Empasiprubart vs IVIg for Multifocal Motor Neuropathy

(Empassion Trial)

Recruiting at 5 trial locations

Overseen By Sabine Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: argenx

Must be taking: IVIg

Disqualifiers: Autoimmune disease, Motor neuron disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to compare empasiprubart and IVIg in adult patients with MMN. The study consists of a double-blinded part A (empasiprubart, IVIg) and an open-label part B (empasiprubart). The maximum study duration for participants is up to 49 months.

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 requires that you continue your current IVIg treatment without changes for at least 8 weeks before screening.

Is IVIg safe for treating multifocal motor neuropathy?

IVIg is generally considered safe for treating multifocal motor neuropathy, with most side effects being mild and resolving by the end of the study period. Some serious adverse events were reported, but they were not related to the study drug. ^{1 2 3 4 5}

How does the drug Empasiprubart differ from IVIg in treating multifocal motor neuropathy?

Empasiprubart is being compared to IVIg, which is the current standard treatment for multifocal motor neuropathy. IVIg is administered intravenously and often requires repeated courses to maintain improvement, but its long-term efficacy is debated. Empasiprubart may offer a novel approach, potentially differing in administration, mechanism, or long-term effects, though specific details are not provided in the available research. ^{1 4 5 6 7}

Eligibility Criteria

Adults with a confirmed diagnosis of multifocal motor neuropathy (MMN) who have responded to IVIg treatment in the past five years. Participants must be at least 18, on a stable IVIg regimen for at least 8 weeks, and immunized against certain bacterial pathogens or willing to get immunized before starting the study.

Inclusion Criteria

I am receiving an IVIg dose of at least 0.125 g/kg weekly.

I am on IVIg treatment every 2-5 weeks, at a dose of 0.4 to 2.0 g/kg.

I have had a positive response to IVIg treatment in the last 5 years.

Exclusion Criteria

I have symptoms that may not be due to MMN, like muscle weakness or sensory issues.

I do not have autoimmune diseases or conditions that could risk my safety in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Double-blinded phase where participants receive either empasiprubart with IVIg-placebo or IVIg with empasiprubart-placebo

24 weeks

Treatment Part B

Open-label phase where participants receive empasiprubart

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empasiprubart
• IVIG

Trial Overview The trial is testing Empasiprubart versus IVIg in adults with MMN. It includes a double-blinded phase where participants don't know if they're getting Empasiprubart or IVIg, followed by an open-label phase where everyone receives Empasiprubart. The trial can last up to 49 months per participant.

Participant Groups

Group I: Part B - empasiprubart Experimental Treatment 1 Intervention

After completion of part A, participants can proceed to part B where they receive empasiprubart (no IVIg)

Group II: Part A - empasiprubart + IVIg-placebo Experimental Treatment 2 Interventions

During the double blinded - double dummy part A, participants receive empasiprubart and a placebo resembling the IVIg treatment in this arm

Group III: Part A - IVIg + empasiprubart-placebo Active Control 2 Interventions

During the double blinded - double dummy part A, participants receive IVIg and a placebo resembling the empasiprubart treatment in this arm

Who Is Running the Clinical Trial?

argenx

Lead Sponsor

Trials

76

Recruited

11,500+

Tim Van Hauwermeiren

argenx

Chief Executive Officer since 2008

B.Sc. and M.Sc. in Bioengineering from Ghent University, Executive MBA from The Vlerick School of Management

Dr. Peter Ulrichts

argenx

Chief Medical Officer since 2023

MD from Maastricht University, PhD in Molecular Immunology from Maastricht University

Findings from Research

In a study of 44 adults with multifocal motor neuropathy (MMN), intravenous immunoglobulin (IVIG) significantly improved muscle strength, with a 3.75% increase in grip strength during treatment compared to a 31.38% decline during placebo (p=0.005).

