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: Active, not recruiting
• Conditions: Multifocal Motor Neuropathy
• Intervention / Treatment: Biological: ARGX-117; Other: Placebo

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

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

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
    • Hopital Pitie Salpetriere
• Germany
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
  • Göttingen, Germany, 37075
    • Universitatsmedzin Gottingen, Klinik fur Neurologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover Klinik Fur Neurologie
  • Münster, Germany, 48419
    • Universitatsklinikum Munster
• 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
  • Kraków, 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
    • Scottsdale, 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, 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	Time Frame
Safety outcomes based on adverse event (AE) monitoring and other safety assessments	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first retreatment with IVIg since the final IVIg treatment of the IVIg monitoring period		16 weeks
AUC (area under curve) of the change from baseline in mMRC (modified Medical Research Council)-10 sum score		16 weeks
Value baseline in the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Change from baseline in the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Proportion of participants showing a deterioration of 1 or more points in at least 2 muscle groups as assessed by the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Proportion of participants with no deterioration in 2 or more muscle groups as assessed by mMRC (modified Medical Research Council)-14 sum score		16 weeks
AUC (area under curve) of the change from baseline in GS (grip strength)		16 weeks
Proportion of participants with a GS (grip strength) decrease of 8 kilopascal (kPa) or more over 3 consecutive days		16 weeks
Values baseline in GS (grip strength)	The baseline for the grip strength is a 3-day moving average per hand, measured as an average of 3 contractions daily, each lasting 3 seconds. Measurement of GS will be done using the Martin vigorimeter in kPa.	16 weeks
Change from baseline in GS (grip strength)	The baseline for the grip strength is a 3-day moving average per hand, measured as an average of 3 contractions daily, each lasting 3 seconds. Measurement of GS will be done using the Martin vigorimeter in kPa.	16 weeks
Percent change from baseline in GS (grip strength)	The baseline for the grip strength is a 3-day moving average per hand, measured as an average of 3 contractions daily, each lasting 3 seconds. Measurement of GS will be done using the Martin vigorimeter in kPa.	16 weeks
Values baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)		16 weeks
Change from baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)		16 weeks
Serum titer levels of binding antibodies (BAbs) against ARGX-117		16 weeks
Change from baseline in free C2, total C2, functional complement activity (CH50)		16 weeks
Values baseline in free C2, total C2, functional complement activity (CH50)		16 weeks
Area Under The Curve (AUC)		16 weeks
Maximum serum concentrations (Cmax)		16 weeks
Change from baseline in the average score of the 2 most important muscle groups as assessed by the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Values baseline in the average time for upper extremity (arm and hand) function (9-Hole Peg Test [9-HPT], or timed Peg Board Test)		16 weeks
Change from baseline in the average time for upper extremity (arm and hand) function (9-Hole Peg Test [9-HPT], or timed Peg Board Test)		16 weeks
Proportion of participants by level of severity on each dimension of the EQ-5D-5L scale		16 weeks
Change from baseline in quality of life using EQ-5D-5L visual analog scale		16 weeks
Change from baseline in the chronic acquired polyneuropathy patient-reported index (CAP-PRI)		16 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 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): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

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