Ocrelizumab vs Fingolimod for Pediatric Multiple Sclerosis

(Operetta 2 Trial)

Not currently recruiting at 257 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, ocrelizumab and fingolimod, to determine which is more effective for children and teens with relapsing-remitting multiple sclerosis (RRMS). The goal is to assess the safety and effectiveness of these medications in managing the condition. Participants will receive either ocrelizumab through IV infusions or take fingolimod orally. Children and teens diagnosed with RRMS, who experience frequent relapses, and weigh at least 25 kilograms may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found that ocrelizumab was well-tolerated, with no unexpected side effects. It has been tested in over 1,300 patients with multiple sclerosis (MS), and the side effects are well-documented, with no new ones reported.

Research has shown that fingolimod is generally well-tolerated in children with MS. Common side effects include temporary low levels of a type of white blood cell, cough, and urinary tract infections. One study reported that 88.8% of children taking fingolimod experienced some side effects, but these were mostly mild.

Both treatments have been extensively studied, providing ample safety information. These findings can reassure those considering joining a trial about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pediatric multiple sclerosis because they offer distinct approaches compared to existing options. Ocrelizumab is unique because it works by targeting and depleting certain immune cells known as CD20-positive B cells, which are believed to play a key role in the progression of multiple sclerosis. This mechanism is different from most standard treatments, which primarily focus on modulating the immune response rather than depleting specific cells. On the other hand, Fingolimod is already an active comparator and works by retaining certain types of immune cells in the lymph nodes, preventing them from reaching the central nervous system and causing damage. These contrasting approaches might provide more tailored options for young patients, potentially improving outcomes and expanding treatment possibilities.

What evidence suggests that this trial's treatments could be effective for pediatric multiple sclerosis?

This trial will compare Ocrelizumab and Fingolimod for pediatric multiple sclerosis. Research has shown that Ocrelizumab, which participants in this trial may receive, reduces the number of relapses and stabilizes disability levels in people with relapsing multiple sclerosis (MS), including children. It also slows the worsening of disability over time. Similarly, Fingolimod, another treatment option in this trial, effectively treats relapsing MS in children by managing symptoms and preventing relapses. Studies have found that Fingolimod is among the most commonly used treatments for pediatric MS, alongside other effective therapies. Both treatments show promise in managing MS symptoms and slowing the disease's progression in young patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 Development, LP

Industry Sponsor

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. tascenso.com tascenso.com/hcp/what-is-tascenso-odt/bioequivalence/

Efficacy and Safety TASCENSO ODT is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10170592/

Narrative review based on fingolimod therapy in pediatric MS A recent study from Turkey found higher rates: 13% of the patients were under fingolimod treatment, amounting to 38% of the nDMD users.

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/214962s000lbl.pdf

TASCENSO ODT (fingolimod) - accessdata.fda.gov Pediatric Use. Safety and effectiveness of fingolimod for the treatment of relapsing forms of multiple sclerosis in pediatric patients 10 to less than. 18 ...

4. tascenso.com tascenso.com/generic-fingolimod/

Research Connects MS Relapse with Subpotent Generic ... Relapse rate was higher during treatment with generic fingolimod capsules, relative to when on Gilenya® capsules. • The average time from treatment start to a ...

5. managedhealthcareexecutive.com managedhealthcareexecutive.com/view/highly-effective-therapies-found-superior-to-moderately-effective-therapies-as-first-line-treatment-in-pediatric-ms

Highly Effective Therapies Found Superior to Moderately ... Fingolimod and Tysabri were the most commonly used highly effective therapies. The study's primary outcome was the time to first relapse after ...

6. fda.gov fda.gov/media/181806/download

Gilenya Pediatric Postmarketing Safety Review This review evaluates FDA Adverse Event Reporting System (FAERS) reports for Gilenya. (fingolimod) and Tascenso ODT (fingolimod) in pediatric ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6858833/

Review Of The Safety, Efficacy And Tolerability Of Fingolimod ... Of the side effects that were observed, there were transient cases of lymphopenia and cough, as well as urinary tract infection and leg ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1800149

Trial of Fingolimod versus Interferon Beta-1a in Pediatric ... Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received ...

9. neurologylive.com neurologylive.com/view/safety-and-efficacy-of-fingolimod-for-pediatric-ms

Safety and Efficacy of Fingolimod for Pediatric MS This study demonstrated an 82% superiority of fingolimod over interferon beta-1a in reducing relapses over a 2-year period. Overall, the study ...