What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis similar to Ofatumumab (B cell depletion) and Siponimod (lymphocyte sequestration) include Ocrelizumab and Fingolimod. Ocrelizumab, like Ofatumumab, depletes B cells and can cause infusion reactions, infections, and a potential increased risk of malignancies. Fingolimod, similar to Siponimod, sequesters lymphocytes and is associated with side effects such as headache, elevated liver enzymes, bradyarrhythmia, macular edema, and increased risk of infections including varicella-zoster virus and cryptococcal infections. Both treatments require careful monitoring for adverse effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Sclerosis that are similar to Ofatumumab and Siponimod. Ofatumumab, a B-cell depleting therapy, is akin to Ocrelizumab and Rituximab, which also target CD20 on B cells to reduce their numbers and activity. Siponimod, which sequesters lymphocytes, is similar to Fingolimod, a sphingosine 1-phosphate receptor modulator that prevents lymphocytes from exiting lymph nodes, thereby reducing their presence in the central nervous system. These therapies aim to modulate the immune system to prevent MS relapses and progression.

What other types of research exist?

Promising novel alternatives to Ofatumumab and Siponimod for Multiple Sclerosis patients include Ocrelizumab (another anti-CD20 monoclonal antibody), Alemtuzumab (a monoclonal antibody targeting CD52), and Cladribine (an oral immunosuppressive drug). These therapies have shown efficacy in reducing relapse rates and disability progression in clinical trials. Additionally, newer therapies like Ublituximab (an anti-CD20 monoclonal antibody) and BTK inhibitors (e.g., Evobrutinib) are in late-stage clinical trials and may offer new options for MS treatment in the near future.

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Sphingosine-1-Phosphate Receptor Modulator

Ofatumumab + Siponimod vs Fingolimod for Pediatric Multiple Sclerosis (NEOS Trial)

Q: What is the mechanism of action of this treatment?

Multiple Sclerosis (MS) treatments often target the immune system to reduce disease activity and progression. Ofatumumab, a B cell depleting agent, works by targeting CD20 on B cells, leading to their destruction and reducing the inflammatory response that damages myelin. Siponimod, which sequesters lymphocytes, binds to sphingosine-1-phosphate receptors, preventing lymphocytes from exiting lymph nodes and thus reducing their presence in the central nervous system. These mechanisms are crucial for MS patients as they help to control the immune-mediated damage to the nervous system, potentially reducing relapses and slowing disease progression. Other common treatments include interferon beta, which modulates immune response, and glatiramer acetate, which mimics myelin proteins to divert immune attacks away from actual myelin.

Phase 3

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior or evidence of one or more new T2 lesions within 12 months

Between 10 to <18 years of age at randomization

Must not have

Participants with severe renal insufficiency

Participants with progressive MS

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-dose month 3, 5 and month 12

Awards & highlights

Summary

This trial tests three medications in children and teens with multiple sclerosis to find effective treatments. The drugs work by reducing harmful immune cells or preventing them from attacking the nervous system.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at injection sites, infections due to weakened immune response, liver issues, high blood pressure, breathing difficulties, and potential heart problems. Each drug has its own profile of possible side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am between 10 and 17 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe kidney problems.

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My MS is getting worse.

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I have a chronic immune system disease other than MS.

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I do not have severe heart disease or alarming ECG results.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-dose month 3, 5 and month 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-dose month 3, 5 and month 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-dose month 3, 5 and month 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Annualized relapse rate (ARR) in target pediatric participants

Secondary study objectives

Annualized T2 lesion rate

Annualized relapse rate (ARR) as compared to historical interferon β-1a data

Neurofilament light chain (NfL) concentrations

+5 more

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: siponimod - 0.5 mg, 1 mg or 2 mg/ placeboExperimental Treatment2 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/ placeboExperimental Treatment2 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/ placeboActive Control2 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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ofatumumab

2013

Completed Phase 3

~1480

Siponimod

2019

Completed Phase 3

~190

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Sclerosis (MS) treatments often target the immune system to reduce disease activity and progression. Ofatumumab, a B cell depleting agent, works by targeting CD20 on B cells, leading to their destruction and reducing the inflammatory response that damages myelin. Siponimod, which sequesters lymphocytes, binds to sphingosine-1-phosphate receptors, preventing lymphocytes from exiting lymph nodes and thus reducing their presence in the central nervous system. These mechanisms are crucial for MS patients as they help to control the immune-mediated damage to the nervous system, potentially reducing relapses and slowing disease progression. Other common treatments include interferon beta, which modulates immune response, and glatiramer acetate, which mimics myelin proteins to divert immune attacks away from actual myelin.

Construction of miRNA-regulated drug-pathway network to screen drug repurposing candidates for multiple sclerosis.Disease-modifying treatments for progressive multiple sclerosis.