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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Multifocal Motor Neuropathy

Intervention / Treatment
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* Biological: ARGX-117
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent form (ICF) Male/female at least 18 years of age at the time the informed consent form (ICF) is signed 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) Receiving a stable IVIg regimen for at least 3 months before screening or recently initiated IVIg treatment IVIg treatment dependency confirmation by the MMN Confirmation Committee (MCC) 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 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: Any coexisting condition which may interfere with the outcome assessments Clinical signs or symptoms suggestive for neuropathies other than MMN such as motor neuron disease or other inflammatory neuropathies 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. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection during the screening and/or IVIg monitoring period (IVMP). 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). 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: Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histological finding of prostate cancer 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 Prior/concomitant therapy Cyclophosphamide and/or rituximab and/or eculizumab and/or mycophenolate mofetil within 3 months prior to screening Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP. Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indicative of an acute or chronic infection Hepatitis C virus (HCV) based on HCV antibody assay HIV based on test results that are associated with an AIDS-defining condition Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse Known hypersensitivity reaction to 1 of the components of the IMP or any of its excipients 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 ALT or AST ≥2 × upper limit of normal and total bilirubin ≥1.5 × upper limit of normal of the central laboratory reference range An estimated glomerular filtration rate of ≤60 mL/min/1.73m2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARGX-117<br>Intravenous administration of ARGX-117 | Biological: ARGX-117<br>* Intravenous administration of ARGX-117<br>|
| Placebo Comparator: Placebo<br>Intravenous administration of placebo | Other: Placebo<br>* Intravenous administration of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |