Inebilizumab for Neuromyelitis Optica

(N-MOmentum LT Trial)

Recruiting at 21 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Amgen

Must be taking: Inebilizumab

Must not be taking: Rituximab, B-cell depleting agents

Disqualifiers: Severe infection, Tuberculosis, PML, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 42 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand the effects of long-term treatment with inebilizumab on circulating levels of immunoglobulins, B-cell counts, and other safety measures, and to further monitor repletion of immunoglobins and B-cell counts in participants with NMOSD who discontinue treatment. The objectives include: 1. To establish the nadir in circulating immunoglobulins (Ig) during chronic treatment with inebilizumab and ascertain the time needed to ensure restoration of pre-treatment baseline serum levels of IgG and IgM after discontinuation of treatment 2. To characterize B-cell counts throughout treatment with inebilizumab and after discontinuation until repletion of Immunoglobulin (Ig levels) 3. To assess long-term safety of inebilizumab 4. To assess other long-term effects of inebilizumab

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is inebilizumab safe for humans?

Inebilizumab, also known as Uplizna, has been generally well tolerated in clinical trials for neuromyelitis optica spectrum disorder (NMOSD), with common side effects including urinary tract infections and joint pain. It has been used safely in humans for over four years in studies, with the most frequent side effects being infusion reactions and respiratory infections. ^{1 2 3 4 5}

How does the drug inebilizumab work for neuromyelitis optica?

Inebilizumab is unique because it targets and depletes B cells that express a specific marker called CD19, which helps reduce attacks in neuromyelitis optica. It is given as an intravenous infusion and has been shown to lower the risk of attacks and hospitalizations in patients with this condition. ^{1 2 4 6 7}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults over 18 with Neuromyelitis Optica Spectrum Disorders who have been treated with inebilizumab for at least two years or are starting treatment. Participants must use effective contraception and give informed consent.

Inclusion Criteria

I am over 18 and can sign the consent form.

I am using, and will continue to use, effective birth control for 6 months after treatment.

I have been part of the N-MOmentum study for 2 years or am starting inebilizumab treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive long-term treatment with inebilizumab to monitor safety and effects on immunoglobulins and B-cell counts

42 months

Regular visits for blood sample collection and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation, focusing on repletion of immunoglobulins and B-cell counts

6 months

Treatment Details

Interventions

• Inebilizumab

Trial Overview The study tests the long-term safety of inebilizumab, monitoring its effects on immune system components like B-cells and immunoglobulins during and after treatment in NMOSD patients.

Participant Groups

Group I: Participants with NMOSD exposed to inebilizumab Experimental Treatment 2 Interventions

Participants with NMOSD who previously enrolled in N-MOmentum study, who participated for at least 2 years in the open label phase (OLP) of the study, and participants newly initiating inebilizumab treatment will have hematology, chemistry, B-cell count, serum immunoglobulin (Ig) levels, adverse events, concomitant medications list, NMOSD attacks information, antidrug antibody (ADA) status and titers collected.

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

Approved in United States as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Approved in European Union as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Approved in Canada as Uplizna for:

• Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Horizon Therapeutics Ireland DAC

Lead Sponsor

Trials

21

Recruited

2,500+

Findings from Research

Inebilizumab-cdon (Uplizna™) is an FDA-approved treatment for neuromyelitis optica spectrum disorder (NMOSD), demonstrating a safe and effective profile in clinical trials.

The drug works by depleting CD19+ B cells through mechanisms like antibody-dependent cell cytotoxicity (ADCC) and phagocytosis, which are crucial for its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis Optica Spectrum Disorder). Ali, F., Sharma, K., Anjum, V., et al.[2022]

Inebilizumab is an effective monoclonal antibody treatment for adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for anti-aquaporin-4 antibodies, significantly reducing the risk of NMOSD attacks and disability worsening over a period of at least 4 years.

The treatment was generally well tolerated, with common side effects including urinary tract infections and joint pain, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder. Nie, T., Blair, HA.[2023]

Inebilizumab, a monoclonal antibody that targets CD19 on B cells, has been approved for treating aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders (NMOSD) and has shown significant efficacy in prolonging the time to relapse in patients compared to placebo in the N-MOmentum study.

The treatment involves initial intravenous doses of 300 mg every 2 weeks, followed by maintenance infusions every 6 months, with common side effects including infusion reactions and infections, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inebilizumab in AQP4-Ab-positive neuromyelitis optica spectrum disorder. Siebert, N., Duchow, A., Paul, F., et al.[2021]

Inebilizumab is a humanized anti-CD19 monoclonal antibody that effectively targets and depletes CD19-expressing B cells, which is crucial for treating autoimmune diseases.

In June 2020, inebilizumab received its first approval in the USA for treating neuromyelitis optica spectrum disorder (NMOSD) in adults who are positive for AQP4-IgG, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inebilizumab: First Approval. Frampton, JE.[2021]

In a long-term study of 75 adults with neuromyelitis optica spectrum disorder treated with inebilizumab for over 4 years, the annualized attack rate was very low at 0.052 attacks per person per year, indicating strong efficacy in preventing attacks.

Inebilizumab was well tolerated with only 2.7% of participants experiencing serious adverse events, and no deaths reported, suggesting it is a safe treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. Rensel, M., Zabeti, A., Mealy, MA., et al.[2022]

Inebilizumab effectively depletes B cells in patients with neuromyelitis optica spectrum disorders (NMOSD) with a 300 mg intravenous dose administered on Day 1 and Day 15, followed by every 6 months, demonstrating its mechanism of action against this B cell-driven disease.

The study found that variations in drug exposure levels among patients did not significantly impact clinical outcomes, such as the risk of NMOSD attacks or disability progression, indicating consistent efficacy across different patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic modelling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders. Yan, L., Wang, B., She, D., et al.[2022]

Inebilizumab effectively induces rapid and durable depletion of B cells in adults with neuromyelitis optica spectrum disorder (NMOSD), showing significant clinical benefits over a follow-up period of at least 2.5 years.

Patients who achieved deeper B-cell depletion after the first 6 months of treatment experienced lower annual attack rates and fewer new MRI lesions, indicating that the extent of B-cell depletion is linked to improved disease stability and reduced activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. Bennett, JL., Aktas, O., Rees, WA., et al.[2022]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis Optica Spectrum Disorder). [2022]

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

Inebilizumab: A Review in Neuromyelitis Optica Spectrum Disorder. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Inebilizumab in AQP4-Ab-positive neuromyelitis optica spectrum disorder. [2021]

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

Inebilizumab: First Approval. [2021]

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

Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. [2022]

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

Pharmacodynamic modelling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. [2022]