RELEASE MSS3: Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis

Sponsor
Jazz Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04203498
Collaborator
(none)
446
28
2
28
15.9
0.6

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
446 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 1, 2020
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Feb 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nabiximols

Drug: Nabiximols
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.
Other Names:
  • GW-1000-02
  • Sativex
  • Placebo Comparator: Placebo

    Drug: Placebo
    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.

    Outcome Measures

    Primary Outcome Measures

    1. 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) [Baseline, Day 84]

    Secondary Outcome Measures

    1. Change From Baseline in The Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score at Day 85 [Baseline, Day 85]

    2. Number of Participants with Treatment-emergent Adverse Events [Baseline through Day 99]

    3. Number of Participants with Clinically Significant Changes from Baseline in Clinical Laboratory Test Values at Days 29 and 85 [Baseline, Days 29 and 85]

    4. Number of Participants with Clinically Significant Changes from Baseline in Vital Sign Values at Days 15, 29, 57, 85, and 99 [Baseline, Days 15, 29, 57, 85, and 99]

    5. Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Values at Day 85 [Baseline, Day 85]

    6. Number of Participants with Clinically Significant Changes from Baseline in 12-lead Electrocardiogram (ECG) Values at Days 29 and 85 [Baseline, Days 29 and 85]

    7. Mean Columbia-Suicide Severity Rating Scale (C-SSRS) Score at Days 15, 29, 57, and 85 [Days 15, 29, 57, and 85]

    8. Plasma Concentrations for Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Relevant Metabolites at Days 1 (Predose), 15, 29, 57, and 85 [Days 1, 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Criteria at screening:
    1. Participant is male or female aged 18 years or above.

    2. 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.

    3. 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).

    4. 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.

    5. 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:
    1. Participant has any concomitant disease or disorder that has spasticity-like symptoms or that may influence the participant's level of spasticity.

    2. Participant has had a relapse of MS within the 60 days prior to screening (Visit 1).

    3. 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.

    4. 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.

    5. Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP.

    6. 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.

    7. 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.

    8. Participant is female and pregnant, lactating, or planning pregnancy during the course of the trial or within 3 months thereafter.

    9. Participant has received an IMP within the 30 days prior to screening.

    10. Participant has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product.

    11. Participant has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to screening.

    12. Participant is currently taking drugs that are solely metabolized by UGT1A9 and UGT2B7

    13. Participant is currently taking strong currently taking strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Neurostudies - Port Charlotte Port Charlotte Florida United States 33952
    2 University of South Florida Tampa Florida United States 33613
    3 Accel Research Sites - Enterprise Tampa Florida United States 33634
    4 Shepherd Center Atlanta Georgia United States 30309
    5 Consultants in Neurology - Northbrook Northbrook Illinois United States 60062
    6 American Health Network of Indiana Avon Indiana United States 46123
    7 Ochsner Medical Center New Orleans Louisiana United States 70121
    8 The Multiple Sclerosis Center For Innovations In Care Saint Louis Missouri United States 63131
    9 Raleigh Neurology Associates - Raleigh Location Raleigh North Carolina United States 27607
    10 Abington Neurological Associates Abington Pennsylvania United States 19001
    11 Neurology Clinic - Cordova Cordova Tennessee United States 38018
    12 Hope Neurology Knoxville Tennessee United States 37922
    13 Riverside Neurology Specialists - Newport News Newport News Virginia United States 23601
    14 Poliklinika Choceň Choceň Pardubice Czechia 565 01
    15 Neurologie Taláb Radomír Doc. MUDr., CSc Hradec Králové Czechia 500 03
    16 Nemocnice Jihlava Jihlava Czechia 586 01
    17 Fakultní Nemocnice Královské Vinohrady Praha 10 Czechia 100 34
    18 Krajská Zdravotní - Nemocnice Teplice Teplice Czechia 415 29
    19 Wromedica Centrum Zdrowia Wrocław Dolnoslaskie Poland 51-685
    20 Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych Bydgoszcz Kujawsko-Pomorskie Poland 85-163
    21 Centrum Medyczne Neuroprotect Warszawa Mazowieckie Poland 01-684
    22 Centrum Medyczne Pratia - Warszawa Warszawa Mazowieckie Poland 01-868
    23 Neuro-Medic Janusz Zbrojkiewicz Katowice Slaskie Poland 40-555
    24 Wielospecjalistyczne Centrum Medyczne Ibismed Zabrze Slaskie Poland 41-800
    25 RESMEDICA Poradnia Neurologiczna Kielce Swietokrzyskie Poland 25-726
    26 Neurologiczny Niepubliczny ZOZ - Centrum Leczenia SM Ośrodek Badań Klinicznych Plewiska Wielkopolskie Poland 62-064
    27 Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD Poznań Wielkopolskie Poland 61-853
    28 Barts Health NHS Trust London England United Kingdom E1 1BB

    Sponsors and Collaborators

    • Jazz Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jazz Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04203498
    Other Study ID Numbers:
    • GWSP18023
    • 2019-002623-14
    First Posted:
    Dec 18, 2019
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jazz Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 8, 2022