Ofatumumab for Multiple Sclerosis

(FILIOS Trial)

Recruiting at 24 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

Trial Summary

What is the purpose of this trial?

This study will evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of a new dosage of ofatumumab compared to the approved dosage of ofatumumab followed by extended treatment in participants with relapsing multiple sclerosis.

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.

What data supports the effectiveness of the drug Ofatumumab for Multiple Sclerosis?

Research shows that Ofatumumab is effective for treating relapsing multiple sclerosis, with better clinical outcomes and MRI results compared to another drug, teriflunomide, in trials. It has been approved for use in Canada and has shown superior efficacy and safety over a period of up to 2.5 years. ^{1 2 3 4 5}

Is ofatumumab safe for humans?

Ofatumumab has been studied for up to 3.5 years in people with multiple sclerosis, showing a favorable safety profile with good tolerability and low risk of immune reactions. ^{1 2 3 6 7}

How is the drug Ofatumumab unique for treating multiple sclerosis?

Ofatumumab is unique because it is a fully human anti-CD20 monoclonal antibody that can be self-administered as a subcutaneous injection, offering convenience compared to other treatments that require intravenous administration. It effectively reduces relapse rates and disability progression in relapsing forms of multiple sclerosis, with a generally manageable side effect profile. ^{1 3 8 9 10}

Eligibility Criteria

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 am between 18 and 60 years old.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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 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 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 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 (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, 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous ofatumumab treatment of multiple sclerosis and related disorders: An observational study. [2022]

2. England 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of four-year ofatumumab treatment in relapsing multiple sclerosis: The ALITHIOS open-label extension. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis. [2023]

7. Spain pubmed.ncbi.nlm.nih.gov

Ofatumumab for relapsing forms of multiple sclerosis. [2022]

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

Ofatumumab: A Review in Relapsing Forms of Multiple Sclerosis. [2022]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Ofatumumab - a new drug for the treatment of multiple sclerosis]. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study. [2022]