Clinical trial NCT05225675: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multifocal Motor Neuropathy
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2022-02-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Safety outcomes based on adverse event (AE) monitoring and other safety assessments
timeFrame: 16 weeks
Secondary outcomes:
measure: Time to the first retreatment with IVIg since the final IVIg treatment of the IVIg monitoring period
timeFrame: 16 weeks
measure: AUC (area under curve) of the change from baseline in mMRC (modified Medical Research Council)-10 sum score
timeFrame: 16 weeks
measure: 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
timeFrame: 16 weeks
measure: Value baseline in the mMRC (modified Medical Research Council)-14 sum score
timeFrame: 16 weeks
measure: Change from baseline in the mMRC (modified Medical Research Council)-14 sum score
timeFrame: 16 weeks
measure: 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
timeFrame: 16 weeks
measure: Proportion of participants with no deterioration in 2 or more muscle groups as assessed by mMRC (modified Medical Research Council)-14 sum score
timeFrame: 16 weeks
measure: AUC (area under curve) of the change from baseline in GS (grip strength)
timeFrame: 16 weeks
measure: Proportion of participants with a GS (grip strength) decrease of 8 kilopascal (kPa) or more over 3 consecutive days
timeFrame: 16 weeks
measure: Values baseline in GS (grip strength)
timeFrame: 16 weeks
measure: Change from baseline in GS (grip strength)
timeFrame: 16 weeks
measure: Percent change from baseline in GS (grip strength)
timeFrame: 16 weeks
measure: Values baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)
timeFrame: 16 weeks
measure: Change from baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)
timeFrame: 16 weeks
measure: Values baseline in the average time for upper extremity (arm and hand) function (9-Hole Peg Test [9-HPT], or timed Peg Board Test)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: Proportion of participants by level of severity on each dimension of the EQ-5D-5L scale
timeFrame: 16 weeks
measure: Change from baseline in quality of life using EQ-5D-5L visual analog scale
timeFrame: 16 weeks
measure: Change from baseline in the chronic acquired polyneuropathy patient-reported index (CAP-PRI)
timeFrame: 16 weeks
measure: Serum titer levels of binding antibodies (BAbs) against ARGX-117
timeFrame: 16 weeks
measure: Change from baseline in free C2, total C2, functional complement activity (CH50)
timeFrame: 16 weeks
measure: Values baseline in free C2, total C2, functional complement activity (CH50)
timeFrame: 16 weeks
measure: Area Under The Curve (AUC)
timeFrame: 16 weeks
measure: Maximum serum concentrations (Cmax)
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Scottsdate
country: United States
facility: HonorHealth Research Institute-Neuroscience Research
state: Arizona
city: San Francisco
country: United States
facility: California Pacific Medical Center-Forbes Norris MDA/ALS Research Center
state: California
city: Washington
country: United States
facility: George Washington Medical Faculty Associates
state: District of Columbia
city: Maitland
country: United States
facility: HonorHealth Research Institute-Neuroscience Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida Carol and Frank Morsani Center for Advanced Healthcare
state: Florida
city: Glenview
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Minneapolis
country: United States
facility: University of Minnesota Delware Clinic Research Unit
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine-University of Penssylvania
state: Pennsylvania
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Medicine
state: West Virginia
city: Vienna
country: Austria
facility: Medizinische Universitat Wien Universitatsklienik fur Neurologie
city: Ghent
country: Belgium
facility: AZ Sint-Lucas
city: Québec
country: Canada
facility: Genge Partners Montreal
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Bordeaux
country: France
facility: CHU de Bordeaux-Hopital Pellegrin
city: Lille
country: France
facility: CHRU de Lille-Hopital Roger Salengro
city: Nice
country: France
facility: CHU de Nice-Hopital Pasteur 2
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Göttingen
country: Germany
facility: Universitatsmedzin Gottingen, Klinik fur Neurologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover Klinik Fur Neurologie
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Pisa
country: Italy
facility: Azienda Ospedaliero Univeritaria Pisana-UOS Neurologia
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-UOS Malattie Neuromuscolari
city: Rozzano
country: Italy
facility: Instituto Clinico Humanitas (IRCCS)
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC location AMC, Dep of Neurology
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Kraków
country: Poland
facility: Michalscy I Partnerzy Lekarze Spolka Partnerska
city: Warsaw
country: Poland
facility: Uniwersyteckie centrum kliniczne Warszawskiego
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Herbon
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Santa Pau -Sevicio Neurologia
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe de Valencia-Servicio Neurologia
city: Glasgow
country: United Kingdom
facility: Queen Elisabeth University Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust-Jonh Radcliffe Hospital
Study officials:
References: