Ofatumumab + Siponimod vs Fingolimod for Pediatric Multiple Sclerosis

(NEOS Trial)

Not currently recruiting at 112 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Progressive MS, Chronic immune 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, ofatumumab and siponimod, compared to fingolimod for children and teens with multiple sclerosis (MS), a condition where the immune system attacks the protective covering of nerves. The goal is to determine which treatment is safest and most effective at preventing MS attacks and managing symptoms. Participants will take medication either orally or as an injection. Children and teens who have experienced at least one MS attack in the past year and do not have other immune system diseases might be suitable for this trial. 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.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Do I need to stop my current medications to join the trial?

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

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

Research has shown that ofatumumab is usually well-tolerated. In a small group of children with multiple sclerosis, it appeared to help with few problems. However, limited information exists about its long-term safety in children. In adults with relapsing MS, 24.7% reported mild to moderate side effects after prolonged use.

Studies have found that siponimod can work well in adults with multiple sclerosis. However, its safety in children remains largely unknown. Some adults might experience side effects, particularly those with liver issues or who receive certain vaccines.

Both treatments are undergoing testing to ensure safety and effectiveness for children with multiple sclerosis. As they are in Phase 3 trials, some evidence of safety exists, but more research is needed for children. ^{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 each offer unique advantages over existing options. Ofatumumab stands out because it targets CD20, a specific protein on B cells, potentially leading to more precise immune modulation compared to other therapies. Siponimod is special due to its ability to selectively modulate the sphingosine-1-phosphate (S1P) receptor, offering a tailored approach that might improve safety and efficacy. Fingolimod, already well-known, is being revisited to compare its performance directly against these new contenders, particularly in a pediatric context. The combination of these treatments could pave the way for more personalized and effective care for young patients with multiple sclerosis.

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

Research has shown that ofatumumab, a treatment under study in this trial, can significantly lower relapse rates and reduce disease activity in children with multiple sclerosis (MS). In one study, only 12% of patients experienced relapses after 12 months of treatment. Siponimod, another treatment option in this trial, has also effectively managed MS, with evidence indicating it can lower the risk of cognitive decline. Both ofatumumab and siponimod offer promising options for treating pediatric MS, potentially reducing symptoms and slowing disease progression. ^{1 3 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged 10 to less than 18 with multiple sclerosis (MS). They should have had at least one MS attack in the past year or two attacks in the last two years, or new brain lesions on MRI within a year. Those with progressive MS, other immune diseases, severe heart or kidney problems can't join.

Inclusion Criteria

I have had at least one MS flare-up in the last year or two in the last two years, or new brain lesions.

I am between 10 and 17 years old.

Exclusion Criteria

I have severe kidney problems.

Participants meeting the definition of ADEM

My MS is getting worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Core Part

24-month, double-blind, triple dummy, randomized, 3-arm active-controlled study in children/adolescent patients with Multiple Sclerosis

24 months

Regular visits as per study protocol

Extension Part

60-month open label treatment for patients who complete the Core Part of the study

60 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Fingolimod
• Ofatumumab
• Siponimod

Trial Overview The study tests Ofatumumab and Siponimod against Fingolimod, all drugs for MS. Participants will be randomly assigned to receive either one of these drugs or their placebos to compare effectiveness and safety.

How Is the Trial Designed?

Group I: siponimod - 0.5 mg, 1 mg or 2 mg/ placebo Experimental Treatment 2 Interventions

Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).

Group II: ofatumumab - 20 mg injection/ placebo Experimental Treatment 2 Interventions

Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).

Group III: fingolimod - 0.5 mg or 0.25 mg/ placebo Active Control 2 Interventions

Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).

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?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

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 is an effective oral treatment for relapsing forms of multiple sclerosis, showing significant reductions in relapse rates and MRI progression compared to placebo and other treatments like IFN-β.

While generally well tolerated, fingolimod can cause common side effects such as fatigue and headaches, and rare but serious risks like heart issues and infections, necessitating careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis. Ward, MD., Jones, DE., Goldman, MD.[2015]

Siponimod has been shown to be statistically significantly more effective than interferon beta-1a and interferon beta-1b in delaying confirmed disability progression in patients with secondary progressive multiple sclerosis, based on a matching-adjusted indirect comparison of individual patient data from the EXPAND trial.

While siponimod demonstrated numerical superiority in reducing annualized relapse rates compared to other disease-modifying treatments, it was not statistically significant except when compared to natalizumab, indicating its potential as a strong option for managing SPMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect treatment comparison of siponimod and other disease modifying treatments in secondary progressive multiple sclerosis. Samjoo, IA., Worthington, E., Haltner, A., et al.[2021]

Ofatumumab is an all-human monoclonal antibody that effectively reduces the frequency of exacerbations and the risk of disability progression in patients with multiple sclerosis, showing better results compared to teriflunomide.

This drug can be used as a second-line therapy for patients with active relapsing MS or secondary progressive MS, especially for those who have not responded to first-line treatments or have a high risk of progressive multifocal leukoencephalopathy (PML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ofatumumab - a new drug for the treatment of multiple sclerosis]. Boyko, AN., Smirnova, NF., Shchukin, IA., et al.[2021]

Ofatumumab (Kesimpta®) is an effective treatment for relapsing forms of multiple sclerosis, showing superior results compared to oral teriflunomide in reducing relapse rates and MRI-detected lesions in two phase III trials.

The treatment has a manageable safety profile, with common side effects like nasopharyngitis and headaches, and no significant increase in serious infections over 3.5 years, making it a convenient self-administered option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ofatumumab: A Review in Relapsing Forms of Multiple Sclerosis. Kang, C., Blair, HA.[2022]

Ofatumumab, a self-administered anti-CD20 antibody for relapsing multiple sclerosis, was well tolerated by patients, with 72% reporting no side effects after initial application and 87% finding the medication easy to handle.

