A Clinical Trial to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of 2 Dose Regimens of ARGX-117 in Adults With Multifocal Motor Neuropathy (ARDA)

A Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 2 Dose Regimens of ARGX-117 in Adults With Multifocal Motor Neuropathy

This is a phase 2, randomized, double-blinded, placebo-controlled, parallel-group, multicenter trial to evaluate the safety and efficacy of 2 dose regimens of ARGX-117 versus placebo, in participants with MMN previously stabilized with IVIg (intravenous immunoglobulin).

Study Overview

• Status: Completed
• Conditions: Multifocal Motor Neuropathy
• Intervention / Treatment: Biological: ARGX-117; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien Universitatsklienik fur Neurologie
• Belgium
  • Ghent, Belgium, 9000
    • AZ Sint-Lucas
• Canada
  • Québec, Canada, H4A 3TA
    • Genge Partners Montreal
  • Toronto, Canada, M5G 2C4
    • Toronto General Hospital
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux-Hopital Pellegrin
  • Lille, France, 59037
    • CHRU de Lille-Hopital Roger Salengro
  • Nice, France, 06001
    • CHU de Nice-Hopital Pasteur 2
  • Paris, France, 75651
    • Hôpital Pitié Salpétrière
• Germany
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Göttingen, Germany, 37075
    • Universitatsmedzin Gottingen, Klinik fur Neurologie
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover Klinik Fur Neurologie
  • Münster, Germany, 48419
    • Universitätsklinikum Münster
• Italy
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Univeritaria Pisana-UOS Neurologia
  • Rome, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea-UOS Malattie Neuromuscolari
  • Rozzano, Italy, 20089
    • Instituto Clinico Humanitas (IRCCS)
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC location AMC, Dep of Neurology
  • Utrecht, Netherlands, 3584 CX
    • University Medical Centre Utrecht
• Poland
  • Krakow, Poland, 31-426
    • Michalscy I Partnerzy Lekarze Spolka Partnerska
  • Warsaw, Poland, 02-097
    • Uniwersyteckie centrum kliniczne Warszawskiego
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Herbon
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu I Santa Pau -Sevicio Neurologia
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe de Valencia-Servicio Neurologia
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elisabeth University Hospital
  • London, United Kingdom, ZC1N 3BG
    • University College London Hospital
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Trust-Jonh Radcliffe Hospital
• United States
  • Arizona
    • Scottsdate, Arizona, United States, 85251
      • HonorHealth Research Institute-Neuroscience Research
  • California
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center-Forbes Norris MDA/ALS Research Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington Medical Faculty Associates
  • Florida
    • Maitland, Florida, United States, 32751
      • HonorHealth Research Institute-Neuroscience Research
    • Tampa, Florida, United States, 33612
      • University of South Florida Carol and Frank Morsani Center for Advanced Healthcare
  • Illinois
    • Glenview, Illinois, United States, 60026
      • Northshore University Healthsystem
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota Delware Clinic Research Unit
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina At Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine-University of Penssylvania
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Neuromuscular Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Capable of giving signed informed consent form (ICF)
2. Male/female at least 18 years of age at the time the informed consent form (ICF) is signed
3. Probable or definite MMN according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) (EFNS/PNS) 2010 guidelines at screening confirmed by the MMN Confirmation Committee (MCC)
4. Receiving a stable IVIg regimen for at least 3 months before screening or recently initiated IVIg treatment
5. IVIg treatment dependency confirmation by the MMN Confirmation Committee (MCC)
6. Immunization with the first meningococcal vaccine and pneumococcal vaccine, and the single Haemophilus influenza type B vaccine must be performed at least 14 days before IMP administration at V1 according to local country-specific immunization schedules. A documented history of vaccination against Neisseria meningitides, Haemophilus influenza type B, and streptococcus pneumonia will be permitted
7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

Exclusion Criteria:

1. Any coexisting condition which may interfere with the outcome assessments
2. Clinical signs or symptoms suggestive for neuropathies other than MMN such as motor neuron disease or other inflammatory neuropathies
3. Severe psychiatric disorder, history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the participant or could affect adherence with the trial protocol.
4. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection during the screening and/or IVIg monitoring period (IVMP).
5. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of MMN or put the participant at undue risk (eg, SLE).

