Ofatumumab for Multiple Sclerosis

(SOSTOS Trial)

Recruiting at 86 trial locations

Overseen By Ahmed Obeidat

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: DMTs for RRMS

Must not be taking: Experimental MS drugs

Disqualifiers: Progressive MS, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 15 months

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether switching to ofatumumab, a treatment for multiple sclerosis (MS), benefits those with relapsing-remitting MS who haven't experienced a flare-up in the past year. Researchers aim to determine if a specific blood marker, serum neurofilament light, can predict who will benefit most from this switch. Participants will either switch to ofatumumab or continue their current treatment. This trial may suit individuals who have been on a disease-modifying treatment for at least six months, haven't had an MS relapse in the past six months, and can attend study visits for MRIs. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should be on a current disease-modifying therapy (DMT) for at least 6 months before joining. It seems like you may continue your current treatment while participating.

What is the safety track record for these treatments?

Studies have shown that ofatumumab is generally well-tolerated in people with multiple sclerosis (MS). This treatment targets specific cells in the immune system. Research indicates that most side effects are mild to moderate, such as headaches, injection site reactions, and upper respiratory infections. More serious risks are rare but can include infections due to a lowered immune response.

Real-world data supports these findings. A long-term study found that using ofatumumab continuously for up to 7 years was generally safe. The same study noted that while some people experienced side effects, these did not increase over time.

Overall, ofatumumab appears safe for many people, but like any treatment, it has potential risks. Always consult a healthcare provider to understand how it might affect you personally. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike many traditional treatments for multiple sclerosis (MS) that are administered intravenously or orally, Ofatumumab is unique because it's delivered via a simple subcutaneous injection. It targets CD20-positive B cells, a different mechanism compared to many MS drugs that primarily focus on T cells. Researchers are excited about Ofatumumab because this targeted approach might offer more precise control of the disease with potentially fewer side effects.

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

Research has shown that ofatumumab, which participants in this trial may receive, works well for treating relapsing multiple sclerosis (MS). Studies found that over 80% of patients using ofatumumab did not experience worsening disability over six months. Additionally, patients on this treatment had fewer relapses each year. Ofatumumab effectively reduced disease activity, as seen in MRI scans. Overall, it appears to help stabilize the disease and prevent further relapses in many patients. Another group in this trial will continue their current disease-modifying treatment (DMT) as prescribed by their physician. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-45 with relapsing-remitting multiple sclerosis (RRMS) who haven't had a relapse in the past year and have been on a disease-modifying treatment for at least six months. Participants should be able to attend study visits, use a wearable device, provide blood samples, and have an EDSS score of 0-5.5. Those with other diseases mimicking MS symptoms or active infections like COVID-19 cannot join.

Inclusion Criteria

Able to provide blood sample

I have been on a disease-modifying therapy for my RRMS for at least 6 months.

I have not had a cancer relapse in the last 6 months.

Exclusion Criteria

My symptoms or MRI results are not caused by multiple sclerosis.

Known sensitivity to gadolinium

My brain or spinal cord issues are caused by another condition, not my current illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Run-in

Participants undergo a six-month run-in period during which lab samples are collected

6 months

Regular visits for lab sample collection

Treatment

Participants are randomized to receive either ofatumumab or continue their current therapy for 15 months

15 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Disease modifying treatment (DMT)
• Ofatumumab

Trial Overview The study tests if switching to Ofatumumab is beneficial for RRMS patients showing no recent relapses but elevated neurofilament light levels compared to staying on their current therapy. It explores whether this biomarker predicts better outcomes with Ofatumumab.

How Is the Trial Designed?

Group I: Ofatumumab Experimental Treatment 1 Intervention

20 mg

Group II: DMT continued therapy Active Control 1 Intervention

Participants randomized to the continued therapy arm will continue to take their disease modifying treatment (DMT) as prescribed commercially by their physician.

Disease modifying treatment (DMT) is already approved in United States, European Union for the following indications:

Approved in United States as Arzerra for:

• Chronic lymphocytic leukemia (CLL) refractory to alemtuzumab and fludarabine
• In combination with chlorambucil for previously untreated CLL
• Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL
• In combination with fludarabine and cyclophosphamide for relapsed CLL

Approved in United States as Kesimpta for:

• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS

Approved in European Union as Arzerra/Kesimpta for:

• Chronic lymphocytic leukemia (CLL)
• Relapsing forms of multiple sclerosis (MS)

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

A total of 13,880 adverse drug reaction (ADR) reports related to multiple sclerosis (MS) treatments were analyzed from 2002 to 2020, revealing that most ADRs were not serious and predominantly affected females aged 18-65.

Unexpected ADRs were identified for several drugs, including dyslipidemia with fingolimod and natalizumab, and breast cancer with dimethyl fumarate, highlighting the need for ongoing pharmacovigilance to ensure the safety of new MS therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. Barbieri, MA., Sorbara, EE., Battaglia, A., et al.[2022]

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, an anti-CD20 monoclonal antibody approved for relapsing multiple sclerosis, was prescribed to 2,101 patients in a study that highlighted its increasing use as a first-line disease-modifying therapy, particularly among DMT-naïve patients, who made up a growing percentage of users over time.

The study found that the majority of patients were middle-aged women with mild MS symptoms, and many patients aged 55 and older were also treated with ofatumumab, suggesting a growing confidence in its safety and effectiveness beyond the initial trial population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic. Coyle, PK., Gorritz, M., Wade, RL., 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]

In a study analyzing 240,993 reports of disease-modifying therapies (DMTs) for multiple sclerosis (MS), four medications—natalizumab, interferon-β, dimethyl fumarate, and fingolimod—were found to have a significantly higher risk of cancer reporting, indicating a need for careful monitoring in patients using these treatments.

The study highlighted specific cancer types associated with these DMTs, such as upper aerodigestive tract and breast cancers linked to natalizumab and interferon-β, suggesting that regular cancer screenings may be necessary for younger patients on these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Disease-Modifying Therapies Prescribed to Persons with Multiple Sclerosis and Cancer: a WHO Pharmacovigilance Database Analysis. Dolladille, C., Chrétien, B., Peyro-Saint-Paul, L., et al.[2023]

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]

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]

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]

Citations

1. 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 ...

2. 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 ...

3. novartis.com novartis.com/us-en/news/media-releases/new-novartis-data-further-support-benefits-kesimpta-relapsing-ms-following-switch-from-oral-disease-modifying-therapies

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 ...

4. 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 ...

5. practicalneurology.com practicalneurology.com/news/kesimpta-shows-sustained-long-term-efficacy-and-safety-in-relapsing-multiple-sclerosis/2483559/

Kesimpta Shows Sustained Long-Term Efficacy and Safety in ... Across both studies, Kesimpta demonstrated high rates of no evidence of disease activity (NEDA-3), sustained suppression of MRI activity, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39917326/

Real-world pharmacovigilance of ofatumumab in multiple ... This real-world analysis of ofatumumab provides important safety insights, confirming known adverse reactions and identifying additional potential risks.

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

Real-world pharmacovigilance of ofatumumab in multiple ... By leveraging real-world data from the FAERS database, this work could identify differences in safety signals that may inform clinical decision- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798770/

The real-world safety of Ofatumumab - PubMed Central - NIH This study compiled a dataset derived from the FAERS database, which included real-world safety data on Ofatumumab from Q4 2009 to Q2 2024.