Ozanimod for Multiple Sclerosis

Recruiting at 2 trial locations

Overseen By Deja Leadley, 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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

A multi-center pilot study to evaluate safety and efficacy of ozanimod as de-escalation therapy in clinically stable MS patients previously treated with anti-CD20 therapy.

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 data supports the effectiveness of the drug Ozanimod for treating multiple sclerosis?

Research shows that Ozanimod significantly reduces the rate of relapses and the number of new or enlarging brain lesions in people with relapsing forms of multiple sclerosis. It is also well tolerated, with fewer adverse events compared to some other treatments. ^{1 2 3 4 5}

Is Ozanimod safe for humans?

Ozanimod is generally well tolerated in humans, but it can increase the risk of infections, liver injury, high blood pressure, and other complications. It has been approved for treating multiple sclerosis and is being studied for other conditions, showing a favorable safety profile in clinical trials. ^{1 2 3 4 6}

What makes the drug Ozanimod unique for treating multiple sclerosis?

Ozanimod is unique because it is an oral medication that selectively targets specific receptors (S1P1 and S1P5) to prevent harmful immune cells from entering the central nervous system, reducing nerve damage and inflammation. This targeted approach helps minimize side effects compared to other treatments. ^{1 2 3 4 5}

Research Team

Enrique Alvarez

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

I am currently taking a monoamine oxidase inhibitor.

Timeline

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

Treatment Details

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.

Participant Groups

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 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+

Findings from Research

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]

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 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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ozanimod: First Approval. [2020]

3. Switzerland 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects. [2020]

5. England 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. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program. [2021]