Ozanimod for Multiple Sclerosis

(ENLIGHTEN Trial)

No longer recruiting at 126 trial locations

Overseen By Mary Ann Picone, Site 149

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Celgene

Must be taking: Ozanimod

Disqualifiers: Hepatic disease, Neurologic disorders, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ozanimod for individuals with relapsing multiple sclerosis (RMS), a condition where the immune system mistakenly attacks the protective covering of nerves. The main goal is to determine if ozanimod can improve the brain's information processing speed after three years. Participants must have received an RMS diagnosis within the last five years and should not have used more than one disease-modifying therapy for their condition. Eligible participants will take an oral dose of ozanimod daily throughout the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you can only have received one or fewer disease-modifying therapies for multiple sclerosis to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that ozanimod is generally safe for people with relapsing multiple sclerosis (RMS). Studies have found that most patients complete their treatment without major problems. In large trials, about 90% of patients finished their treatment with ozanimod.

Additionally, a long-term study found no new safety issues, indicating that it remains safe over time. Common side effects are usually mild, such as headaches or colds, and serious side effects are rare. Overall, the evidence supports ozanimod as a safe choice for treating RMS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple sclerosis, such as interferons and glatiramer acetate, which are injected, Ozanimod (RPC-1063) offers a convenient oral administration. Researchers are excited about this treatment because it targets the sphingosine-1-phosphate (S1P) receptor, modulating immune response to reduce inflammation and nerve damage. This mechanism could potentially lead to fewer relapses and better disease management, with a possibly improved side effect profile.

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

Research shows that ozanimod, administered in this trial as RPC-1063, effectively treats relapsing multiple sclerosis (RMS). Studies have found that ozanimod reduces relapses and helps maintain brain size over time. Compared to other treatments, ozanimod is generally safe and offers similar or better symptom management. Long-term evidence suggests benefits can last up to five years. Overall, ozanimod protects the brain from MS damage by reducing relapses and preventing new or growing lesions. ^{4 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Relapsing Multiple Sclerosis (RMS) diagnosed within the last 5 years. Participants should have an EDSS score of ≤3.5, can adhere to the study schedule, and have taken no more than one disease-modifying therapy (DMT). Those with other neurological disorders, significant visual or sensorimotor impairments, developmental disorders like ADHD, or major systemic diseases are excluded.

Inclusion Criteria

I have been diagnosed with MS according to recent standards.

There are more requirements to be included in the study besides the ones listed.

Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.

Exclusion Criteria

I have a neurological disorder that could explain my worsening neurological condition or affect my thinking.

You have a history of conditions that affect how you learn or pay attention, like ADHD or learning disabilities.

I do not have major health issues that would risk my participation in the study, except for mild or moderate asthma or COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orally administered ozanimod HCl 1 mg to assess changes in cognitive processing speed over 3 years

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including a 30-day and 90-day safety follow-up visit

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RPC-1063

Trial Overview The study tests how ozanimod HCl 1 mg affects cognitive processing speed in RMS patients over three years. The main goal is to see if subjects show a meaningful improvement in their SDMT scores from baseline after treatment. All participants will take ozanimod orally and attend follow-up safety visits post-treatment.

How Is the Trial Designed?

Group I: Administration of RPC-1063 Experimental Treatment 1 Intervention

Patients with relapsing MS will receive RPC-1063 orally:

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

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]

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 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. 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.

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. 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.

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. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33892317/

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 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2211034821001103

Ozanimod in relapsing multiple sclerosis: Pooled safety ... Ozanimod was generally well tolerated, with completion rates of approximately 90% in the pivotal phase 3 trials. Both doses of ozanimod demonstrated a favorable ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9493410/

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 ...