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

argenx54 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Multifocal Motor Neuropathy

Interventions

ARGX-117BIOLOGICAL

Intravenous administration of ARGX-117

PlaceboOTHER

Intravenous administration of placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (40)

Outcomes

Primary Outcomes

Number of Participants With AEs and SAEs

AE : Adverse Events, SAE: Serious Adverse Events

Time frame: Up to 80 weeks

Secondary Outcomes

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

Time frame: 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

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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HonorHealth Research Institute-Neuroscience Research

Scottsdate, Arizona, United States

California Pacific Medical Center-Forbes Norris MDA/ALS Research Center

San Francisco, California, United States

George Washington Medical Faculty Associates

Washington D.C., District of Columbia, United States

HonorHealth Research Institute-Neuroscience Research

Maitland, Florida, United States

University of South Florida Carol and Frank Morsani Center for Advanced Healthcare

Tampa, Florida, United States

NorthShore University HealthSystem

Glenview, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Minnesota Delware Clinic Research Unit

Minneapolis, Minnesota, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

...and 30 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 16 weeks

Maximum Empasiprubart Serum Concentrations (Cmax)

Time frame: Up to 16 weeks

Percent Change From Baseline in Free C2, Total C2, and Functional Complement Activity (CH50)

Time frame: At week 16

Incidence of Antidrug Antibodies (ADA) Against Empasiprubart

Time frame: Up to 16 weeks