A Phase IIb Study of Nabiximols for Spasticity Due to Neuromyelitis Optica Spectrum Disorders

NCT05974293 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2023P002959
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety and efficacy of nabiximols, a cannabinoid spray, for the treatment of moderate to severe spasticity in adult patients with AQP4-IgG positive and antibody-negative NMOSD. The main question it aims to answer is whether treatment with nabiximols improves patient-reported spasticity ratings compared to treatment with a placebo. This trial will also answer whether nabiximols impact pain, spasm frequency, mood, walking ability, and sleep. Participants will be mailed the treatments and placebo treatments, and will be asked to complete study visits and questionnaires remotely. There is also an optional sub-study that involves in-person visits with ultrasound imaging and in-person neurologic exams.

Conditions

NMO Spectrum Disorder; Spasticity, Muscle

Keywords

Neuromyelitis Optica Spectrum Disorders; Nabiximols; Cannabinoid; Sativex

Outcome Measures

Primary Outcomes (1)

• Change in mean Numeric Rating Scale - Spasticity (NRS-S) scores from pre-treatment to post-treatment

  Numeric Rating Scale - Spasticity (NRS-S) score is a 0-10 point, patient-reported scale indicating spasticity severity.

  Baseline; Up to week 18

Secondary Outcomes (17)

• Proportion of participants with NRS-S response corresponding to a minimal clinically important difference (MCID) (>18% difference) from pre-treatment to post-treatment

  Baseline; Up to week 18

• Proportion of participants with NRS-S response corresponding to a clinically important difference (CID) (>30% difference) from pre-treatment to post-treatment

  Baseline; Up to week 18

• Change in Penn Spasm Frequency Scale (PSFS) score from pre-treatment to post-treatment

  Baseline; Up to week 18

• Change in mean PROMIS NRS v1.0 - Pain Intensity 3a scores from pre-treatment to post-treatment

  Baseline; Up to week 18

• Change in mean PROMIS SF v1.1 - Pain Interference 8a scores from pre-treatment to post-treatment

  Baseline; Up to week 18

Other Outcomes (7)

• Change in mean Patient Health Questionnaire-8 (PHQ-8) scores from pre-treatment to post-treatment

  Screening; Up to week 20

• Change in mean PROMIS SF v1.0 - Anxiety 4a scores from pre-treatment to post-treatment

  Screening; Up to week 20

• Change in mean Floodlight-Pinching Test (PT) scores from pre-treatment to post-treatment

  Screening; Up to week 18

Study Arms (2)

Nabiximols, then Placebo

EXPERIMENTAL

During Period 1, participants receive daily nabiximols spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the matched placebo spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.

Drug: Nabiximols; Drug: Placebo

Placebo, then Nabiximols

EXPERIMENTAL

During Period 1, participants receive daily matched placebo spray, delivered by a pump action oromucosal spray. The first 2 weeks of Period 1 are the titration period with participants following pre-specified uptitration schedule, until they reach their individualized optimum daily dosage, with a maximum of 12 daily sprays. Following these 2 weeks, they continue the optimum dose for 4 weeks. Then, they undergo a 2-week washout period, and then, enter Period 2 where they receive the active nabiximols spray and again undergo a 2-week titration period, and a 4-week consistent daily dosage period.

Drug: Nabiximols; Drug: Placebo

Interventions

Nabiximols DRUG

Nabiximols is is a yellow-brown oromucosal spray solution containing 27 mg/mL of THC and 25 mg/mL of CBD.

Also known as: Sativex

Nabiximols, then Placebo; Placebo, then Nabiximols

Placebo DRUG

The placebo is a matching oromucosal spray that is identical to the investigational study product in terms of packaging, labelling, schedule of administration, dosing instructions, and appearance.

