Ofatumumab for Early Relapsing-Remitting Multiple Sclerosis

(AGNOS Trial)

Not currently recruiting at 84 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must not be taking: Experimental drugs, Chemotherapy

Disqualifiers: Neuromyelitis optica, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ofatumumab, a medication, to assess its effects on individuals with early-stage Relapsing-Remitting Multiple Sclerosis (RRMS), a type of MS characterized by symptom flare-ups followed by improvement. The researchers aim to understand the drug's impact through clinical check-ups, MRIs, and other tests, comparing results with healthy individuals. Participants with a recent RRMS diagnosis who have not yet received MS-specific treatments are ideal candidates. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial requires that participants have not used any Disease Modifying Therapy (DMT) or chemotherapeutic medications for MS before joining. If you are currently on these medications, you would need to stop them to participate.

What is the safety track record for ofatumumab?

Previous studies have shown that ofatumumab is well-tolerated by patients with relapsing-remitting multiple sclerosis (RRMS). Research indicates no unexpected safety issues with doses up to 700 mg. Reports also suggest that ofatumumab is safe in real-world settings and has a safety profile similar to teriflunomide. Overall, existing data suggest that ofatumumab appears safe for people with RRMS. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Ofatumumab is unique because it targets CD20, a protein found on the surface of B cells, which are part of the immune system and play a role in multiple sclerosis (MS) progression. Unlike many existing treatments for relapsing-remitting multiple sclerosis, which often require intravenous administration, ofatumumab is delivered subcutaneously using an autoinjector, making it potentially more convenient for patients. Researchers are excited about ofatumumab because it offers a targeted approach that may reduce relapses and slow disease progression while providing a more manageable treatment routine.

What is the effectiveness track record for ofatumumab in treating early relapsing-remitting multiple sclerosis?

Research shows that ofatumumab, which participants in this trial may receive, effectively treats relapsing-remitting multiple sclerosis (RRMS). Studies have found that it greatly reduces disease activity in people with RRMS. One study showed that ofatumumab was more effective than teriflunomide at reducing relapses and slowing disease progression. This treatment targets and reduces certain immune cells (B cells) involved in the disease. These findings suggest that ofatumumab can help stabilize RRMS early in its course. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for young adults aged 18-35 with very early Relapsing Remitting Multiple Sclerosis (RRMS), diagnosed within the last 6 months and who haven't started any MS treatments. Participants must be able to use a wearable device, provide blood samples, and undergo MRI scans. Pregnant women, those with other immune diseases or infections, previous MS treatments, or severe kidney issues can't join.

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study

I have not received any MS disease-modifying treatments before.

I have been diagnosed with relapsing-remitting MS according to the McDonald Criteria.

Exclusion Criteria

I am allergic to some medications or their ingredients used in this study.

I am using experimental drugs for my multiple sclerosis.

My MS symptoms are not caused by another disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive 20 mg ofatumumab subcutaneously monthly for 18 months

18 months

Regular clinical visits with assessments and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Optional extension phase for long-term clinical and MRI outcomes

What Are the Treatments Tested in This Trial?

Interventions

• Ofatumumab

Trial Overview The study tests Ofatumumab's effects on new RRMS patients by comparing clinical outcomes and MRI results before and after treatment. It also uses digital monitoring and biomarker analysis to track changes in disease progression against healthy controls without MS.

How Is the Trial Designed?

Group I: Ofatumumab Experimental Treatment 1 Intervention

Ofatumumab will be provided in an autoinjector for subcutaneous administration. Dosing regimen for this study is an initial dose of 20mg at Baseline/Week 0, followed by Week 1, 2 and every month thereafter, beginning at Week 4 (Month 1) until Month 18. There will be an optional extension of dosing through month 30.

Group II: Healthy Control Active Control 1 Intervention

Healthy Control arm will be age- and sex-matched subjects (to the ofatumumab treated arm) and will not receive a study treatment.

Ofatumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Kesimpta for:

• Relapsing forms of multiple sclerosis (MS)
• Clinically isolated syndrome
• Relapsing-remitting multiple sclerosis
• Active secondary progressive multiple sclerosis

Approved in United States as Kesimpta for:

• Relapsing forms of multiple sclerosis (MS)
• Clinically isolated syndrome
• Relapsing-remitting multiple sclerosis
• Active secondary progressive multiple sclerosis

Approved in United States as Arzerra for:

• Certain types of chronic lymphocytic leukemia (CLL)

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 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 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 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, a monoclonal antibody for treating relapsing forms of multiple sclerosis, effectively depletes B cells at a 20-mg subcutaneous dose, achieving a target B cell count of 8 cells/µL within 11 days with minimal repletion between doses.

The pharmacokinetics of ofatumumab were analyzed using data from 1486 patients, showing that only body weight affected drug levels, but this did not necessitate any dose adjustments based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic-B Cell Modeling for Ofatumumab in Patients with Relapsing Multiple Sclerosis. Yu, H., Graham, G., David, OJ., 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, 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 (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 ... Ofatumumab demonstrated superior efficacy and similar safety versus teriflunomide in ASCLEPIOS I/II in people with relapsing multiple ...

2. 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 ...

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

Real-world effectiveness and safety of ofatumumab in ... Ofatumumab (OFA), a fully human anti-CD20 monoclonal antibody, has shown promising efficacy in treating relapsing multiple sclerosis (RMS) ...

4. archivesofmedicalscience.com archivesofmedicalscience.com/Early-treatment-with-ofatumumab-increases-the-likelihood-of-stabilizing-disease-in,205112,0,2.html

Early treatment with ofatumumab increases the likelihood ... Early treatment with ofatumumab increases the likelihood of stabilizing disease in patients with relapsing-remitting multiple sclerosis. Adam Stepień 1.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10444716/

The Development of Ofatumumab, a Fully Human Anti-CD20 ... Ofatumumab is the first fully human anti-CD20 monoclonal antibody to be approved for the treatment of relapsing multiple sclerosis. Rapid and sustained near- ...

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000000125

Safety and efficacy of ofatumumab in relapsing-remitting ... Ofatumumab (up to 700 mg) given 2 weeks apart was not associated with any unexpected safety concerns and was well tolerated in patients with RRMS.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12472045/

Real-World Data of First 12-Months of Ofatumumab Treatment ... Real-world data confirmed the high efficacy and favorable safety profile of OFA in patients with relapsing-remitting multiple sclerosis (RRMS).

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01457924

Study Details | NCT01457924 | Ofatumumab ... Ofatumumab has been shown to be both well tolerated and efficacious in several indications, including a small, placebo-controlled trial in RRMS using an ...