Empasiprubart vs IVIg for Multifocal Motor Neuropathy

(Empassion Trial)

Recruiting at 87 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

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, empasiprubart (a new potential drug) and IVIg (intravenous immunoglobulin), for individuals with multifocal motor neuropathy (MMN), a condition affecting the nerves and causing muscle weakness. In the first part of the trial, participants will receive either empasiprubart or IVIg, along with a placebo (a substance with no therapeutic effect). Later, they may receive only empasiprubart. The study seeks adults diagnosed with MMN who have responded to IVIg in the past five years and are currently on a stable IVIg treatment plan. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, empasiprubart showed promise in treating multifocal motor neuropathy (MMN). Research has indicated that patients generally tolerated empasiprubart well. Some studies noted improvements in grip strength and a reduced need for IVIg retreatment, suggesting it might help manage symptoms.

Regarding safety, earlier trials reported no major concerns. However, side effects can differ from person to person. Prospective participants should discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for multifocal motor neuropathy (MMN), which typically involves intravenous immunoglobulin (IVIg), empasiprubart offers a novel approach. This investigational drug works differently by potentially targeting specific pathways involved in nerve function, rather than relying on the broad immunomodulation offered by IVIg. Researchers are particularly excited about empasiprubart because it could provide a more targeted effect, potentially leading to improved outcomes with fewer side effects. Moreover, empasiprubart may offer a simpler administration method compared to the frequent infusions required with IVIg, potentially improving convenience and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for MMN?

Research has shown that empasiprubart may help treat multifocal motor neuropathy (MMN). In this trial, participants will receive either empasiprubart or IVIg in different phases. Previous studies found that patients taking empasiprubart needed fewer IVIg treatments, a common therapy for MMN. This suggests that empasiprubart might reduce the frequency of treatments. Patients also reported stronger grip strength and improved well-being. These results indicate that empasiprubart could be effective for MMN. Meanwhile, IVIg remains a standard treatment known for effectively managing MMN symptoms. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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]

Citations

1. argenxmedical.com argenxmedical.com/content/dam/medical-affairs/congress-posters/nuerology/mmn/pns/Empasiprubart%20%28ARGX-117%29%20in%20Multifocal%20Motor%20Neuropathy%20Initial%20Safety%20and%20Efficacy%20Data%20of%20the%20Phase%202%20ARDA%20Study.pdf

Empasiprubart (ARGX-117) in Multifocal Motor Neuropathy Empasiprubart (ARGX-117) in Multifocal. Motor Neuropathy: Initial Safety and. Efficacy Data of the Phase 2 ARDA Study. W. Ludo van der Pol,1 ...

2. neurologylive.com neurologylive.com/view/phase-2-arda-findings-support-empasiprubart-multifocal-motor-neuropathy

Phase 2 ARDA Findings Support Development ... Empasiprubart showed safety and reduced IVIg retreatment need in MMN patients, with improved grip strength and condition perception. The agent ...

3. argenx.com argenx.com/news/2024/argenx-highlights-breadth-autoimmune-pipeline-new-multifocal-motor-neuropathy-data-2024

argenx Highlights Breadth of Autoimmune Pipeline with ... Improved function and reduced risk of IVIg retreatment: Compared with placebo, treatment with empasiprubart reduced the risk of IVIg retreatment ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06742190

NCT06742190 | A Study to Assess the Efficacy and Safety ... 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 ...

5. argenx.com argenx.com/content/dam/argenx-corp/media-documents/ARGX_MMN_Interim_Results.pdf

argenx Initiates Second Cohort of Phase 2 ARDA Study of ... An early efficacy assessment of all 22 patients supports proof-of-concept of empasiprubart in MMN. The data showed distinct separation between treated patients ...

6. argenxmedical.com argenxmedical.com/content/dam/medical-affairs/congress-posters/nuerology/nmsg2024/Empasiprubart%20(ARGX-117)%20in%20Multifocal%20Motor%20Neuropathy_Initial%20Safety%20and%20Efficacy%20Data%20of%20the%20Phase%202%20ARDA%20Study.pdf

Initial Safety and Efficacy Data of the Phase 2 ARDA Study Slight imbalances were observed in median age, grip strength, MMN-RODS score, and CAP-PRI score between treatment arms, with lower disease-specific QoL and ...