Ofatumumab for Early Relapsing-Remitting Multiple Sclerosis

(AGNOS Trial)

Recruiting at 83 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

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the impact of ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) participants that are very early in the course of their disease using clinical and magnetic resonance imaging (MRI) outcomes. The study will also assess changes in disease using monitoring techniques including digital biometric device use, biomarker analysis and non-conventional MRI. Select outcomes in the ofatumumab treated group will be compared to a group of Healthy participants to determine if there are similarities between the groups after the patients with MS undergo treatment with ofatumumab.

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 data supports the effectiveness of the drug Ofatumumab for treating early relapsing-remitting multiple sclerosis?

Research shows that Ofatumumab is more effective than teriflunomide in reducing relapse rates and MRI-detected lesions in relapsing multiple sclerosis, with a generally manageable safety profile. ^{1 2 3 4 5}

How is the drug Ofatumumab different from other treatments for relapsing-remitting 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 and independence from hospital visits. It targets a different region on the CD20 receptor compared to other similar drugs, leading to efficient B-cell depletion and has shown to be more effective than some existing treatments like teriflunomide in reducing relapse rates and disability progression. ^{3 4 5 6 7}

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 (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 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, 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

Population Pharmacokinetic-B Cell Modeling for Ofatumumab in Patients with Relapsing Multiple Sclerosis. [2022]

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

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