Ozanimod for Multiple Sclerosis

(COAST Trial)

Recruiting at 2 trial locations

Overseen By Lilli Farrell, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Anti-CD20 therapy

Must not be taking: MAO inhibitors, Systemic corticosteroids

Disqualifiers: Progressive MS, Uncontrolled diabetes, Cancer, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 36 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of ozanimod for individuals with stable multiple sclerosis (MS) who have been on anti-CD20 therapy. Ozanimod may assist patients in transitioning from their current treatment while maintaining stability. The trial includes two groups: one will continue their current medication, and the other will switch to ozanimod after a specified period. Individuals with MS symptoms for at least three years and stability without new symptoms for two years may be suitable candidates. As a Phase 4 trial, ozanimod has already received FDA approval and proven effective, and this research aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on an anti-CD20 therapy for at least two years before starting the trial. You cannot use certain medications like monoamine oxidase inhibitors or systemic corticosteroids.

What is the safety track record for ozanimod?

Research has shown that ozanimod is safe for people with relapsing multiple sclerosis. Long-term studies indicate that most people tolerate it well, even after years of use. Importantly, no new safety concerns have emerged compared to earlier studies.

Common side effects might include headaches or fatigue, but serious issues are rare. For those considering joining a trial with ozanimod, these findings suggest it is a safe option for many. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about ozanimod for multiple sclerosis because it offers a novel approach compared to standard treatments like interferons and glatiramer acetate. Unlike these traditional therapies, ozanimod targets specific receptors on immune cells, potentially reducing inflammation more precisely and with fewer side effects. Additionally, ozanimod is administered orally, providing a more convenient alternative to injectable treatments. This combination of targeted action and ease of use could make a significant difference for patients managing multiple sclerosis.

What evidence suggests that ozanimod might be an effective treatment for multiple sclerosis?

Research has shown that ozanimod, which participants in this trial may receive, effectively treats relapsing forms of multiple sclerosis (MS). Studies have found that ozanimod reduces relapses and helps prevent new brain lesions in patients. Long-term evidence indicates it maintains low brain shrinkage over five years. Compared to other oral treatments, ozanimod is safer and works as well or better. This treatment has already proven effective in protecting the brain from MS damage. ^{1 5 6 7 8}

Who Is on the Research Team?

Enrique Alvarez

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsing forms of Multiple Sclerosis (MS) who've been stable on anti-CD20 therapy for at least two years, without new MS activity. They must be able to undergo an MRI and agree to contraception if applicable. Exclusions include recent heart issues, chronic infections like HIV or hepatitis, certain neurological conditions other than MS, pregnancy plans or current pregnancy/lactation, severe liver function impairment, uncontrolled diabetes or other significant medical/psychiatric illnesses.

Inclusion Criteria

Participants must provide written informed consent and be able to comply with the visit schedule and study related assessments

I haven't had new symptoms or flare-ups of my inflammatory disease for at least two years.

I have been diagnosed with relapsing MS and have had symptoms for at least 3 years.

Exclusion Criteria

I have a history of chronic infections like HBV, HCV, or HIV, but UTIs are okay.

I've had a serious heart issue or stroke in the last 6 months.

I am currently taking a monoamine oxidase inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ozanimod as de-escalation therapy from anti-CD20 therapy

36 months

Regular visits every 3 months for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ozanimod

Trial Overview

The study tests the safety and effectiveness of ozanimod as a step-down treatment in clinically stable MS patients previously treated with anti-CD20 therapies. It's a multi-center pilot study where participants will switch from their current treatment to ozanimod.

How Is the Trial Designed?

Group I: Ozanimod de-escalation of anti-CD20 treatment Experimental Treatment 1 Intervention

Ozanimod will be started 6-12 months after the last anti-CD20 infusion, including ocrelizumab subcutaneous injection, or 30-180 days from their last ofatumumab injection. Ozanimod will be provided by the study.

Group II: Continued anti-CD20 treatment Active Control 1 Intervention

Patients will continue to receive anti-CD20. Propensity score matched to the experimental arm.

Ozanimod is already approved in European Union, United States for the following indications:

Approved in European Union as Ozanimod for:

• Moderate to severe active ulcerative colitis

Approved in United States as Ozanimod for:

• Moderate to severe active ulcerative colitis

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a comparison of ozanimod and ponesimod for treating relapsing multiple sclerosis, ozanimod showed a numerically lower annualized relapse rate and a significant reduction in brain volume loss over 2 years, indicating better efficacy in preserving brain health.

