Clinical Study in Multifocal Motor Neuropathy (MMN)
CLINICALTRIALS.GOV ID: NCT05225675
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
About Multifocal Motor Neuropathy (MMN)
MMN is a chronic, rare, immune-mediated neuropathy characterized by progressive asymmetric weakness and atrophy without sensory abnormalities. Complement deposition leads to the disruption of Schwann cell-axolemma junctions, ion-channel clustering, and membrane integrity at the nodal and paranodal regions, leading to demyelination and motor nerve conduction block.
In MMN, IgM anti-GM1 autoantibodies bind to motor neurons and activate the classical complement pathway, leading to damage to the neurons. This pathway is dependent on complement factor 2 (C2)1
Artist representation of antibodies attacking and binding to motor neuron.
Adapted from 1. Budding K, et al. Neurol Neuroimmunol Neuroinflamm 2022;9:e1107
About the Investigational Therapy
ARGX-117 is the investigational study drug in ARDA and is being investigated as a complement inhibitor monoclonal antibody against complement factor 2 (C2).
ARGX-117 is not approved for use in multifocal motor neuropathy (MMN) by any regulatory agency, as its safety and effectiveness have not been established for the treatment of MMN.
A Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group, Multicenter Study
Study Objectives
Primary Objective
To evaluate the safety and tolerability of ARGX-117 compared to placebo in adult participants previously stabilized with IVIg.
Secondary Objective
To evaluate the efficacy of ARGX-117 compared to placebo on muscle strength and/or motor function in adult participants previously stabilized with IVIg
Study Design
Screening Period: up to 4 weeks
IVIg Dependency Period (IVDP): up to 15 weeks
Only participants whose IVIg dependency is uncertain will enter the IVIg dependency period to assess the impact of a delayed IVIg administration on grip strength (GS) and/or motor function.
IVIg Monitoring Period (IVMP): 5-11 weeks
The IVMP (all participants) includes 3 IVIg treatment cycles and participants will receive IVIg at a frequency, duration, and dose established by their medical history.
Double-Blinded Treatment Period (DBTP): 16 weeks
Participants will be randomized on day 1 of the DBTP in a 2:1 ratio to ARGX-117 or placebo and randomization will be stratified based on an individual’s IVIg dose frequency. Participants will be retreated with IVIg during the DBTP if there is a clinically meaningful deterioration in muscle strength and/or motor function.
Long Term Extension (LTE) Study
After completing the 16-week DBTP, participants may enroll in a long-term extension (LTE) study and receive ARGX-117.
OR
Safety Follow-Up Period: 12 months
The safety follow-up period will characterize safety, PK, and PD during the elimination of ARGX-117.
Treatment:
Investigational Medicinal product (IMP) includes:
ARGX-117 administered by IV infusion
Placebo administered by IV infusion over approximately 2 hours at visit 1 and approximately 1 hour for all subsequent administrations.
IV infusions will be administered over approximately 2 hours at visit 1 and approximately 1 hour for all subsequent administrations
Two dose regimens will be investigated in this trial:
Cohort 1:
A single dose of 30 mg/kg ARGX-117 or placebo on day 1 followed by 4 weekly doses of 10 mg/kg ARGX-117 or placebo on days 8, 15, 22, and 29 (4 infusions in total) and a dose of 10 mg/kg ARGX-117 or placebo every 2 weeks until the end of the DBTP, starting from day 43 (5 infusions in total).
Cohort 2:
A single dose of 60 mg/kg ARGX-117 or placebo on day 1 followed by 4 weekly doses of 30 mg/kg ARGX-117 or placebo on days 8, 15, 22 and 29 (4 infusions in total) and a dose of 30 mg/kg ARGX-117 or placebo every 2 weeks until the end of the DBTP, starting from day 43 (5 infusions in total).
Key Eligibility Criteria
INCLUSION CRITERIA*
Male/female at least 18 years of age
Probable or definite MMN according to the EFNS/PNS 2010 guidelines
Receiving a stable IVIg regimen before screening, and both of the following:
IVIg treatment interval of 2 to 5 weeks
IVIg dose of 0.4 to 2.0 grams per kg body weight and infusion
Participants must be agreeable to standard of care immunizations prior to treatment period
Participants must be agreeable to contraceptive methods as indicated, throughout the study period.
EXCLUSION CRITERIA*
Clinical signs or symptoms suggestive for neuropathies other than MMN such as motor neuron disease (eg, bulbar signs or brisk reflexes) or other inflammatory neuropathies
Any other known neuropathies, physical impairments, or 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
Recent history of cancer (w/in 3 years), except for : basal or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or 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. Liver enzymes ≥2 × upper limit of normal and total bilirubin ≥1.5 × upper limit of normal range. An estimated glomerular filtration rate of ≤60 mL/min/1.73m2
Cyclophosphamide and/or rituximab and/or eculizumab and/or mycophenolate mofetil within 3 months prior to screening
*Other criteria apply.
Please see clinicaltrials.gov NCT05225675 for more information about the study, including the full inclusion and exclusion criteria.
To contact us or to speak to an investigator, or to refer a patient to the ARDA Study, please complete the form below:
References:
1. Budding K, et al. Neurol Neuroimmunol Neuroinflamm 2022;9:e1107. doi:10.1212/NXI.0000000000001107
2. Data on file, argenx 2022
3. https://clinicaltrials.gov/ct2/show/NCT05225675
ARGX-117-2002_HCP Webpage_V1_R3_09DEC2022_US
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