Nabiximols, then Placebo; Placebo, then Nabiximols

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of NMOSD, meeting the International Panel for NMO Diagnosis (IPND) NMOSD criteria (Appendix 1), including NMOSD with AQP4-IgG, and NMOSD without AQP4-IgG
• Aged between 18 years or older, at the time of signing the informed consent
• Willing and able to give informed consent and to participate in all study procedures
• Moderate to severe spasticity, as defined by a score of \> 3 on the 0-10 numerical rating scale for spasticity (NRS-S) at the time of screening
• Reports NMOSD-related spasticity symptoms ongoing for at least 6 months
• Spasticity is determined to be causally related to an NMOSD attack in the opinion of the investigator
• No relapses, and otherwise stable disease (i.e. no significant recovery from relapse or other change in disability) for at least 6 months, in the opinion of the investigator
• Anti-spasticity regimen, if on medications, maintained at a stable dose for the 30 days prior to enrollment without adequate relief of spasticity symptoms.
• Willing to maintain a stable dose of non-study-related anti-spasticity medication for the duration of the study, barring significant changes to their medical condition.
• Willing to allow his or her primary care doctor and primary neurologist, if appropriate, to be notified of participation in the study.
• Documentation of negative MOG-IgG, if diagnosis is NMOSD without AQP4-IgG positive status. Participant with presumptive diagnosis of NMOSD without AQP4-IgG and no prior MOG IgG testing can have MOG testing sent, and be eligible for participation if this is negative.
• For women of childbearing potential: participants who are not lactating, not pregnant, and not planning to become pregnant in the next 8 months and who agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of nabiximols.
• For males with partners who are females of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of nabiximols.
• Able to use the necessary electronic applications (either via smartphone, tablet, or desktop) and has an email address.

You may not qualify if:

• Consumption of cannabis herb or other cannabinoid-based drugs within 30 days prior to study entry.
• Unwillingness to abstain from consumption of cannabis herb or other cannabinoid-based drugs for the duration of the study.
• Known or suspected hypersensitivity or adverse reaction (including psychiatric adverse reactions) to cannabinoids or cannabinoid products, ethanol, peppermint oil or propylene glycol.
• Currently receiving a prohibited medication and unwilling or unable to stop for the duration of the study. Prohibited medications include: CYP3A4 inhibitors: clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, etc.; CYP3A4 inducers: rifampicin, phenobarbital, phenytoin, St. John's Wort. Of note, the CYP3A4 inducer carbamazepine is permitted, but a stable dosage must be maintained throughout the study (no as needed dosing permitted). Other prohibited medications: regular levodopa (Sinemet, Sinemet Plus, Levodopa, L-dopa, Madopar, Benserazide), sildenafil (Viagra), fentanyl, or antiarrhythmic medications.
• Receipt of an investigational medicinal product or participation in a therapeutic clinical trial within 30 days prior to the initial visit
• Received a Botulinum Toxin injection within four months prior to the screening visit or unwillingness to stop receiving Botulinum Toxin injections for the relief of spasticity for the duration of the study.
• Personal medical history of schizophrenia, severe personality disorders, other major psychotic disorders, or other major psychiatric disorders other than depression and anxiety.
• Family history in 1st degree relatives of schizophrenia or other psychotic disorders.
• Hospitalization for depression or anxiety within the 2 years prior to the screening visit.
• A documented history of attempted suicide or suicidal ideation of category 4 or 5 according to the Columbia Suicide Severity Rating Scale (C-SSRS) screening, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt.
• Known or suspected history of a substance use disorder or heavy alcohol consumption excluding tobacco use disorder or cannabis use not meeting criteria for cannabis use disorder.
• History of myocardial infarction or clinically significant ischemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure. .
• Significant renal or hepatic impairment, either in the opinion of the investigator, or by the following laboratory screening values: AST or ALT \> 2 × upper limit of normal (ULN); Total bilirubin \> 2 × ULN (unless due to Gilbert's syndrome); BUN \> 2 × upper limit of normal (ULN)
• History of epilepsy or recurrent seizures.
• Concomitant disease or disorder that has symptoms of spasticity, and that in the opinion of the Investigator may influence the study outcome and endpoint assessment.

Sponsors & Collaborators

• Michael, Levy M.D.,Ph.D.: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Neuromyelitis Optica; Muscle Spasticity; Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Michael Levy, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Anastasia Vishnevetsky, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology at Massachusetts General Hospital

Model Details: This is a phase II, single-site, double-blind, randomized, placebo-controlled 2 by 2 crossover clinical trial designed to evaluate the efficacy of nabiximols compared to placebo for the treatment of NMOSD-related spasticity.

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 3, 2023
• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)