Ofatumumab for Multiple Sclerosis

(KATHAROS Trial)

Recruiting at 12 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Ofatumumab

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Alcohol abuse, Immunodeficiency, 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: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate whether ofatumumab is excreted at quantifiable levels and at which concentrations in breast milk of lactating women with RMS). The study will include lactating mothers who plan to breastfeed and initiate/re-initiate ofatumumab 2-24 weeks post-partum.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants taking medications prohibited by the study protocol. It's best to discuss your current medications with the study team to see if they are allowed.

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

Research shows that Ofatumumab is effective in reducing relapse rates and MRI-detected lesions in patients with relapsing forms of multiple sclerosis, and it has a generally manageable safety profile. It was found to be more effective than another drug, teriflunomide, in clinical trials. ^{1 2 3 4 5}

What makes 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 and independence compared to intravenous treatments. It targets a different region on the CD20 receptor than other similar drugs, making it effective in reducing relapses and disability progression in multiple sclerosis. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for lactating women over 18 with relapsing forms of Multiple Sclerosis (RMS) who have given birth to a term infant and are exclusively breastfeeding. They must be planning to start or restart treatment with Ofatumumab between 2-24 weeks after giving birth, independent of the study.

Inclusion Criteria

I have signed the consent form for this study.

I am breastfeeding exclusively and agree to provide breast milk samples.

I have given birth to a full-term baby.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Sampling

Milk samples and a blood sample are collected from participants

up to 12 weeks

Weekly visits for sample collection

Safety Follow-up

Participants and their babies are monitored for health and safety

9 months

Treatment Details

Interventions

• Ofatumumab

Trial Overview The study tests if the drug Ofatumumab, used for treating RMS, can be found in breast milk and at what levels when taken by breastfeeding mothers postpartum.

Participant Groups

Group I: Ofatunumab Experimental Treatment 1 Intervention

Recommended dose as per ofatumumab label. Injection at weeks 0,1,2 and monthly starting at week 4.

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, 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]

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 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 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, 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]

References

1. 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]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

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