6. History of malignancy unless resolved by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of the IMP. Participants with the following carcinomas will be eligible:

   1. Adequately treated basal cell or squamous cell skin cancer
   2. Carcinoma in situ of the cervix
   3. Carcinoma in situ of the breast
   4. Incidental histological finding of prostate cancer
7. Clinical evidence of other significant serious diseases, have had a recent major surgery (including a splenectomy at any time), or who have any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk

8. Prior/concomitant therapy

   1. Cyclophosphamide and/or rituximab and/or eculizumab and/or mycophenolate mofetil within 3 months prior to screening
   2. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP.

9. Positive serum test at screening for an active viral infection with any of the following conditions:

   1. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection
   2. Hepatitis C virus (HCV) based on HCV antibody assay
   3. HIV based on test results that are associated with an AIDS-defining condition
10. Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse
11. Known hypersensitivity reaction to 1 of the components of the IMP or any of its excipients
12. Female participants with a positive serum or urine pregnancy test, lactating females, and those who intend to become pregnant during the trial or within 15 months after last dose of the IMP
13. ALT or AST ≥2 × upper limit of normal and total bilirubin ≥1.5 × upper limit of normal of the central laboratory reference range
14. An estimated glomerular filtration rate of ≤60 mL/min/1.73m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARGX-117; Intravenous administration of ARGX-117	Biological: ARGX-117; Intravenous administration of ARGX-117
Placebo Comparator: Placebo; Intravenous administration of placebo	Other: Placebo; Intravenous administration of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs and SAEs	AE : Adverse Events, SAE: Serious Adverse Events	Up to 80 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the First Retreatment With IVIg	The time to first retreatment with intravenous immunoglobulin (IVIg) is defined as the time from the last IVIg administration before randomization until the first IVIg retreatment during the 16-week treatment period	Up to 16 weeks
Time-to-relapse	Time-to-relapse is defined as the time from randomization until a participant met the threshold for clinically meaningful deterioration	Up to 16 weeks
iAUC of the Change From Baseline in mMRC-10 Sum Score	The Modified Medical Research Council (mMRC)-10 sum score assesses muscle strength of 10 muscles groups, both sides (left and right). A score between 0 (paralysis) and 5 (normal strength) is assigned for each muscle group. A higher value indicates better muscle strength. The total score, ranging from 0 to 100, is based on the sum of both the left and right side of the body. The Incremental Area Under Curve (iAUC) is the area under the curve of the change from baseline in the Modified Medical Research Council (mMRC)-10 score. A positive AUC indicates a favorable outcome while a negative AUC indicates an unfavorable outcome.	Up to 16 weeks
Change From Baseline in the Average Score of the 2 Most Important Muscle Groups as Assessed by the mMRC-14 Sum Score	The Modified Medical Research Council (mMRC)-14 assesses muscle strength of 14 muscles groups, both sides (left and right). A score between 0 and 5 (normal strength) is assigned. This endpoint is the change from baseline in the average score of the 2 most important muscle groups affected by the disease. It ranges between 0 and 5. A change of more than 0 represents an improvement in strength, and a change less than 0 represents worsening.	At week 16
Change From Baseline in the mMRC-14 Sum Score	The Modified Medical Research Council (mMRC)-14 scores range from 0 to 140 with a higher score representing better muscle strength. A change of more than 0 represents an improvement in strength, and a change less than 0 represents worsening.	At week 16
Proportion of Participants Showing a Deterioration of at Least 2 Points as Assessed by the mMRC-10 Sum Score	The Modified Medical Research Council (mMRC)-10 scores evaluates motor strength/weakness from 10 predetermined muscle groups. A higher proportion of participants showing a deterioration represents a worsening of the outcome.	Up to 16 weeks
