Back to resultsSafety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis (RELEASE MSS3)
Primary Purpose
Multiple Sclerosis (MS)
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Nabiximols
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis (MS) focused on measuring Spasticity
Eligibility Criteria
Inclusion Criteria:
Criteria at screening:
- Participant is male or female aged 18 years or above.
- Participant has had a diagnosis with any disease subtype of multiple sclerosis (MS), by revised 2017 McDonald criteria, for at least 12 months prior to screening and is expected to remain stable for the duration of the trial.
- Participant has had treatment with at least 1 optimized oral antispasticity therapy prior to Visit 1 that must include either oral baclofen or oral tizanidine (monotherapy or combination therapy).
- Participant is currently receiving optimized treatment with at least 1 oral antispasticity medication (baclofen, tizanidine, and/or dantrolene) and has been stable for at least 30 days prior to screening.
- If the participant is currently receiving an approved MS disease-modifying therapy, it must be at a stable dose for at least 3 months prior to screening and is expected to remain stable for the duration of the trial.
Exclusion Criteria:
- Participant has any concomitant disease or disorder that has spasticity-like symptoms or that may influence the participant's level of spasticity.
- Participant has had a relapse of MS within the 60 days prior to screening (Visit 1).
- Participant is currently using or has used cannabis or a cannabinoid-derived product for medicinal or recreational use (within 30 days of screening) and is unwilling to abstain for the duration of the trial.
- Participant is currently using botulinum toxin injection for the relief of spasticity (within 6 months of screening) and is unwilling to abstain for the duration of the trial.
- Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP.
- Participant is male and fertile unless willing to ensure that he uses male contraception or remains sexually abstinent during the trial and for 3 months thereafter.
- Participant is female and of childbearing potential unless willing to ensure that she uses a highly effective method of birth control during the trial and for 3 months thereafter.
- Participant is female and pregnant, lactating, or planning pregnancy during the course of the trial or within 3 months thereafter.
- Participant has received an IMP within the 30 days prior to screening.
- Participant has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product.
- Participant has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to screening.
- Participant is currently taking drugs that are solely metabolized by UGT1A9 and UGT2B7
- Participant is currently taking strong currently taking strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort)
Sites / Locations
- University of Alabama at Birmingham School of Medicine
- Neurostudies - Port Charlotte
- Tallahassee Neurological Clinic
- University of South Florida
- Accel Research Sites - Enterprise
- Shepherd Center
- Consultants in Neurology - Northbrook
- American Health Network of Indiana
- Ochsner Medical Center
- The Multiple Sclerosis Center For Innovations In Care
- Raleigh Neurology Associates - Raleigh Location
- University of Cincinnati (UC) Health
- Abington Neurological Associates
- Neurology Clinic - Cordova
- Hope Neurology
- University of Texas Southwestern Medical Center
- Central Texas Neurology Consultants
- Poliklinika Choceň
- Neurologie Taláb Radomír Doc. MUDr., CSc
- Nemocnice Jihlava
- Fakultní Nemocnice Královské Vinohrady
- Krajská Zdravotní - Nemocnice Teplice
- Wromedica Centrum Zdrowia
- Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych
- Centrum Medyczne Neuroprotect
- Centrum Medyczne Pratia - Warszawa
- Neuro-Medic Janusz Zbrojkiewicz
- Wielospecjalistyczne Centrum Medyczne Ibismed
- RESMEDICA Poradnia Neurologiczna
- Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
- Centrum Medyczne Oporów
- Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak
- Wromedica Centrum Zdrowia
- SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi
- Spitalul Municipal Caracal
- Spitalul Clinic Cai Ferate Constanta
- Centrul Medical Clubul Sanatatii
- Spitalul Municipal Sf. Dr. Cosma si Damian Radauti
- Barts Health NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Nabiximols
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change from Baseline in the Average Daily Spasm Count (from Days 57 to 84 Compared to the Average Daily Spasm Count for the Baseline Period)
Secondary Outcome Measures
Change From Baseline in The Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score at Day 85
Number of Participants with Treatment-emergent Adverse Events
Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Test Values at Days 29 and 85
Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Values at Days 15, 29, 57, 85, and 99
Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Values at Day 85
Number of Participants with Clinically Significant Changes from Baseline in 12-lead Electrocardiogram (ECG) Values at Days 29 and 85
Mean Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Days 15, 29, 57, and 85
Plasma Concentrations for Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Relevant Metabolites at Days 1 (Predose), 15, 29, 57, and 85
Sparse pharmacokinetic (PK) sampling option, blood samples will be taken as follows: Day 1, predose; Days 15, 29, 57, and 85, any time during the visit. Semi-intensive PK sampling option, blood samples will be taken as follows: Day 1, predose. At 1 visit (either Days 15, 29, or 57, 1 sample predose (i.e., prior to administration of investigational medicainal product [IMP] at the investigational site), 1 sample between 2 and 3 hours postdose, 1 sample between 4 and 6 hours postdose, and 1 sample between 6 and 8 hours postdose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04203498
Brief Title
Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis
Acronym
RELEASE MSS3
Official Title
A Double-blind, Randomized, Placebo-controlled, Parallel-group Trial of the Efficacy and Safety of Nabiximols Oromucosal Spray as Add-on Therapy in Patients With Spasticity Due to Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated based on a business decision by the Sponsor.
