Ofatumumab for Multiple Sclerosis

(SOSTOS Trial)

Recruiting at 80 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 will test if patients with a specific type of multiple sclerosis benefit from switching to a new medication. The medication aims to reduce harmful cells in the nervous system, potentially preventing future issues. It has been approved in several countries for treating this condition.

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.

Is Ofatumumab safe for humans?

Ofatumumab, used for treating multiple sclerosis, generally has a manageable safety profile. Common side effects include colds, headaches, and infections, but these are usually manageable. There is no strong link between Ofatumumab and serious infections over long-term use. ^{1 2 3 4 5}

How is the drug Ofatumumab unique in treating multiple sclerosis?

Ofatumumab is unique because it is a fully human anti-CD20 monoclonal antibody that can be self-administered by patients through subcutaneous injection, offering a convenient option for treating relapsing forms of multiple sclerosis. It has been shown to be more effective than some oral treatments in reducing relapse rates and MRI-detected lesions, with a generally manageable side effect profile. ^{1 4 6 7 8}

What data supports the effectiveness of the drug Ofatumumab for treating multiple sclerosis?

Ofatumumab has been shown to be more effective than teriflunomide in reducing relapse rates and MRI-detected lesions in people with relapsing multiple sclerosis, with a generally manageable safety profile. ^{1 4 6 7 9}

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

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, 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, 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 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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic. [2023]

3. 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]

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

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

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

Association Between Disease-Modifying Therapies Prescribed to Persons with Multiple Sclerosis and Cancer: a WHO Pharmacovigilance Database Analysis. [2023]

7. Germany 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]. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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