Nabiximols for Neuromyelitis Optica Spectrum Disorder

(SENS-NMO Trial)

Overseen By Rebecca Salky

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Michael, Levy M.D.,Ph.D.

Must be taking: Anti-spasticity medications

Must not be taking: Cannabinoids, CYP3A4 inhibitors, others

Disqualifiers: Cannabis use, Schizophrenia, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a spray called nabiximols can reduce muscle stiffness in individuals with neuromyelitis optica spectrum disorder (NMOSD). The study will assess whether nabiximols improves symptoms such as pain, muscle spasms, mood, walking, and sleep compared to a placebo, which contains no active drug. Participants will receive treatments by mail and complete most study activities online, with an optional in-person sub-study. Individuals who have experienced NMOSD-related muscle stiffness for at least six months and meet other specific criteria may be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important early-stage findings.

Will I have to stop taking my current medications?

The trial requires that you maintain a stable dose of any non-study-related anti-spasticity medication you are currently taking. However, you must stop taking certain medications like some antibiotics, antifungals, and other specific drugs listed in the exclusion criteria for the duration of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nabiximols, a spray made from cannabis, has been tested in people before. It is already used to help with muscle stiffness in individuals with multiple sclerosis, a condition affecting the brain and spinal cord. In these past studies, many participants tolerated nabiximols well.

Some experienced mild side effects such as dizziness, fatigue, or dry mouth, which were usually not serious. This suggests nabiximols might be safe for treating muscle stiffness in conditions like NMOSD as well. However, reactions can vary, so consulting a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NMOSD?

Nabiximols is unique because it's derived from cannabis and delivered via an oromucosal spray, offering a new approach for treating neuromyelitis optica spectrum disorder (NMOSD). Unlike current treatments like immunosuppressants and monoclonal antibodies, nabiximols combines THC and CBD, which may modulate the immune response and reduce inflammation in a novel way. Researchers are excited because this new mechanism of action could offer relief for patients who don't respond well to existing therapies, potentially improving their quality of life significantly.

What evidence suggests that nabiximols might be an effective treatment for NMOSD?

Studies have shown that nabiximols, a spray made from cannabis compounds, can reduce muscle stiffness in people with conditions like multiple sclerosis (MS). Real-world data from over 1,000 MS patients demonstrated that nabiximols improved their symptoms. Nabiximols interact with the body's system that controls muscle tone and movement. In this trial, participants will receive nabiximols in one period and a placebo in another to evaluate its effectiveness in treating muscle stiffness in neuromyelitis optica spectrum disorder (NMOSD). Although research is ongoing, early findings suggest nabiximols may help NMOSD patients, potentially improving their quality of life. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael Levy, MD, PhD

Principal Investigator

Massachusetts General Hospital

Anastasia Vishnevetsky, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults diagnosed with Neuromyelitis Optica Spectrum Disorders (NMOSD) who experience moderate to severe spasticity for at least 6 months can join. They must be stable on current medications, not planning pregnancy, and able to use electronic devices for remote study participation. Exclusions include certain psychiatric conditions, substance abuse history, significant heart or liver issues, recent cannabis use, and known allergies to trial medication components.

Inclusion Criteria

I agree to use contraception or remain abstinent for 3 months after my last dose.

My condition has been stable with no relapses for at least 6 months.

Able to use the necessary electronic applications (either via smartphone, tablet, or desktop) and has an email address

Exclusion Criteria

I do not have severe kidney or liver problems.

My immediate family has a history of schizophrenia or similar conditions.

Intention to travel internationally during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (virtual)

Treatment Period 1

Participants receive either nabiximols or placebo spray with a 2-week dose escalation followed by a 4-week stable treatment period

6 weeks

4 visits (virtual)

Washout

Participants undergo a 2-week washout period between treatment periods

2 weeks

Treatment Period 2

Participants receive the alternate treatment (nabiximols or placebo) with a 2-week dose escalation followed by a 4-week stable treatment period

6 weeks

4 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Nabiximols

Trial Overview The trial is testing nabiximols (a cannabinoid spray) against a placebo in treating spasticity from NMOSD. It aims to see if nabiximols improve symptoms like muscle stiffness, pain frequency of spasms, mood swings walking ability and sleep quality compared to a dummy spray. Participants will receive treatments by mail and complete questionnaires remotely.

How Is the Trial Designed?

Group I: Placebo, then Nabiximols Experimental Treatment 2 Interventions

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.

Group II: Nabiximols, then Placebo Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Michael, Levy M.D.,Ph.D.

Lead Sponsor

Trials

1

Recruited

40+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05974293

A Phase IIb Study of Nabiximols for Spasticity Due ... The goal of this study is to evaluate the safety and efficacy of nabiximols spray, for the treatment of moderate to severe spasticity in adult patients with ...

2. rarediseaseadvisor.com rarediseaseadvisor.com/features/neurologists-plan-historic-trial-cannabinoid-spray-nabiximols-nmosd/

Neurologists Plan Historic Trial of Cannabinoid Spray for ... A phase 2b clinical trial for nabiximols, a cannabinoid spray, to treat spasticity in 44 patients with NMOSD.

3. withpower.com withpower.com/trial/phase-2-muscle-spasticity-3-2024-61291

Nabiximols for Neuromyelitis Optica Spectrum Disorder ... This trial tests a cannabinoid spray called nabiximols to help adults with a condition affecting the nervous system who have severe muscle stiffness.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9539865/

A real‐world evidence study of nabiximols in multiple ... We analyzed real‐world data from the Italian Medicines Agency e‐Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05974293?keyword=%22Cannabinoid%22

A Phase IIb Study of Nabiximols for Spasticity Due to ... The goal of this study is to evaluate the safety and efficacy of nabiximols spray, for the treatment of moderate to severe spasticity in adult patients with ...

6. go.drugbank.com go.drugbank.com/conditions/DBCOND0067761

Neuromyelitis Optica Spectrum Disorders ... Associated Data ; NCT04155424. A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder.