E.1.2	Term	Muscle spasticity
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
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

To evaluate the effect of multiple doses of nabiximols compared with placebo on a clinical measure of velocity-dependent muscle tone in the lower limbs (Lower Limb Muscle Tone-6; LLMT-6) in patients with MS

E.2.2

Secondary objectives of the trial

• To evaluate the effect of multiple doses of nabiximols compared with placebo on a clinical measure of velocity-dependent muscle tone in the lower limbs (Lower Limb Muscle Tone 4; LLMT-4) in patients with MS
• To evaluate the safety and tolerability of nabiximols after administration of multiple doses
• To evaluate the pharmacokinetic (PK) profile of nabiximols after administration of multiple doses

Exploratory Objectives:
• To evaluate the effect of nabiximols after administration of multiple doses on walking using the Timed 25-Foot Walk (T25FW) test
• To evaluate the effect of nabiximols after administration of multiple doses on the following patient-reported outcomes:
− The 11-point Numerical Rating Scale (NRS) spasticity score
− Daily spasm count
− The MS Spasticity Scale (MSSS-88) total and subdomain scores

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female, aged 18 years or above.
• Willing and able to give informed consent for participation in the trial.
• Willing and able (in the investigator’s opinion) to comply with all trial requirements.
• Has had a diagnosis with any disease subtype of MS, by revised 2017 McDonald criteria, for at least 12 months prior to Visit 1 and is expected to remain stable for the duration of the trial.
• Has an MAS untransformed score of at least 2 in 2 or more of 6 muscle groups (right knee flexors, left knee flexors, right knee extensors, left knee extensors, right plantar flexors, or left plantar flexors) at Visit 1.
• If currently receiving approved anti-spasticity therapy, it must be with a stable dosing regimen for at least 30 days prior to Visit 1. The patient must be willing to maintain the same antispasticity medication and not plan to initiate a new course of physiotherapy for the duration of the trial.
• If currently receiving an approved MS disease-modifying therapy, it must be at a stable dose for at least 3 months prior to Visit 1 and be expected to remain stable for the duration of the trial.
• If currently receiving dalfampridine or fampridine, it must be at a stable dose for at least 3 months prior to Visit 1 and is expected to remain stable for the duration of the trial.
• Willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
• Willing to allow his or her primary care practitioner (if he or she has one) and/or treating neurologist (if he or she has one) to be notified of participation in the trial, if the primary care practitioner/treating neurologist is different from the investigator.
Additional Inclusion Criteria at Randomization (Visit 2)
Patients are eligible for randomization in the trial if, in addition to continuing to meet the Screening (Visit 1) inclusion criteria, they also meet the following criterion prior to Visit 2 (Day 1):
• Completed at least 5 of 7 days of their electronic diary reporting during the 7 days immediately preceding Visit 2 (Day 1).