IVIG was found to be safe and well-tolerated, with only one serious adverse reaction reported and a majority of participants (69%) switching from placebo to open-label IVIG due to deterioration, indicating its effectiveness in managing MMN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy. Hahn, AF., Beydoun, SR., Lawson, V., et al.[2022]

In a phase 3 clinical trial involving 13 patients with multifocal motor neuropathy (MMN), maintenance treatment with intravenous immunoglobulin (IVIg) at a dose of 1.0 g/kg every 3 weeks for 52 weeks resulted in sustained improvements in muscle strength, as measured by the Medical Research Council (MRC) sum score and hand-grip strength.

The treatment was found to be safe, with only mild adverse effects reported, and serious adverse events were not deemed related to the IVIg therapy, indicating that IVIg is an effective and well-tolerated option for managing MMN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial. Kuwabara, S., Misawa, S., Mori, M., et al.[2021]

A retrospective study of 40 patients with multifocal motor neuropathy (MMN) showed that high-dose intravenous immunoglobulin (IVIg) treatment led to significant short-term improvements in muscle strength, with 70% of treatment-naive patients showing improvement compared to only 20% in a historical placebo group.

However, long-term outcomes were less favorable, as only 22% of patients remained in remission after an initial good response, indicating a need for new treatment strategies to enhance both short-term and long-term efficacy of IVIg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multifocal motor neuropathy: a retrospective study of the response to high-dose intravenous immunoglobulin (IVIg) and current perspectives for diagnosis and treatment]. Léger, JM., Viala, K., Maisonobe, T., et al.[2008]

In a study involving 8 patients with multifocal motor neuropathy (MMN), switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG) over 6 months showed no deterioration in muscle strength or overall health-related quality of life, indicating that SCIG can be a safe alternative to IVIG.

Patients rated the convenience of home treatment with SCIG as extremely good, and while there were some adverse events, only two were moderate, suggesting that SCIG is a well-tolerated option for patients previously stable on IVIG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A smooth transition protocol for patients with multifocal motor neuropathy going from intravenous to subcutaneous immunoglobulin therapy: an open-label proof-of-concept study. Misbah, SA., Baumann, A., Fazio, R., et al.[2011]

In a study of 18 patients with multifocal motor neuropathy treated with high-dose intravenous immunoglobulin (IVIg), 67% showed clinical improvement, with muscle strength increasing by an average of 54.5% over a follow-up period of 9 to 48 months.

While IVIg demonstrated long-term benefits and safety, the effects were often transient, requiring repeated treatments for sustained improvement, and no clear predictive factors for response were identified except for high levels of IgM anti-GM1 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term follow up of multifocal motor neuropathy with conduction block under treatment. Azulay, JP., Rihet, P., Pouget, J., et al.[2019]

Intravenous immunoglobulins (IVIg) are considered the gold standard treatment for multifocal motor neuropathy, supported by multiple randomized, double-blind, placebo-controlled trials.

Despite the initial effectiveness of IVIg, only a small number of patients experience lasting improvement, raising questions about its long-term efficacy and highlighting the need for new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intravenous immunoglobulin in multifocal motor neuropathy. Leger, JM., Vargas, S., Lievens, I.[2007]

In a study of nine patients with multifocal motor neuropathy previously responsive to IV immunoglobulins, treatment with interferon-beta1a showed mixed results, with six patients experiencing no effect and four requiring a return to IVIg due to deterioration.

However, three patients did show significant improvement with interferon-beta1a, particularly those with shorter disease duration and less severe clinical and electrophysiological impairment, suggesting that early intervention may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of multifocal motor neuropathy with interferon-beta1A. Van den Berg-Vos, RM., Van den Berg, LH., Franssen, H., et al.[2019]

References

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

A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy. [2022]

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

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial. [2021]

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

[Multifocal motor neuropathy: a retrospective study of the response to high-dose intravenous immunoglobulin (IVIg) and current perspectives for diagnosis and treatment]. [2008]

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

A smooth transition protocol for patients with multifocal motor neuropathy going from intravenous to subcutaneous immunoglobulin therapy: an open-label proof-of-concept study. [2011]

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

Long term follow up of multifocal motor neuropathy with conduction block under treatment. [2019]

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

Efficacy of intravenous immunoglobulin in multifocal motor neuropathy. [2007]

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

Treatment of multifocal motor neuropathy with interferon-beta1A. [2019]