Ofatumumab for Multiple Sclerosis

(ELIOS Trial)

Recruiting at 2 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Ofatumumab

Must not be taking: Cladribine, Alemtuzumab, Anti-CD20

Disqualifiers: Primary progressive MS, Pregnancy, 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

Compensation: Varies

Number of Visits: 5

Duration: 24 months

224 Participants Needed

Trial Summary

What is the purpose of this trial?

The exploratory ELIOS study aims to assess the value of novel investigational Eye Movement Biomarkers (EMBs) in tracking disease-related changes among a real-world cohort of Canadian patients with active RRMS, within the context of disease-modifying treatment (i.e., ofatumumab). To that end, the study will use the patented investigational, Eye Tracking Neurological Assessment (ETNA-ProgMS) SaMD (v1.0.11 or later), which has not yet received Health Canada approval, to reliably and accurately track eye movements with precision.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using other investigational drugs, you must stop them at least 30 days before the trial or longer if needed. Also, you cannot have been treated with certain medications like cladribine or alemtuzumab in the past 12 months.

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

Ofatumumab is effective in treating relapsing forms of multiple sclerosis (MS) by reducing the frequency of relapses and the risk of disability progression, as shown in phase III trials where it outperformed teriflunomide. It is also approved in several countries for this use and has a generally manageable side effect profile. ^{1 2 3 4 5}

Is ofatumumab safe for humans?

Ofatumumab, used for treating multiple sclerosis, has been studied for safety over long-term use. Common side effects include mild infections like colds and headaches, which are generally manageable. Serious infections were not linked to changes in immune system markers after 3.5 years of treatment. ^{1 2 5 6 7}

How does the drug Ofatumumab differ from other treatments for multiple sclerosis?

Ofatumumab is unique because it is a monoclonal antibody that targets CD20, a protein on the surface of B cells, which are part of the immune system. This mechanism helps reduce inflammation and nerve damage in multiple sclerosis, and it is administered as an injection under the skin, offering a different route compared to some other treatments that may require intravenous administration. ^{8 9 10 11 12}

Research Team

Study Director

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for Canadian patients with active Relapsing-Remitting Multiple Sclerosis (RRMS). Participants should be currently undergoing treatment with ofatumumab. The study excludes individuals who do not meet the specific criteria set by the researchers, which are not detailed here.

Inclusion Criteria

I understand and speak Canadian English or French.

I have been diagnosed with active relapsing-remitting MS.

Patients who can provide blood samples

Exclusion Criteria

I have a chronic immune system disease other than MS, treated with immune therapy.

Patients using other investigational drugs within 30 days prior to or at the Baseline Visit, or within a period corresponding to five elimination half-lives, whichever is longer, or using other investigational drugs for which the expected pharmacodynamic effect has not returned to baseline

Contraindication or inability to undergo regular testing (e.g., MRI, blood tests) as per standard of care

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ofatumumab and have their eye movements tracked using ETNATM-ProgMS SaMD at baseline, 3-, 6-, 12-, and 24-months

24 months

5 visits (in-person) at baseline, 3, 6, 12, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• ETNATM-ProgMS

Trial Overview The ELIOS study is testing a new software called ETNA-ProgMS that tracks eye movements to monitor disease changes in RRMS patients. This investigational tool aims to provide precise measurements and has yet to be approved by Health Canada.

Participant Groups

Group I: ETNATM-ProgMS Experimental Treatment 1 Intervention

Patients with active RRMS being prescribed ofatumumab as part of routine clinical care will have their eye movements reliably and accurately tracked using ETNATM-ProgMS SaMD (v1.0.11 or later) at baseline, 3-, 6-, 12-, and 24-months following ofatumumab initiation

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 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 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 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, 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]

Ofatumumab, used for treating relapsing multiple sclerosis, was well tolerated in a study of 1969 patients over a median of 35.5 months, with no new safety risks identified and a low incidence of serious infections.

The treatment showed a favorable benefit-risk profile, as there were no cases of opportunistic infections or progressive multifocal leukoencephalopathy, and the risk of malignancies remained low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Hauser, SL., Cross, AH., Winthrop, K., et al.[2022]

Ofatumumab is well tolerated in patients with relapsing multiple sclerosis (RMS), with 24.7% experiencing mild to moderate injection-related reactions (IRRs) over up to 4 years of treatment, indicating a favorable safety profile.

The incidence and severity of IRRs were similar for patients continuously on ofatumumab and those switched from teriflunomide, and pre-medication did not significantly affect IRR outcomes, allowing for effective home management of RMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis. Kramer, J., Linker, R., Paling, D., et al.[2023]

AMG 160 is a bispecific T-cell engager that targets prostate-specific membrane antigen (PSMA) and CD3, showing promise in inducing T-cell activity against prostate cancer.

The preclinical data suggests that AMG 160 could enhance immune responses in prostate cancer treatment, highlighting its potential as a novel therapeutic approach in immune oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BiTE-ing into Prostate Cancer with Bispecific T-cell Engagers. Kamat, NV., Yu, EY., Lee, JK.[2021]

The abstract lists a variety of medical interventions, including targeted therapies and drugs, indicating a broad range of potential treatments for various conditions.

However, the abstract does not provide specific efficacy or safety data for these interventions, making it difficult to assess their effectiveness or mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayés, M., Rabasseda, X., Prous, JR.[2007]

The abstract lists a wide range of medical interventions, including various drugs and therapies, indicating a focus on diverse treatment options for different conditions.

However, the abstract does not provide specific findings related to safety, efficacy, or mechanisms of action for any of the listed interventions, making it difficult to extract key takeaways regarding their clinical impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. Bayes, M., Rabasseda, X., Prous, JR.[2007]

A 34-year-old man with recurrent glioblastoma was treated with 2 cycles of low-dose [177Lu]Lu-PSMA after other treatment options were exhausted, showing intense PSMA signal in the tumor, indicating potential effectiveness.

The case suggests that [177Lu]Lu-PSMA therapy could be a promising treatment avenue for glioblastoma, warranting further investigation into its efficacy and safety in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma. More, S., Naiker, T., Jacobs, N., et al.[2023]

Lutetium-177-PSMA-617 is the only approved PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer, showing promise based on the phase III VISION trial.

The use of PSMA-targeted therapies is expanding, with ongoing clinical trials exploring both monotherapy and combination treatments, indicating a rapidly evolving field that may improve patient outcomes in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of PSMA-targeted radioligand therapy in prostate cancer: current data and future trials. Jang, A., Kendi, AT., Sartor, O.[2023]

References

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

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

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

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

4. 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]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. [2022]

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

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis. [2023]

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

BiTE-ing into Prostate Cancer with Bispecific T-cell Engagers. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. [2007]

10. Spain pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. [2007]

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

Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Status of PSMA-targeted radioligand therapy in prostate cancer: current data and future trials. [2023]