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

Multifocal Motor Neuropathy Clinical Trial

— ARDA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05225675
• Other study ID #: ARGX-117-2002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 31, 2022
• Est. completion date: October 1, 2024

Study information

• Verified date: February 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multifocal Motor Neuropathy
• Neuritis

Intervention

Biological:
• ARGX-117
Intravenous administration of ARGX-117

Other:
• Placebo
Intravenous administration of placebo

Locations

Country	Name	City	State
Austria	Medizinische Universitat Wien Universitatsklienik fur Neurologie	Vienna
Belgium	AZ Sint-Lucas	Ghent
Canada	Genge Partners Montreal	Québec
Canada	Toronto General Hospital	Toronto
France	CHU de Bordeaux-Hopital Pellegrin	Bordeaux
France	CHRU de Lille-Hopital Roger Salengro	Lille
France	CHU de Nice-Hopital Pasteur 2	Nice
France	Hopital Pitie Salpetriere	Paris
Germany	Katholisches Klinikum Bochum	Bochum
Germany	Universitatsklinikum Essen	Essen
Germany	Universitatsmedzin Gottingen, Klinik fur Neurologie	Göttingen
Germany	Medizinische Hochschule Hannover Klinik Fur Neurologie	Hannover
Germany	Universitatsklinikum Munster	Münster
Italy	IRCCS Ospedale San Raffaele	Milan
Italy	Azienda Ospedaliero Univeritaria Pisana-UOS Neurologia	Pisa
Italy	Azienda Ospedaliera Sant'Andrea-UOS Malattie Neuromuscolari	Rome
Italy	Instituto Clinico Humanitas (IRCCS)	Rozzano
Netherlands	Amsterdam UMC location AMC, Dep of Neurology	Amsterdam
Netherlands	University Medical Centre Utrecht	Utrecht
Poland	Michalscy I Partnerzy Lekarze Spolka Partnerska	Kraków
Poland	Uniwersyteckie centrum kliniczne Warszawskiego	Warsaw
Spain	Hospital de la Santa Creu I Santa Pau -Sevicio Neurologia	Barcelona
Spain	Hospital Universitario Vall d'Herbon	Barcelona
Spain	Hospital Universitari I Politecnic La Fe de Valencia-Servicio Neurologia	Valencia
United Kingdom	Queen Elisabeth University Hospital	Glasgow
United Kingdom	University College London Hospital	London
United Kingdom	Oxford University Hospitals NHS Trust-Jonh Radcliffe Hospital	Oxford
United States	Austin Neuromuscular Center	Austin	Texas
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	NorthShore University HealthSystem	Glenview	Illinois
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	HonorHealth Research Institute-Neuroscience Research	Maitland	Florida
United States	University of Minnesota Delware Clinic Research Unit	Minneapolis	Minnesota
United States	West Virginia University Medicine	Morgantown	West Virginia
United States	Perelman Center for Advanced Medicine-University of Penssylvania	Philadelphia	Pennsylvania
United States	California Pacific Medical Center-Forbes Norris MDA/ALS Research Center	San Francisco	California
United States	HonorHealth Research Institute-Neuroscience Research	Scottsdale	Arizona
United States	University of South Florida Carol and Frank Morsani Center for Advanced Healthcare	Tampa	Florida
United States	George Washington Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety outcomes based on adverse event (AE) monitoring and other safety assessments		16 weeks
Secondary	Time to the first retreatment with IVIg since the final IVIg treatment of the IVIg monitoring period		16 weeks
Secondary	AUC (area under curve) of the change from baseline in mMRC (modified Medical Research Council)-10 sum score		16 weeks
Secondary	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
Secondary	Value baseline in the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Secondary	Change from baseline in the mMRC (modified Medical Research Council)-14 sum score		16 weeks
Secondary	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
Secondary	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
Secondary	AUC (area under curve) of the change from baseline in GS (grip strength)		16 weeks
Secondary	Proportion of participants with a GS (grip strength) decrease of 8 kilopascal (kPa) or more over 3 consecutive days		16 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Values baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)		16 weeks
Secondary	Change from baseline in the Rasch-built overall disability scale for MMN (MMN-RODS©)		16 weeks
Secondary	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
Secondary	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
Secondary	Proportion of participants by level of severity on each dimension of the EQ-5D-5L scale		16 weeks
Secondary	Change from baseline in quality of life using EQ-5D-5L visual analog scale		16 weeks
Secondary	Change from baseline in the chronic acquired polyneuropathy patient-reported index (CAP-PRI)		16 weeks
Secondary	Serum titer levels of binding antibodies (BAbs) against ARGX-117		16 weeks
Secondary	Change from baseline in free C2, total C2, functional complement activity (CH50)		16 weeks
Secondary	Values baseline in free C2, total C2, functional complement activity (CH50)		16 weeks
Secondary	Area Under The Curve (AUC)		16 weeks
Secondary	Maximum serum concentrations (Cmax)		16 weeks