iAUC of the Change From Baseline in GS Daily Average	Measurement of grip strength (GS) has been done using the Martin vigorimeter in kPa. The incremental Area Under Curve (iAUC) is the area under the curve of the change from baseline of GS daily average. The 3 daily measurements of GS from the left hand and the 3 daily measurements of GS from the right hand have been recorded and the daily average for the left hand and right hand has been calculated, respectively.	Up to 16 weeks
Percent Change From Baseline in GS 3-day Moving Average	Measurement of grip strength (GS) has been done using the Martin vigorimeter in kPa. The 3 daily measurements of GS from the left hand and the 3 daily measurements of GS from the right hand have been recorded and the daily average for the left hand and right hand has been calculated, respectively. A 3-day moving average has been generated based on the average over the last 3 days of the obtained daily averages for each hand.	At week 16
Change From Baseline in the MMN-RODS Centile Score	The Rasch-built Overall Disability Scale for MMN (MMN-RODS) is a disease-specific PRO instrument constructed to capture activity limitations in patients with MMN. Raw sum scores of the 25-item MMN-RODS (range, 0-50) were converted to a centile metric score ranging from 0 to 100. Lower scores indicated a greater degree of disability.	At week 16
Percent Change From Baseline in the Average Time for Upper Extremity (Arm and Hand) Function	The 9-Hole Peg Test (9-HPT) results are based on the time to complete the assessment with a shorter time representing better muscle strength. A change of less than 0 represents an improvement in strength, and a change more than 0 represents worsening.	At week 16
Proportion of Participants by Level of Severity on Each Dimension of the EQ-5D-5L Scale	The EuroQol 5-Dimension 5-Level (EQ-5D-5L) scale includes five dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension is ranked with a level 1-5 with level 1 being no problems and level 5 representing extreme problems.	At week 16
Change From Baseline in Quality of Life Using EQ-5D-5L Visual Analog Scale	The EQ-5D-5L visual analog scale is from 0-100 with 0 representing the worst health. A change of more than 0 represents an improvement in health, and a change of less than 0 represents worsening.	At week 16
Change From Baseline in the CAP-PRI	The Chronic Acquired Polyneuropathy Patient-reported Index (CAP-PRI) assesses disease-specific quality of life. This instrument includes the assessment of 15 items yielding a total score ranging from 0 to 30. A change of less than 0 represents an improvement in health, and a change more than 0 represents worsening.	At week 16
Proportion of Participants by Level of Improvement Using the PGI-C Scale	Patient Global Impression of Change (PGI-C) scale ranks a patients condition from 1-7 with 1 representing the most improvement and 7 representing the most decline in their condition.	Up to 16 weeks
Change From Baseline in the 9-item FSS Average Total Score	9-item Fatigue Severity Scale (FSS) average score is the sum of the 9 items divided by the number of items. It ranges from 0 to 7 a higher score representing more severe fatigue. A change of less than 0 indicates an improvement.	Up to 16 weeks
Percent of Total Hours for Work-related and Household Chore Activities Lost, as Part of the HRPQ	The Health-Related Productivity Questionnaire (HRPQ) provides data related to missed hours at work or educational activities and reduced effectiveness during any attempted work.	Up to 16 weeks
Change From Baseline in Effectiveness, Side Effects, Convenience, and Overall Satisfaction Scores as Assessed by the TSQM-14	Each Treatment Satisfaction Questionnaire for Medication-14 items (TSQM-14) domain score ranges from 0-100 with higher scores representing greater satisfaction with the treatment. A change greater than 0 indicates an improvement in satisfaction.	Up to 16 weeks
Maximum Empasiprubart Serum Concentrations (Cmax)		Up to 16 weeks
Percent Change From Baseline in Free C2, Total C2, and Functional Complement Activity (CH50)		At week 16
Incidence of Antidrug Antibodies (ADA) Against Empasiprubart		Up to 16 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): June 4, 2024
• Study Completion (Actual): June 4, 2024

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuritis
• Other Study ID Numbers: ARGX-117-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No