Ozanimod for Multiple Sclerosis

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Enrique Alvarez

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

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}

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.

Trial 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 (Sphingosine-1-phosphate receptor modulator)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Colorado Anschutz Medical Campus Aurora, CO

Cleveland Clinic Las Vegas, NV

Cleveland Clinic Cleveland, OH

Who Is Running the Clinical Trial?

University of Colorado, Denver Lead Sponsor

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] Ozanimod and ponesimod are sphingosine 1-phosphate receptor modulators approved by the U.S. Food and Drug Administration for treatment of relapsing forms of multiple sclerosis (MS). Given that no head-to-head trials have assessed these two treatments, we performed a matching-adjusted indirect comparison (MAIC) to compare efficacy and safety outcomes between ozanimod and ponesimod for MS.

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

Ozanimod: First Approval. [2020] Ozanimod (ZEPOSIA®; Celgene Corporation) is a novel, orally administered sphingosine 1-phosphate (S1P) receptor modulator. In March 2020, the US FDA approved ozanimod capsules for use in the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. In the same month, ozanimod received a positive CHMP opinion recommending approval in the EU for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Ozanimod is currently being evaluated for use in ulcerative colitis and Crohn's disease in multinational phase III trials. This article summarizes the milestones in the development of ozanimod leading to its first approval for relapsing forms of multiple sclerosis.

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] Background: Ozanimod has been approved for use in the treatment of relapsing forms of multiple sclerosis by the United States FDA. As a novel, orally available sphingosine 1-phosphate receptor modulator, ozanimod selectively binds to S1P1 and S1P5 receptor with high affinity, minimizing safety concerns caused by S1P3 receptor activation. Methods: e systematically searched PUBMED, EMBASE database, and Cochrane Library database to identify randomized controlled trials (RCTs) from inception to June 28, 2020. Trials were considered eligible if they 1) were randomized clinical trials (RCTs); 2) enrolled adult participants diagnosed with Relapsing-remitting MS; 3) compared ozanimod with placebo or any other approved DMDs that evaluated in phase III or phase II clinical trials; 4) enrolled over 100 participants; 5) provided any available information for predefined primary or secondary outcomes. Results: 2917 participants from three high-quality, multi-centered randomized clinical trials were pooled in our analysis. We found that using ozanimod was significantly associated with the reduction of the annualized relapse rate during the treatment period (RR, -0.10 [95% CI, -0.15, -0.06]). Also, the decreased number of gadolinium-enhancing lesions at the end of the trial was relative to the treatment of ozanimod (ozanimod, 0.29; control, 0.65; RR, -0.20 [95% CI, -0.34, -0.06]). Compared with patients in the control group, the number of new or enlarging T2 lesions over the treatment period decreased in patients treated with ozanimod (ozanimod, 1.82; control, 3.55; RR, -1.12 [95% CI, -1.52, -0.71]). As to the safety endpoints, patients in the ozanimod group reported a lower rate of adverse events (ozanimod, 66.03%; control, 77.07%; RR, 0.64 [95% CI, 0.43, 0.95]). Similar incidence of infection-related TEAEs was found across treatment groups (nasopharyngitis: ozanimod, 11.19%; control, 9.83%; RR, 1.10 [95% CI, 0.77-1.57]; urinary-tract infection: ozanimod, 3.81%; control, 2.97%; RR, 1.29 [95% CI, 0.83-2.00]). No case of macular edema was noted as well as second-degree, type 2, or third-degree atrioventricular block. As for the subgroup analysis, compared with 0.5 mg ozanimod, 1 mg ozanimod is related with a significant reduction of the annualized relapse rate during the treatment period (1 mg ozanimod, 0.18; 0.5 mg ozanimod, 0.24; RR, 0.05 [95% CI, 0.01, 0.09])and a decreased number of new or enlarging T2 lesions over the treatment period (1 mg ozanimod,1.58; 0.5 mg ozanimod, 2.05; RR, 0.49 [95% CI, 0.19, 0.79]). No significant difference in causing adverse events between 1 and 0.5 mg was found. Conclusions: Our meta-analysis found that, with favorable safety performance, the use of ozanimod as a treatment of relapsing-remitting multiple sclerosis in adults was associated with a significant reduction of the annualized relapse rate during the treatment period, decreased number of gadolinium-enhancing lesions at the end of the trial, and lowered number of new or enlarging T2 lesions over the treatment period. Ozanimod 1 mg outperformed 0.5 mg dose in efficacy without increasing the risk of adverse events.

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] Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing-remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

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] Ozanimod is a sphingosine 1-phosphate receptor modulator, which selectively binds to sphingosine 1-phosphate receptor subtypes 1 and 5 with high affinity. In the RADIANCE phase 2 study in participants with relapsing multiple sclerosis, ozanimod was associated with better efficacy than placebo on MRI measures and was well tolerated. The RADIANCE phase 3 study aimed to confirm the safety and efficacy of ozanimod versus interferon beta-1a in individuals with relapsing multiple sclerosis.

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

Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program. [2021] Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.