The study, involving 99 out of 127 patients over an average treatment duration of 9.8 months, indicated that side effects were generally mild, with no increased risk of infections, suggesting Ofatumumab is a safe and effective treatment option in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Over one year of B‑cell targeted therapy with Ofatumumab s.c.: first results of a prospective, patient-centered real-world observational study]. Klimas, R., Karl, AS., Poser, PL., et al.[2023]

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]

In a study of 83 pediatric patients receiving chemotherapy, the use of fosaprepitant combined with granisetron significantly reduced vomiting events during both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV) compared to a control group, indicating its efficacy as an antiemetic.

The safety profile of fosaprepitant was comparable to the control group, with no significant differences in adverse events, suggesting it is a well-tolerated option for managing CINV in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety And Feasibility Of Antiemetic Prophylaxis With Fosaprepitant, Granisetron And Dexamethasone In Pediatric Patients With Hemato-Oncological Malignancies. Cabanillas Stanchi, KM., Ebinger, M., Hartmann, U., et al.[2022]

Fosaprepitant, an intravenous prodrug of aprepitant, has been shown to be well tolerated in healthy subjects and provides similar anti-emetic effects as oral aprepitant, making it a promising alternative for preventing chemotherapy-induced nausea and vomiting (CINV).

Clinical studies indicate that fosaprepitant 115 mg is bioequivalent to aprepitant 125 mg, supporting its potential use as part of a 3-day regimen for CINV prevention, although further research is needed to optimize dosing and confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Navari, RM.[2019]

Current pediatric guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) in children primarily recommend a serotonin 5-HT(3) receptor antagonist combined with a corticosteroid, but lack robust evidence and do not include many effective agents used in adults.

The review highlights the need for alternative antiemetic options for children who cannot tolerate or do not respond to standard treatments, discussing both established and emerging therapies like metopimazine, nabilone, and acupuncture, which may offer additional relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing emetic control in children receiving antineoplastic therapy: beyond the guidelines. Dupuis, LL., Nathan, PC.[2021]

A study involving 39 pediatric patients aged 10 months to 18 years showed that fosaprepitant, administered at 4 mg/kg, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), with 89% of patients achieving complete control during the acute phase.

Fosaprepitant appears to be safe for use in young patients, as it demonstrated a significant reduction in emesis and nausea, with 63% control during the delayed phase and an overall incidence of nausea at 43%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Use of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients. Timaeus, S., Elder, J., Franco, K.[2019]

In a study involving 2615 patients with relapsing-remitting multiple sclerosis, fingolimod (Gilenya) was associated with a low incidence of macular edema (ME), with only 19 confirmed cases observed, primarily in those receiving the higher dose of 1.25 mg.

Patients with a history of uveitis were found to be at a higher risk for developing ME, highlighting the importance of pre-treatment ophthalmic evaluations and ongoing eye monitoring during fingolimod therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Zarbin, MA., Jampol, LM., Jager, RD., et al.[2022]

Ofatumumab significantly reduces the annualized relapse rate (ARR) to 0.05 and shows low levels of disease activity in relapsing multiple sclerosis (RMS), with 78.8% of patients meeting criteria for 'no evidence of disease activity' over 4 years.

In terms of safety, while infections were the most common adverse events reported (58.35%), no new safety concerns were identified, indicating a favorable long-term benefit-risk profile for ofatumumab compared to teriflunomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of four-year ofatumumab treatment in relapsing multiple sclerosis: The ALITHIOS open-label extension. Hauser, SL., Zielman, R., Das Gupta, A., et al.[2023]

The combination of netupitant and palonosetron is effective in preventing both acute and delayed nausea and vomiting caused by moderately and highly emetogenic chemotherapy, as supported by phase II and III clinical trials.

This treatment offers a convenient single-capsule dosage and has a favorable side effect profile, although its high cost and administration logistics may pose challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of netupitant and palonosetron in chemotherapy-induced nausea and vomiting. Abramovitz, RB., Gaertner, KM.[2018]

Fingolimod (Gilenya) is the first oral disease-modifying treatment approved for patients with highly active relapsing-remitting multiple sclerosis, marking a significant advancement in MS therapy.

This new treatment offers a novel mechanism of action by modulating the immune system, which may improve patient outcomes compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingolimod for multiple sclerosis. [2015]

Citations

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Ofatumumab in pediatric multiple sclerosis: a case series Ofatumumab showed favorable tolerability and potential benefit in this small pediatric MS cohort. Its subcutaneous administration offers ...

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Ofatumumab in pediatric multiple sclerosis: a case series - PMC A 2024 multicenter retrospective analysis involving pediatric MS indicated that RTX significantly lowered the annual relapse rate and reduced ...

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New Novartis data further support benefits of Kesimpta® in ... ARTIOS Phase IIIb, open-label, single-arm, prospective study showed a substantial reduction in disease activity in people with relapsing ...

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Real-World Data of First 12-Months of Ofatumumab ... Results: After the first 12 months of OFA treatment, relapses occurred in 12.0% of patients; new or enlarging T2-w lesions were observed in 12.7%; GELs in 3.5%; ...

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Study Details | NCT04926818 | Efficacy and Safety of ... A 2-year randomized, 3-arm, double-blind, non-inferiority study comparing the efficacy and safety of ofatumumab and siponimod versus fingolimod in pediatric ...

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Real-world pharmacovigilance of ofatumumab in multiple ... In the ALITHIOS open-label extension study, long-term safety data for ofatumumab indicated that 24.7% of patients experienced mild to moderate ...