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Spasticity With Multiple SclerosisPhase 3RELEASE MSS5NCT04984278

Evaluation of the Effect of Nabiximols Oromucosal Spray on Clinical Measures of Spasticity in Participants With Multiple Sclerosis

A Phase 3 study testing Nabiximols in people with Spasticity With Multiple Sclerosis, run by Jazz Pharmaceuticals at 30 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will be conducted 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 participants with multiple sclerosis (MS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Spasticity With Multiple Sclerosis
What is being tested?
Nabiximols
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
56 participants
Where
30 sitesin 5 countries
Study dates
16 Aug 2021to 11 Nov 2022
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

  • Screening (Visit 1)
  • 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 multiple sclerosis (MS), by revised 2017 McDonald criteria, for at least 12 months prior to Visit 1 (Screening) and is expected to remain stable for the duration of the trial
  • Has an Modified Ashworth Scale (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 (Screening)
  • If currently receiving approved anti-spasticity therapy, it must be with a stable dosing regimen for at least 30 days prior to Visit 1 (Screening). The participant 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.
Show all 10Show fewer
  • 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 (Screening) 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 (Screening) and is expected to remain stable for the duration of the trial.
  • Additional Inclusion Criteria at Randomization (Visit 2)
  • Completed at least 5 of 7 days of their electronic diary reporting during the 7 days immediately preceding Visit 2 (Day 1)

Who cannot join

  • Has taken nabiximols, cannabis, or a cannabis-derived product for medicinal or recreational purposes in the 30 days prior to Visit 1 (Screening) 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 (Screening)
  • Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the participant'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 participant's spasticity
  • Has had a relapse of MS within the 60 days prior to Visit 1 (Screening)
  • Currently using botulinum toxin injection for the relief of spasticity (within 6 months of Visit 1 [Screening]) or is unwilling to abstain for the duration of the trial
Show all 24Show fewer
  • Currently taking antipsychotic medication
  • Currently taking benzodiazepines unless doses and dosing regimen have been stable for at least 30 days prior to Visit 1 (Screening)
  • 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 investigational medicinal product (IMP)
  • 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. Participants 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 [Screening] or Visit 2 [Day 1]), lactating, or planning pregnancy during the course of the trial or within 3 months thereafter.
  • Has received an IMP within the 30 days prior to Visit 1 (Screening)
  • Has any other clinically significant disease or disorder (including seizure disorder) that, in the opinion of the investigator, may put the participant, other participants, or site staff at risk because of participation in the trial, influence the interpretation of trial results, or may affect the participant's ability to take part in the trial
  • Has any abnormalities identified following a physical examination, clinical laboratory, serology, or other applicable screening procedures that, in the opinion of the investigator, would jeopardize the safety of the participant or the conduct of the study if he or she took part in the trial
  • Has any history of suicidal behavior in the 5 years prior to Visit 1 (Screening) or a score of 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the month prior to Visit 1 (Screening)
  • Has any known or suspected history of alcohol or substance abuse (including opiate abuse) or dependence within 1 year prior to Visit 1 (Screening)
  • Currently using an illicit drug or current nonprescribed use of any prescription drug
  • Has a history of psychiatric or neurologic disorder that, in the opinion of the investigator, may interfere with trial participation, data interpretation, or conduct of trial procedures
  • Has a history of severe psychiatric disorder that may be exacerbated by the use of a cannabinoid-containing product
  • Has any planned clinical interventions or intends to change any or all medications that may have an effect on spasticity or MS during the trial
  • Currently taking drugs that are solely metabolized by UGT1A9 and UGT2B7
  • Currently taking strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's Wort)

Trial locations and contacts

30 sites in 5 countries.