Ozanimod also had a significantly lower risk of treatment-emergent adverse events and discontinuation due to adverse events compared to ponesimod, suggesting a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison. Swallow, E., Pham, T., Patterson-Lomba, O., et al.[2023]

In a 24-month phase 3 trial involving 1320 participants with relapsing multiple sclerosis, ozanimod demonstrated a significantly lower annualized relapse rate compared to interferon beta-1a, indicating its efficacy as a treatment.

Ozanimod was well tolerated, with fewer treatment-emergent adverse events leading to discontinuation compared to interferon beta-1a, suggesting it may be a safer oral alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Cohen, JA., Comi, G., Selmaj, KW., et al.[2020]

Ozanimod, an oral sphingosine 1-phosphate receptor modulator, was approved by the US FDA in March 2020 for treating relapsing forms of multiple sclerosis, including clinically isolated syndrome and active secondary progressive disease.

The drug has also received a positive recommendation for approval in the EU and is currently being tested in phase III trials for ulcerative colitis and Crohn's disease, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozanimod: First Approval. Lamb, YN.[2020]

Ozanimod, an oral treatment for relapsing multiple sclerosis, was found to be well tolerated in a large population of 2631 participants over an average of 32 months, with safety results consistent with earlier phase 3 trials.

The incidence rates of treatment-emergent adverse events were similar to those observed in phase 3 trials, with no new safety concerns identified, and serious complications like opportunistic infections and significant heart issues were absent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program. Selmaj, KW., Cohen, JA., Comi, G., et al.[2021]

Ozanimod significantly reduces the annualized relapse rate and the number of gadolinium-enhancing lesions in adults with relapsing forms of multiple sclerosis, based on a meta-analysis of 2917 participants from three randomized controlled trials.

The 1 mg dose of ozanimod is more effective than the 0.5 mg dose in reducing relapse rates and new T2 lesions, without increasing the risk of adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozanimod for Treatment of Relapsing-Remitting Multiple Sclerosis in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sun, Y., Yang, Y., Wang, Z., et al.[2021]

Ozanimod is an effective treatment for multiple sclerosis (MS) that works by selectively modulating S1P1 and S1P5 receptors, preventing harmful immune cells from entering the central nervous system and causing damage.

While ozanimod has been shown to be well tolerated, it does carry risks such as increased infections, liver injury, and other serious side effects, highlighting the need for careful monitoring and further comparative studies with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects. Lassiter, G., Melancon, C., Rooney, T., et al.[2020]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01628393

NCT01628393 | Efficacy and Safety Study of Ozanimod ...

The primary objective in Part A of this study was to demonstrate the superior efficacy of ozanimod compared to placebo.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8123972/

An Overview of the Efficacy and Safety of Ozanimod for the ...

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: results from the DAYBREAK Open-Label Extension Study; 2021.

3.

news.bms.com

news.bms.com/news/details/2024/New-Long-Term-Zeposia-ozanimod-Data-Demonstrate-Durable-Efficacy-and-Consistent-Safety-in-Relapsing-Forms-of-Multiple-Sclerosis/default.aspx

New Long-Term Zeposia (ozanimod) Data Demonstrate ...

These findings showed that patients receiving continuous Zeposia treatment for up to five years experienced low and stable rates of whole brain volume (WBV) ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38855023/

Comparative effectiveness and safety of ozanimod versus ...

Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.

5.

zeposia.com

zeposia.com/multiple-sclerosis/efficacy-and-study-results

ZEPOSIA® (ozanimod) Clinical Study Results

ZEPOSIA is proven to help protect the brain from the damaging effects of MS by reducing relapses and new or enlarging lesions.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35765217/

Long-term safety and efficacy of ozanimod in relapsing ...

This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging ...

7.

zeposiahcp.com

zeposiahcp.com/multiple-sclerosis/clinical-data/safety

ZEPOSIA® (ozanimod) MS Safety Profile | HCPs

See ZEPOSIA® safety profile and adverse reactions data in Relapsing Multiple Sclerosis clinical trials. See full safety and Prescribing Information.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2211034821001103

Ozanimod in relapsing multiple sclerosis: Pooled safety ...

Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.