Multiple Sclerosis (MS)Phase 3RELEASE MSS3NCT04203498
Safety and Effectiveness of Nabiximols Oromucosal Spray as Add-on Therapy in Participants With Spasticity Due to Multiple Sclerosis
A Phase 3 study testing Nabiximols in people with Multiple Sclerosis (MS), run by Jazz Pharmaceuticals at 37 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis (MS)
- What is being tested?
- Nabiximols
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 139 participants
- Where
- 37 sitesin 5 countries
- Study dates
- 1 Oct 2020to 28 Feb 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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).
Trial locations and contacts
37 sites in 5 countries.
37 sites in 5 countries
United States15 sites
Shepherd Center
Atlanta, Georgia, 30309
American Health Network of Indiana
Avon, Indiana, 46123
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 35233
Neurology Clinic - Cordova
Cordova, Tennessee, 38018
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Cincinnati (UC) Health
Dayton, Ohio, 45417
Hope Neurology
Knoxville, Tennessee, 37922
Ochsner Medical Center
New Orleans, Louisiana, 70121
Consultants in Neurology - Northbrook
Northbrook, Illinois, 60062
Neurostudies - Port Charlotte
Port Charlotte, Florida, 33952
Raleigh Neurology Associates - Raleigh Location
Raleigh, North Carolina, 27607
Central Texas Neurology Consultants
Round Rock, Texas, 78681
The Multiple Sclerosis Center For Innovations In Care
St Louis, Missouri, 63131
University of South Florida
Tampa, Florida, 33613
Accel Research Sites - Enterprise
Tampa, Florida, 33634
Poland12 sites
Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163
Neuro-Medic Janusz Zbrojkiewicz
Katowice, Silesian Voivodeship, 40-555
RESMEDICA Poradnia Neurologiczna
Kielce, Świętokrzyskie Voivodeship, 25-726
SP ZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Norberta Barlickiego w Łodzi
Lodz, 90-001
Centrum Medyczne Oporów
Lublin, 20-855
Neurologiczny NZOZ Centrum Leczenia SM Ośrodek Badań Klinicznych im. dr n. med. Hanki Hertmanowskiej Witosław Cieślak
Plewiska, 62-064
Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
Poznan, Greater Poland Voivodeship, 61-853
Centrum Medyczne Neuroprotect
Warsaw, Masovian Voivodeship, 01-684
Centrum Medyczne Pratia - Warszawa
Warsaw, Masovian Voivodeship, 01-868
Wromedica Centrum Zdrowia
Wroclaw, Lower Silesian Voivodeship, 51-685
Wromedica Centrum Zdrowia
Wroclaw, 51-685
Wielospecjalistyczne Centrum Medyczne Ibismed
Zabrze, Silesian Voivodeship, 41-800
Czechia5 sites
Poliklinika Choceň
Choceň, Pardubice, 565 01
Neurologie Taláb Radomír Doc. MUDr., CSc
Hradec Králové, 500 03
Nemocnice Jihlava
Jihlava, 586 01
Fakultní Nemocnice Královské Vinohrady
Prague, 100 34
Krajská Zdravotní - Nemocnice Teplice
Teplice, 415 29
Romania4 sites
Centrul Medical Clubul Sanatatii
Campulung Muscel, 115100
Spitalul Municipal Caracal
Caracal, 235200
Spitalul Clinic Cai Ferate Constanta
Constanța, 900123
Spitalul Municipal Sf. Dr. Cosma si Damian Radauti
Radauti, 725400
About this study
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
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).
Read the 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.
- Conditions
- Multiple Sclerosis (MS)
- Being tested
- Nabiximols, Placebo
- Keywords
- Spasticity
- Medical subject headings
- Multiple Sclerosis, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NabiximolsDrug
Also called GW-1000-02, Sativex
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nabiximols | Experimental | Not described Receives: Drug: Nabiximols |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period
The change in the average daily spasm count was assessed compared to the baseline period.
