Ocrelizumab vs Fingolimod for Pediatric Multiple Sclerosis

(Operetta 2 Trial)

Recruiting at 219 trial locations

Overseen By Reference Study ID Number: WN42086 https://forpatients.roche.com/

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Disqualifiers: Other neurologic disorders, uncontrolled somatic diseases, severe cardiac disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

171 Participants Needed

Trial Summary

What is the purpose of this trial?

This double-blind, double-dummy study will evaluate the safety and efficacy of ocrelizumab compared with fingolimod in children and adolescents with RRMS aged between 10 and \< 18 years over a flexible duration. The double-blind period will last until after the last participant randomized has completed 24 weeks.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug fingolimod for pediatric multiple sclerosis?

Fingolimod has been shown to be effective for children with relapsing-remitting multiple sclerosis, as it is the only FDA and European Medicines Agency approved drug for this condition. Studies and case reports have demonstrated its ability to stabilize the disease and reduce relapse rates in pediatric patients. ^{1 2 3 4 5}

Is fingolimod safe for use in pediatric multiple sclerosis?

Fingolimod, also known as Gilenya, has been approved for use in children with relapsing multiple sclerosis and has been shown to be generally safe, though it may cause side effects like heart issues, infections, and eye problems. Long-term studies have confirmed its safety profile, but monitoring is recommended, especially after the first dose. ^{1 2 5 6 7}

How does the drug Ocrelizumab differ from other treatments for pediatric multiple sclerosis?

Ocrelizumab is unique because it targets a specific type of immune cell called B-cells, which are involved in the immune response that damages the nervous system in multiple sclerosis. This is different from other treatments like fingolimod, which works by trapping immune cells in the lymph nodes to prevent them from reaching the brain and spinal cord. ^{1 2 5 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for children and adolescents aged 10 to under 18 with relapsing-remitting multiple sclerosis (RRMS). They must weigh at least 50 kg, have had recent MS activity, and be neurologically stable. It's not for those with other neurological conditions that look like MS, uncontrolled diseases, active infections, or severe heart issues.

Inclusion Criteria

My disability level allows me to walk without aid or rest for at least 200 meters.

I have been diagnosed with RRMS according to recognized medical standards.

My neurological condition has been stable for over a month.

Exclusion Criteria

I might have or am suspected to have a neurological condition similar to MS.

I do not have any severe illnesses or infections that would stop me from joining the study.

I have severe heart problems or abnormal heart test results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either ocrelizumab by IV infusion every 24 weeks or fingolimod orally daily, with a placebo of the other treatment

24 weeks

IV infusion on Days 1 and 15, then every 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension (optional)

Participants may opt into continuation of ocrelizumab treatment for at least 144 weeks

144 weeks

Treatment Details

Interventions

• Fingolimod
• Ocrelizumab

Trial Overview The study compares the safety and effectiveness of two drugs: Ocrelizumab and Fingolimod. Participants will receive either one of these drugs or a placebo without knowing which one they are getting. The trial will last at least 96 weeks.

Participant Groups

Group I: Ocrelizumab Experimental Treatment 2 Interventions

Participants will receive ocrelizumab by intravenous (IV) infusion every 24 weeks (Q24W). The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15 and subsequent doses are given as single infusions of ocrelizumab Q24W. Participants will also receive a placebo of fingolimod administered as once a day (QD) capsule.

Group II: Fingolimod Active Control 2 Interventions

Participants will receive fingolimod orally (PO) QD as per the prescribing information provided with fingolimod. Participants will also receive a placebo of ocrelizumab administered as IV infusion on Days 1 and 15, and Q24W thereafter.

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

Approved in European Union as Gilenya for:

• Relapsing forms of multiple sclerosis

Approved in United States as Gilenya for:

• Relapsing forms of multiple sclerosis

Approved in Canada as Gilenya for:

• Relapsing forms of multiple sclerosis

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Findings from Research

Fingolimod (Gilenya®) has been approved for treating relapsing-remitting multiple sclerosis (MS) in children, with real-world data from two cases showing its effectiveness over more than 2 years of treatment.

The findings support the use of fingolimod as a viable therapeutic option for pediatric patients with active relapsing MS, highlighting its potential benefits in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingolimod as an effective therapeutic strategy for pediatric relapsing-remitting multiple sclerosis: two case reports. Zanetta, C., Filippi, M., Moiola, L.[2021]

Fingolimod (Gilenya®) is currently the only FDA and EMA approved treatment for pediatric-onset multiple sclerosis (POMS), which accounts for 3-5% of all MS cases, highlighting its significance in managing this condition.

The drug has shown efficacy in adult-onset MS and has been evaluated in POMS through three observational studies and one pivotal clinical trial, indicating its potential effectiveness and safety in younger patients with this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review Of The Safety, Efficacy And Tolerability Of Fingolimod In The Treatment Of Pediatric Patients With Relapsing-Remitting Forms Of Multiple Sclerosis (RRMS). Feng, J., Rensel, M.[2020]

A 14-year-old girl with pediatric-onset multiple sclerosis (POMS) switched from interferon β-1a to fingolimod after 12 months due to worsening symptoms, and she subsequently achieved clinical stability and minimal radiologic activity.

This case supports the effectiveness and safety of fingolimod as a second-line therapy for pediatric MS, aligning with previous studies that suggest it may be beneficial for patients who do not respond adequately to first-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fingolimod after switching from interferon β-1a in an adolescent with multiple sclerosis: case report. Amidei, A., Siciliano, G., Pasquali, L.[2021]

Fingolimod (0.5 mg) is the first oral therapy approved for relapsing forms of multiple sclerosis (MS), showing a significant reduction in relapses by about 50% compared to placebo and intramuscular IFN-β1a over extensive clinical trials.

With over 63,000 MS patients monitored for more than 73,000 patient-years, fingolimod has established a well-characterized safety profile, with manageable side effects through proper patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingolimod for the treatment of relapsing multiple sclerosis. Singer, BA.[2015]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Fingolimod as an effective therapeutic strategy for pediatric relapsing-remitting multiple sclerosis: two case reports. [2021]

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

Review Of The Safety, Efficacy And Tolerability Of Fingolimod In The Treatment Of Pediatric Patients With Relapsing-Remitting Forms Of Multiple Sclerosis (RRMS). [2020]

3. England pubmed.ncbi.nlm.nih.gov

Therapy of highly active pediatric multiple sclerosis. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Childhood multiple sclerosis: clinical features and recent developments on treatment choices and outcomes. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of fingolimod after switching from interferon β-1a in an adolescent with multiple sclerosis: case report. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Comparative safety and efficacy of ozanimod versus fingolimod for relapsing multiple sclerosis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Fingolimod in the treatment of relapsing-remitting multiple sclerosis: long-term experience and an update on the clinical evidence. [2023]

8. Italy pubmed.ncbi.nlm.nih.gov

Fingolimod in pediatric multiple sclerosis: three case reports. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Fingolimod for the treatment of relapsing multiple sclerosis. [2015]