30 sites in 5 countries

Poland12 sites

  • Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163

  • MA-LEK A.M. Maciejowscy S.C. Centrum Terapii SM

    Katowice, Silesian Voivodeship, 40-571

  • DENDRYT Centrum Medyczne

    Katowice, Silesian Voivodeship, 40-684

  • Neuro-Medic Janusz Zbrojkiewicz

    Katowice, Silesian Voivodeship, 40-686

  • RESMEDICA Poradnia Neurologiczna

    Kielce, Świętokrzyskie Voivodeship, 25-726

  • Małopolskie Centrum Kliniczne

    Krakow, Lesser Poland Voivodeship, 30-149

  • Indywidualna Praktyka Lekarska Dr Hab Konrad Rejdak

    Lublin, Lublin Voivodeship, 20-016

  • Instytut Zdrowia dr Boczarska-Jedynak

    Oświęcim, Lesser Poland Voivodeship, 32-600

  • Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD

    Poznan, Greater Poland Voivodeship, 61-853

  • Centrum Medyczne Pratia - Warszawa

    Warsaw, Masovian Voivodeship, 01-868

  • Szpital Wolski im dr. Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej

    Warsaw, Masovian Voivodeship

  • Wielospecjalistyczne Centrum Medyczne Ibismed

    Zabrze, Silesian Voivodeship, 41-800

Other trials in Poland

United States6 sites

  • Consultants in Neurology - Northbrook

    Chicago, Illinois, 60062

  • Neurology Clinic-Cordova

    Cordova, Tennessee, 38018

  • Mountain View Clinical Research

    Denver, Colorado, 80209

  • Premier Neurology Research, PC

    Greer, South Carolina, 29650

  • Collier Neurologic Specialists

    Naples, Florida, 34105

  • University of South Florida

    Tampa, Florida, 33613

Other trials in United States

United Kingdom5 sites

  • NHS Highland

    Inverness, Scotland, IV2 3UJ

  • Panthera Biopartners - North London

    North London, England, EN1 1LJ

  • ReCognition Health - Plymouth

    Plymouth, England, PL6 8BT

  • Panthera Biopartners - Preston

    Preston, England, PR2 9QB

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, England, S10 2JF

Other trials in United Kingdom

Spain4 sites

  • Institut Hospital del Mar d'Investigacions Mèdiques

    Barcelona, 8003

  • Hospital Universitario de Getafe

    Getafe, Madrid, 289005

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Vithas Nisa Sevilla

    Seville, 41009

Other trials in Spain

Czechia3 sites

  • NeuropsychiatrieHK

    Choceň, 565 01

  • NeuropsychiatrieHK

    Hradec Králové, 503 41

  • Krajská Zdravotní - Nemocnice Teplice

    Teplice, 415 29

Other trials in Czechia

About this study

Official title: 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

This study will be conducted 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 participants with multiple sclerosis (MS). LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS)-transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body.

Read the detailed description

Each period of this multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial includes a 7-day Baseline period, a 3-week treatment period (comprising a 2-week titration phase and a 1-week maintenance phase).

Eligible participants will enter the 7-day baseline period of each treatment period. During baseline, participants will maintain their optimized oral MS antispasticity medication regimen and record their 11-point Numerical Rating Scale (NRS) spasticity score and spasm count using an electronic daily diary. On Day 1, eligible participants will be randomized to 1 of 2 treatment sequences, each composed of 2 treatment periods, with administration of multiple doses of 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 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.

Lower limb muscle tone, health-related quality of life, safety, tolerability, and pharmacokinetics will be evaluated during the treatment period.

Participants who complete the trial will participate for a total of approximately 11 weeks (77 days), including the 7-day baseline period.

Being tested
Nabiximols, Placebo
Keywords
multiple sclerosis, MS, spasticity, velocity-dependent muscle tone, nabiximols
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

    oromucosal spray

  • PlaceboDrug

    oromucosal spray

Study groups in NCT04984278
Study groupRoleWhat they receive
NabiximolsExperimentalNabiximols 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. Study dependent: Each spray delivers 100 microliters (μL) of nabiximols. A pre-determined number of sprays, but no less than 4 sprays, of nabiximols will be self-administered by participants as an oromucosal spray, under supervision of trial staff during 2 study visits to the trial site after they temporarily discontinued treatment with prescribed nabiximols (Sativex) as part of their regular medication.
Receives: Drug: Nabiximols
PlaceboPlacebo comparatorPlacebo to match nabiximols is 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 delivers 100 μL containing no active ingredients.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Lower Limb Muscle Tone-6 (LLMT-6)

    LLMT-6 is defined as the average of the 6 individual Modified Ashworth Scale (MAS) transformed scores of knee flexors, knee extensors, and plantar flexors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-6 score is being reported. Negative values indicate an improvement in muscle tone.

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

Secondary outcomes (13)

  1. Change From Baseline in Lower Limb Muscle Tone-4 (LLMT-4)

    LLMT-4 is defined as the average of the 4 individual MAS transformed scores of knee flexors and knee extensors on both sides of the body. Transformed MAS ranges from 0 (no increase in muscle tone) to 5 (affected part rigid in flexion or extension). The combined (treatment period 1 and treatment period 2) least square mean change from baseline in LLMT-4 score is being reported. Negative values indicate an improvement in muscle tone.

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  2. Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)

    A TEAE is an adverse event that started, or worsened in severity or seriousness, following the first dose of the investigational medicinal product.

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  3. Change From Baseline in Blood Pressure

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  4. Change From Baseline in Heart Rate

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  5. Change From Baseline in Clinical Laboratory Test Values

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  6. Change From Baseline in Erythrocytes

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  7. Change From Baseline in Hemoglobin

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  8. Change From Baseline in Hematocrit Ratio

    Hematocrit was measured in whole blood samples. The ratio of packed cells to total volume was assessed. Normal ratio ranges from 0.350-0.470 female and 0.400-0.540 male (normal ranges per our central lab), 0.37 (or 37%) to 0.52 (or 52%) in adults. Lower hematocrit ratios indicate worse clinical outcome.

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  9. Change From Baseline in Erythrocyte Mean Corpuscular Volume

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  10. Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  11. Change From Baseline in Electrocardiogram Parameters

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  12. Change From Baseline in Electrocardiogram Pulse Rate

    Measured: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)

  13. Number of Participants With Suicidal Ideation or Behavior Based on The Columbia Suicide Severity Rating Scale (CSSRS)

    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: Baseline, Day 15, and Day 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2021
  2. Study start16 Aug 2021
  3. Primary completion11 Nov 2022
  4. Study completion11 Nov 2022

Why it stopped: The study was terminated based on a business decision by the Sponsor.

Resources

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
Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04984278
Sponsor's protocol ID
GWSP20105
Other IDs
2020-003271-18
Acronym
RELEASE MSS5
Status last verified
Dec 2024
First submitted
14 Jul 2021
Last updated
11 Dec 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nabiximols in people with Spasticity With Multiple Sclerosis, run by Jazz Pharmaceuticals at 30 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 10 inclusion and 24 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 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Poland, United States, United Kingdom, Spain, Czechia. 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 5 Feb 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 From Baseline in Lower Limb Muscle Tone-6 (LLMT-6) (time frame: Baseline (predose Day 1 of Treatment Period 1) up to Day 51 (end of treatment of Treatment Period 2)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04984278.

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 11 Dec 2024.

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