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
February 10, 2023 (Actual)
Study Completion Date
February 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial is being conducted to demonstrate the efficacy of nabiximols, compared with placebo, when added to standard of care, in the treatment of muscle spasms associated with multiple sclerosis (MS).
Detailed Description
This multicenter, double-blind, placebo-controlled trial includes a 28-day Baseline period, a 12-week treatment period (comprising a 2-week titration phase and a 10-week maintenance phase), and 2-week follow-up period.
Eligible participants will enter the 28-day baseline period. During baseline, participants will maintain their optimized oral MS antispasticity medication regimen and record spasm count using an electronic daily diary. At screening (Day 1), eligible participants will be randomized to either nabiximols or placebo in a 1:1 ratio.
Participants will be advised to titrate the investigational medicinal product (IMP), beginning with 1 spray/day, to an optimized dose or to a maximum of 12 sprays/day over the first 14 days of treatment. Participants may leave a gap between sprays of approximately 15 minutes. Participants should continue at the same dose level achieved at the end of the titration phase ±1 spray divided into a morning dose and an evening dose for the remainder of the treatment period.
Daily spasm count, the participant's symptom experiences, clinician's assessment of spasticity, functional outcomes, health-related quality of life, changes in mood, safety, tolerability, and pharmacokinetics will be evaluated during the treatment period.
Participants who complete the trial will participate for a total of approximately 18 weeks (127 days), including the 28-day baseline period. Participants will have a maximum duration of 85 (±7) days on IMP treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis (MS)
Keywords
Spasticity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
238 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nabiximols
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Nabiximols
Other Intervention Name(s)
GW-1000-02, Sativex
Intervention Description
Nabiximols is a complex botanical medicine formulated from extracts of the cannabis plant that contains the principal cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and also contains minor constituents, including other cannabinoid and non-cannabinoid plant components, such as terpenes, sterols, and triglycerides.Nabiximols will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to match nabiximols will be presented as an oromucosal spray containing the excipients ethanol and propylene glycol (50% v/v) with colorings and flavored with peppermint oil (0.05% v/v). Each spray will deliver 100 microliters (μL) containing no active ingredients. Placebo will be self-administered by participants as an oromucosal spray in the morning and evening, up to a maximum of 12 sprays per day for 12 weeks.
Primary Outcome Measure Information:
Title
Change from Baseline in the Average Daily Spasm Count (from Days 57 to 84 Compared to the Average Daily Spasm Count for the Baseline Period)
Time Frame
Baseline, Day 84
Secondary Outcome Measure Information:
Title
Change From Baseline in The Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score at Day 85
Time Frame
Baseline, Day 85
Title
Number of Participants with Treatment-emergent Adverse Events
Time Frame
Baseline through Day 99
Title
Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Test Values at Days 29 and 85
Time Frame
Baseline, Days 29 and 85
Title
Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Values at Days 15, 29, 57, 85, and 99
Time Frame
Baseline, Days 15, 29, 57, 85, and 99
Title
Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Values at Day 85
Time Frame
Baseline, Day 85
Title
Number of Participants with Clinically Significant Changes from Baseline in 12-lead Electrocardiogram (ECG) Values at Days 29 and 85
Time Frame
Baseline, Days 29 and 85
Title
Mean Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Days 15, 29, 57, and 85
Time Frame
Days 15, 29, 57, and 85
Title
Plasma Concentrations for Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Relevant Metabolites at Days 1 (Predose), 15, 29, 57, and 85
Description
Sparse pharmacokinetic (PK) sampling option, blood samples will be taken as follows: Day 1, predose; Days 15, 29, 57, and 85, any time during the visit. Semi-intensive PK sampling option, blood samples will be taken as follows: Day 1, predose. At 1 visit (either Days 15, 29, or 57, 1 sample predose (i.e., prior to administration of investigational medicainal product [IMP] at the investigational site), 1 sample between 2 and 3 hours postdose, 1 sample between 4 and 6 hours postdose, and 1 sample between 6 and 8 hours postdose
Time Frame
Days 1, 15, 29, 57, and 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Criteria at screening:
Participant is male or female aged 18 years or above.
Participant has had a diagnosis with any disease subtype of multiple sclerosis (MS), by revised 2017 McDonald criteria, for at least 12 months prior to screening and is expected to remain stable for the duration of the trial.
Participant has had treatment with at least 1 optimized oral antispasticity therapy prior to Visit 1 that must include either oral baclofen or oral tizanidine (monotherapy or combination therapy).
Participant is currently receiving optimized treatment with at least 1 oral antispasticity medication (baclofen, tizanidine, and/or dantrolene) and has been stable for at least 30 days prior to screening.
If the participant is currently receiving an approved MS disease-modifying therapy, it must be at a stable dose for at least 3 months prior to screening and is expected to remain stable for the duration of the trial.
