Inebilizumab for Neuromyelitis Optica

Recruiting at 29 trial locations

Overseen By Horizon Therapeutics

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must not be taking: Alemtuzumab, Rituximab, IVIG, others

Disqualifiers: Hepatitis, HIV, Cancer, TB, 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: 13

Duration: 28 weeks

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as rituximab, IVIG, and others listed in the exclusion criteria. If you're on any of these, you may need to stop them for a specific period before joining the trial.

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 3 4 6 7}

What is the purpose of this trial?

A Phase 2, open-label, multicenter study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inebilizumab in eligible pediatric participants 2 to \< 18 years of age with recently active neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for autoantibodies against aquaporin-4 (AQP4-immunoglobulin \[Ig\]G).

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for kids aged 2 to <18 with Neuromyelitis Optica Spectrum Disorder (NMOSD) who've had at least one relapse in the past year or two in the last two years. They must test positive for AQP4-IgG antibodies and meet specific diagnostic criteria. Kids can't join if they've recently taken certain meds, received live vaccines or blood transfusions, have uncontrolled autoimmune diseases, significant organ dysfunction, severe allergies to multiple drugs/foods, or low B-cell counts.

Inclusion Criteria

I have NMOSD and tested positive for anti-AQP4-IgG.

I am between 2 and 17 years old.

I have had at least one NMOSD flare-up in the past year or two in the last two years.

Exclusion Criteria

Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to Day 1

Any condition that, in the opinion of the Investigator, would interfere with the evaluation or administration of the Investigational Product or interpretation of subject safety or study results

Receipt of any of the following within 2 months prior to Day 1: Cyclosporine, Methotrexate, Mitoxantrone, Cyclophosphamide, Tocilizumab, Satralizumab, Eculizumab, Receipt of natalizumab (Tysabri®) within 6 months prior to Day 1, Severe drug allergic history or anaphylaxis to 2 or more food products or medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid), Diagnosed with a concurrent autoimmune disease that is uncontrolled (unless approved by the medical monitor), Recent receipt of live/attenuated vaccine or blood transfusion

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive Inebilizumab administered intravenously over 28 weeks

28 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

4 visits (in-person)

Treatment Details

Interventions

• Inebilizumab

Trial Overview The study tests Inebilizumab's effects on children with NMOSD. It's an open-label Phase 2 trial where all participants receive the drug; researchers will look at how it moves through and affects the body (PK/PD), as well as its safety profile.

Participant Groups

Group I: Inebilizumab Experimental Treatment 1 Intervention

Infusion of Inebilizumab

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 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-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 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]

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]

References

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

Inebilizumab: First Approval. [2021]

2. 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]

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

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

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

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

5. Spain pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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