E.4

Principal exclusion criteria

• Has taken nabiximols, cannabis, or a cannabis-derived product for medicinal or recreational purposes in the 30 days prior to Visit 1 or unable to abstain for the duration of the study.
• Did not tolerate or did not respond adequately to treatment with nabiximols or another cannabis-based medication if exposed at any time before the 30-day period prior to Visit 1.
• Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the patient’s level of spasticity.
• Medical history suggests that relapse/remission is likely to occur during the trial, which, in the opinion of the investigator, is expected to influence the patient’s spasticity.
• Has had a relapse of MS within the 60 days prior to Visit 1.
• Currently using botulinum toxin injection for the relief of spasticity (within 6 months of Visit 1) or is unwilling to abstain for the duration of the trial.
• Currently taking antipsychotic medication.
• Currently taking benzodiazepines unless doses and dosing regimen have been stable for at least 30 days prior to Visit 1.
• Clinically suspected to have a contracture in one of the muscle groups of the lower limbs, preventing assessment with the MAS.
• Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP.
• Has experienced myocardial infarction or clinically significant cardiac dysfunction within the 12 months prior to Visit 1 or has a cardiac disorder that, in the opinion of the investigator, would put the patient at risk of a clinically significant arrhythmia or myocardial infarction.
• Has a diastolic blood pressure of < 50 mmHg or > 105 mmHg or systolic blood pressure < 90 mmHg or > 150 mmHg (when measured in a sitting position at rest for 5 minutes) or a postural drop in the systolic blood pressure of > 20 mmHg at Visit 1 or Visit 2. All measurements will be performed singly and can be repeated once, if any are outside the reference range but not considered clinically significant.
• Has clinically significant impaired renal function at Visit 1, as evidenced by an estimated creatinine clearance lower than 50 mL/min. All measurements will be performed singly and can be repeated once, if any are outside the reference range but not considered clinically significant.
• Has moderately impaired hepatic function at Visit 1, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN). All measurements will be performed singly and can be repeated once, if any are outside the reference range but not considered clinically significant.
• Male and fertile (i.e., after puberty unless permanently sterile by bilateral orchiectomy) unless willing to ensure that he uses male contraception (condom or vasectomy) or remains sexually abstinent during the trial and for 3 months thereafter.
• Female and of childbearing potential (i.e., following menarche and until becoming postmenopausal for ≥ 12 consecutive months unless permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) unless willing to ensure that she uses a highly effective method of birth control (e.g., intrauterine device/hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence) during the trial and for 3 months thereafter. Patients using combined hormonal methods or a progestogen-only pill or injection or implant should use an additional barrier method such as a male condom or diaphragm during the trial and for 3 months thereafter.
• Female and pregnant (positive pregnancy test at Visit 1 or Visit 2), lactating, or planning pregnancy during the course of the trial or within 3 months thereafter.

E.5 End points

E.5.1

Primary end point(s)

Change in Lower Limb Muscle Tone-6 (LLMT-6; defined as the average of the 6 individual MAS transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body) from Day 1 predose to Day 21 and from Day 31 predose to Day 51
The MAS scores are transformed using the following algorithm: MAS untransformed [to MAS transformed] scores; 0[0], 1[1], 1+[2], 2[3], 3[4], and 4[5].

E.5.1.1

Timepoint(s) of evaluation of this end point

From Day 1 predose to Day 21 and from Day 31 predose to Day 51

E.5.2

Secondary end point(s)

Efficacy:
• Change in Lower Limb Muscle Tone-4 (LLMT-4; defined as the average of the 4 individual MAS transformed scores of knee flexors and knee extensors on both sides of the body) from Day 1 predose to Day 21 and from Day 31 predose to Day 51
Safety:
• Frequency of treatment-emergent adverse events (TEAEs)
• Change from baseline to each assessment time point by treatment period for the following:
• Clinical laboratory parameters
• Vital signs
• Physical examination procedures
• 12-lead electrocardiograms (ECGs)
• Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, and at each subsequent time point with reference to the last assessment (since last visit)
Pharmacokinetics:
• Plasma concentrations for Δ9-tetrahydrocannabinol (THC) and its relevant metabolites (11-hydroxy-Δ9-tetrahydrocannabinol and 11-carboxy-Δ9-tetrahydrocannabinol) and cannabidiol (CBD) and its relevant metabolites (7-hydroxy-cannabidiol and 7-carboxy-cannabidiol) at distinct time points during each treatment period (Visits 2, 4, 5, 6, 8, and 9)

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy: from Day 1 predose to Day 21 and from Day 31 predose to Day 51

Safety: Change from baseline to each assessment time point by treatment period; Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, and at each subsequent time point with reference to the last assessment (since last visit)

Pharmacokinetics: at distinct time points during each treatment period (Visits 2, 4, 5, 6, 8, and 9)

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

Yes

E.6.7

Pharmacodynamic

Yes

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

Poland

Spain

Czechia

United Kingdom

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:

169

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

177

F.4.2.2

In the whole clinical trial

190

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)

There will be no post-trial provision of Nabiximols.

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

2021-06-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-07

P. End of Trial
P.	End of Trial Status	Ongoing

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