Exclusion Criteria:
Participant has any concomitant disease or disorder that has spasticity-like symptoms or that may influence the participant's level of spasticity.
Participant has had a relapse of MS within the 60 days prior to screening (Visit 1).
Participant is currently using or has used cannabis or a cannabinoid-derived product for medicinal or recreational use (within 30 days of screening) and is unwilling to abstain for the duration of the trial.
Participant is currently using botulinum toxin injection for the relief of spasticity (within 6 months of screening) and is unwilling to abstain for the duration of the trial.
Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP.
Participant is male and fertile unless willing to ensure that he uses male contraception or remains sexually abstinent during the trial and for 3 months thereafter.
Participant is female and of childbearing potential unless willing to ensure that she uses a highly effective method of birth control during the trial and for 3 months thereafter.
Participant is female and pregnant, lactating, or planning pregnancy during the course of the trial or within 3 months thereafter.
Participant has received an IMP within the 30 days prior to screening.
Participant has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product.
Participant has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to screening.
Participant is currently taking drugs that are solely metabolized by UGT1A9 and UGT2B7.
Participant is currently taking strong currently taking strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort).
Facility Information:
Facility Name
University of Alabama at Birmingham School of Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Neurostudies - Port Charlotte
City
Port Charlotte
State/Province
Florida
ZIP/Postal Code
33952
Country
United States
Facility Name
Tallahassee Neurological Clinic
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Accel Research Sites - Enterprise
City
Tampa
State/Province
Florida
ZIP/Postal Code
33634
Country
United States
Facility Name
Shepherd Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Consultants in Neurology - Northbrook
City
Northbrook
State/Province
Illinois
ZIP/Postal Code
60062
Country
United States
Facility Name
American Health Network of Indiana
City
Avon
State/Province
Indiana
ZIP/Postal Code
46123
Country
United States
Facility Name
Ochsner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
The Multiple Sclerosis Center For Innovations In Care
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States
Facility Name
Raleigh Neurology Associates - Raleigh Location
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
University of Cincinnati (UC) Health
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Abington Neurological Associates
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Neurology Clinic - Cordova
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
Hope Neurology
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Central Texas Neurology Consultants
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
Facility Name
Poliklinika Choceň
City
Choceň
State/Province
Pardubice
ZIP/Postal Code
565 01
Country
Czechia
Facility Name
Neurologie Taláb Radomír Doc. MUDr., CSc
City
Hradec Králové
ZIP/Postal Code
500 03
Country
Czechia
Facility Name
Nemocnice Jihlava
City
Jihlava
ZIP/Postal Code
586 01
Country
Czechia
Facility Name
Fakultní Nemocnice Královské Vinohrady
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Krajská Zdravotní - Nemocnice Teplice
City
Teplice
ZIP/Postal Code
415 29
Country
Czechia
Facility Name
Wromedica Centrum Zdrowia
City
Wrocław
State/Province
Dolnoslaskie
ZIP/Postal Code
51-685
Country
Poland
Facility Name
Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych
City
Bydgoszcz
State/Province
Kujawsko-Pomorskie
ZIP/Postal Code
85-163
Country
Poland
Facility Name
Centrum Medyczne Neuroprotect
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
01-684
Country
Poland
Facility Name
Centrum Medyczne Pratia - Warszawa
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
01-868
Country
Poland
Facility Name
Neuro-Medic Janusz Zbrojkiewicz
City
Katowice
State/Province
Slaskie
ZIP/Postal Code
40-555
Country
Poland
Facility Name
Wielospecjalistyczne Centrum Medyczne Ibismed
City
Zabrze
State/Province
Slaskie
ZIP/Postal Code
41-800
Country
Poland
Facility Name
RESMEDICA Poradnia Neurologiczna
City
Kielce
State/Province
Swietokrzyskie
ZIP/Postal Code
25-726
Country
Poland
Facility Name
Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
61-853
Country
Poland
Facility Name
Centrum Medyczne Oporów
City
Lublin
ZIP/Postal Code
20-855
Country
Poland
Facility Name
Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak
City
Plewiska
ZIP/Postal Code
62-064
Country
Poland
Facility Name
Wromedica Centrum Zdrowia
City
Wrocław
ZIP/Postal Code
51-685
Country
Poland
Facility Name
SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi
City
Łódź
ZIP/Postal Code
90-001
Country
Poland
Facility Name
Spitalul Municipal Caracal
City
Caracal
ZIP/Postal Code
235200
Country
Romania
Facility Name
Spitalul Clinic Cai Ferate Constanta
City
Constanţa
ZIP/Postal Code
900123
Country
Romania
Facility Name
Centrul Medical Clubul Sanatatii
City
Câmpulung
ZIP/Postal Code
115100
Country
Romania
Facility Name
Spitalul Municipal Sf. Dr. Cosma si Damian Radauti
City
Rădăuți
ZIP/Postal Code
725400
Country
Romania
Facility Name
Barts Health NHS Trust
City
London
State/Province
England
ZIP/Postal Code
E1 1BB
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis
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