Ofatumumab for Multiple Sclerosis

(FILIOS Trial)

Recruiting at 78 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: B cell therapies

Disqualifiers: PML, Hepatitis, Immunodeficiency, Malignancy, 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

Duration: 12 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new dosage of ofatumumab, a monoclonal antibody, for individuals with relapsing forms of multiple sclerosis (MS), a condition where the immune system attacks the protective covering of nerves. The study examines how this new dosage is processed in the body compared to the approved dosage. Participants will receive either the new dosage or the current approved dosage, and researchers will monitor safety and effectiveness. Those interested in joining should have a diagnosis of relapsing-remitting MS or active secondary progressive MS. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising treatment.

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

The trial requires that you stop taking certain medications, specifically B cell targeted therapies like ocrelizumab, rituximab, ofatumumab, ublituximab, and inebilizumab. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ofatumumab is generally safe. Studies found that over 80% of patients using ofatumumab for up to five years did not experience worsening disability. In everyday use, many patients did not have relapses, which are flare-ups of symptoms. Long-term data indicates that only about 24.7% of patients reported mild to moderate side effects. This suggests that ofatumumab is usually well-tolerated by people with multiple sclerosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Ofatumumab is unique because it offers a targeted approach for treating multiple sclerosis (MS). Unlike traditional MS treatments that often work by broadly suppressing the immune system, Ofatumumab specifically targets and depletes B-cells, which play a key role in the disease's progression. This targeted action aims to reduce relapses and slow down the disease with potentially fewer side effects. Researchers are excited about Ofatumumab because it can be administered via a convenient under-the-skin injection, allowing for more consistent dosing and possibly improving patient adherence compared to intravenous options.

What evidence suggests that this treatment might be an effective treatment for multiple sclerosis?

Research has shown that ofatumumab works well for treating multiple sclerosis (MS). Over five years, more than 80% of patients using ofatumumab did not experience worsening disability. Studies also found that patients had fewer MS flare-ups, reducing their relapse rates. After 12 months of treatment, only 12% of patients developed new or worsening brain lesions, which indicate MS activity. These findings suggest that ofatumumab can effectively help manage MS symptoms. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 60 with relapsing multiple sclerosis, including those with relapsing-remitting MS or active secondary progressive MS. Participants must understand the study and agree to join by signing a consent form.

Inclusion Criteria

I have signed the consent form to participate in the study.

I have been diagnosed with relapsing MS according to the 2017 criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the new or approved dosage of ofatumumab

12 weeks

Extended Treatment

Participants continue to receive extended treatment with ofatumumab

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ofatumumab

Trial Overview The study tests how the body processes and responds to two different doses of Ofatumumab—a new dose versus the already approved one—in people with relapsing multiple sclerosis over an extended period.

How Is the Trial Designed?

Group I: Ofatumumab dose 2 Experimental Treatment 1 Intervention

New dosage

Group II: Ofatumumab dose 1 Active Control 2 Interventions

Approved dosage

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

In a retrospective study of 50 patients treated with intravenous ofatumumab for multiple sclerosis and related disorders over a median duration of 2.2 years, the annualized relapse rate significantly decreased from 1.03 to 0.38, indicating effective disease control.

While ofatumumab treatment showed a stabilization of disability worsening (7% at 24 months), there was a high incidence of infusion-related reactions (86% during the first infusion), suggesting a need for careful monitoring during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. El Mahdaoui, S., Romme Christensen, J., Magyari, M., 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]

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 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, used for treating relapsing multiple sclerosis, was well tolerated in a study of 1969 patients over a median of 35.5 months, with no new safety risks identified and a low incidence of serious infections.

The treatment showed a favorable benefit-risk profile, as there were no cases of opportunistic infections or progressive multifocal leukoencephalopathy, and the risk of malignancies remained low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Hauser, SL., Cross, AH., Winthrop, K., et al.[2022]

Ofatumumab is well tolerated in patients with relapsing multiple sclerosis (RMS), with 24.7% experiencing mild to moderate injection-related reactions (IRRs) over up to 4 years of treatment, indicating a favorable safety profile.

The incidence and severity of IRRs were similar for patients continuously on ofatumumab and those switched from teriflunomide, and pre-medication did not significantly affect IRR outcomes, allowing for effective home management of RMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis. Kramer, J., Linker, R., Paling, D., et al.[2023]

Ofatumumab is a highly effective and cost-effective first-line treatment for relapsing-remitting multiple sclerosis (RRMS) in Canada, showing better outcomes and lower costs compared to other therapies like teriflunomide and interferons.

In terms of cost-effectiveness, ofatumumab demonstrated incremental cost-effectiveness ratios (ICERs) of $24,189 per quality-adjusted life-year (QALY) compared to glatiramer acetate, indicating a strong value for healthcare spending at a willingness-to-pay threshold of $50,000/QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada. Baharnoori, M., Bhan, V., Clift, F., et al.[2022]

Ofatumumab, administered subcutaneously via an autoinjector, is bioequivalent to the pre-filled syringe method, showing similar pharmacokinetic profiles in a study of 256 patients with relapsing multiple sclerosis.

Both administration methods resulted in rapid B-cell depletion, with counts dropping from a baseline of 214.0 cells/µL to 2.0 cells/µL by Day 14, and the treatment was well tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study. Bar-Or, A., Wiendl, H., Montalban, X., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40652442/

Five-Year Safety and Efficacy Outcomes with Ofatumumab ... With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12450139/

Five-Year Safety and Efficacy Outcomes with Ofatumumab ... With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925002028

Real-world effectiveness and safety of ofatumumab in ... Outcomes included annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS), and the percentage of patients free from relapse, MRI ...

4. mdpi.com mdpi.com/1648-9144/61/9/1568

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%; ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211034825003591

Real-world change in annualized relapse rate and ... MS-related outpatient visits were reduced by 30 % after OMB initiation. •. Benefits of OMB's efficacy in reducing relapses in MS translated to reduced HCRU.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000210474

Continuous Ofatumumab Treatment Up to 7 Years Shows a ... Previously reported data up to 6 years of ofatumumab treatment demonstrated a favorable safety profile and sustained efficacy.

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1521726/full

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 ...