Measured: Baseline to Week 12
Secondary outcomes (14)
Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score
The MSSS-88 is a self-reported measure of the impact of spasticity (muscle stiffness and spasms) in MS. This 88-item scale captures the patient experience and impact of spasticity, including muscle stiffness, pain and discomfort, muscle spasms, effect on daily activities, ability to walk, body movement, patient feelings, and social functioning. Responses to individual questions can range from "1 - not at all bothered" to "4 - extremely bothered", ranging from 88 to 352 total score. Scores are summed and higher scores indicate poor clinical outcome. Least square means are being reported, with greater negative values indicating better outcome.
Measured: Week 8 and Week 12
Number of Patients Reporting Any Treatment-emergent Adverse Events
A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product.
Measured: From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks
Change From Baseline in Clinical Laboratory Test Values
Measured: Baseline up to Week 12
Change From Baseline in Erythrocytes
Measured: Baseline up to Week 12
Change From Baseline in Hemoglobin
Measured: Baseline up to Week 12
Change From Baseline in Hematocrit Ratio
The hematocrit ratio measures the volume of red blood cells compared to the total blood volume.
Measured: Baseline up to Week 12
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
Measured: Baseline up to Week 12
Change From Baseline in Blood Pressure
Measured: Baseline up to Week 12
Change From Baseline in Heart Rate
Measured: Baseline up to Week 12
Change From Baseline in Electrocardiogram Parameters
Measured: Baseline up to Week 12
Change From Baseline in Electrocardiogram Pulse Rate
Measured: Baseline up to Week 12
Change From Baseline in Weight
Measured: Baseline up to Week 12
Change in Body Mass Index
Measured: Baseline up to Week 12
Number of Patients With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a short questionnaire that is used to assess suicidal ideation (5 questions) and behavior (5 questions) since last patient visit. The questionnaire is completed by participants answering yes or no to each question.
Measured: Screening up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2019
- Study start1 Oct 2020
- Primary completion10 Feb 2023
- Study completion28 Feb 2023
Why it stopped: This study was terminated based on a business decision by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Sclerosis (MS)Studies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04203498
- Sponsor's protocol ID
- GWSP18023
- Other IDs
- 2019-002623-14, 2019
- Acronym
- RELEASE MSS3
- Status last verified
- Apr 2024
- First submitted
- 17 Dec 2019
- Last updated
- 8 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04203498
- Acronym / sponsor ID
- RELEASE MSS3 / GWSP18023
- Conditions
- Multiple Sclerosis (MS)
- Keywords
- Spasticity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated based on a business decision by the Sponsor.
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 10 Feb 2023 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 18 Dec 2019 (actual)
- Results
- Posted 8 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nabiximols | Experimental | Drug: Nabiximols |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NabiximolsAlso: GW-1000-02, SativexNabiximols 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. | Drug | Nabiximols |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period
Time frame: Baseline to Week 12
The change in the average daily spasm count was assessed compared to the baseline period.
14 secondary outcomes
Change in Multiple Sclerosis Spasticity Scale (MSSS-88) Total Score
Time frame: Week 8 and Week 12
Number of Patients Reporting Any Treatment-emergent Adverse Events
Time frame: From date of first dose of IMP up to 30 days after last dose, up to approximately 16 weeks
Change From Baseline in Clinical Laboratory Test Values
Time frame: Baseline up to Week 12
Change From Baseline in Erythrocytes
Time frame: Baseline up to Week 12
Change From Baseline in Hemoglobin
Time frame: Baseline up to Week 12
Change From Baseline in Hematocrit Ratio
Time frame: Baseline up to Week 12
Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin
Time frame: Baseline up to Week 12
Change From Baseline in Blood Pressure
Time frame: Baseline up to Week 12
Change From Baseline in Heart Rate
Time frame: Baseline up to Week 12
Change From Baseline in Electrocardiogram Parameters
Time frame: Baseline up to Week 12
Change From Baseline in Electrocardiogram Pulse Rate
Time frame: Baseline up to Week 12
Change From Baseline in Weight
Time frame: Baseline up to Week 12
Change in Body Mass Index
Time frame: Baseline up to Week 12
Number of Patients With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Screening up to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
37 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nabiximols in people with Multiple Sclerosis (MS), run by Jazz Pharmaceuticals at 37 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, Poland, Czechia, Romania, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Average Daily Spasm Count From Baseline to Week 12 By 4-Week Period During the 12-Week Randomized Period (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.