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

NCT04984278 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: GWSP201052020-003271-18
• Study Type: interventional
• Target: 56
• Locations: 5 countries
• Sites: 30

Brief 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). 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.

Conditions

Spasticity With Multiple Sclerosis

Keywords

multiple sclerosis; MS; spasticity; velocity-dependent muscle tone; nabiximols

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (13)

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

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

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

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

• Change From Baseline in Blood Pressure

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

• Change From Baseline in Heart Rate

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

• Change From Baseline in Clinical Laboratory Test Values

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

Study Arms (2)

Nabiximols

EXPERIMENTAL

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. 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.

Drug: Nabiximols

Placebo

PLACEBO COMPARATOR

Placebo 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.

Drug: Placebo

Interventions

Nabiximols DRUG

oromucosal spray

Also known as: GW-1000-02, Sativex

Nabiximols

Placebo DRUG

oromucosal spray

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• \- Completed at least 5 of 7 days of their electronic diary reporting during the 7 days immediately preceding Visit 2 (Day 1)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (30)

Mountain View Clinical Research

Denver, Colorado, 80209, United States

Location

Collier Neurologic Specialists

Naples, Florida, 34105, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Consultants in Neurology - Northbrook

Chicago, Illinois, 60062, United States

Location

Premier Neurology Research, PC

Greer, South Carolina, 29650, United States

Location

Neurology Clinic-Cordova

Cordova, Tennessee, 38018, United States

Location

NeuropsychiatrieHK

Choceň, 565 01, Czechia

Location

NeuropsychiatrieHK

Hradec Králové, 503 41, Czechia

Location

Krajská Zdravotní - Nemocnice Teplice

Teplice, 415 29, Czechia

Location

Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD

Poznan, Greater Poland Voivodeship, 61-853, Poland

Location

Centrum Medyczne Neuromed - Ośrodek Badań Klinicznych

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163, Poland

Location

Małopolskie Centrum Kliniczne

Krakow, Lesser Poland Voivodeship, 30-149, Poland

Location

Instytut Zdrowia dr Boczarska-Jedynak

Oświęcim, Lesser Poland Voivodeship, 32-600, Poland

Location

Indywidualna Praktyka Lekarska Dr Hab Konrad Rejdak

Lublin, Lublin Voivodeship, 20-016, Poland

Location

Centrum Medyczne Pratia - Warszawa

Warsaw, Masovian Voivodeship, 01-868, Poland

Location

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

Warsaw, Masovian Voivodeship, Poland

Location

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

Katowice, Silesian Voivodeship, 40-571, Poland

Location

DENDRYT Centrum Medyczne

Katowice, Silesian Voivodeship, 40-684, Poland

Location

Neuro-Medic Janusz Zbrojkiewicz

Katowice, Silesian Voivodeship, 40-686, Poland

Location

Wielospecjalistyczne Centrum Medyczne Ibismed

Zabrze, Silesian Voivodeship, 41-800, Poland

Location

RESMEDICA Poradnia Neurologiczna

Kielce, Świętokrzyskie Voivodeship, 25-726, Poland

Location

Hospital Universitario de Getafe

Getafe, Madrid, 289005, Spain

Location

Institut Hospital del Mar d'Investigacions Mèdiques

Barcelona, 8003, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Vithas Nisa Sevilla

Seville, 41009, Spain

Location

Panthera Biopartners - North London

North London, England, EN1 1LJ, United Kingdom

Location

ReCognition Health - Plymouth

Plymouth, England, PL6 8BT, United Kingdom

Location

Panthera Biopartners - Preston

Preston, England, PR2 9QB, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, England, S10 2JF, United Kingdom

Location

NHS Highland

Inverness, Scotland, IV2 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis; Muscle Spasticity

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: July 30, 2021
• Study Start: August 16, 2021
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: December 11, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); PL (12); ES (4); GB (5); CZ (3)