A Clinical Trial to Investigate the Long-term Safety and Tolerability, Efficacy, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of ARGX-117 in Adults With Multifocal Motor Neuropathy

Multifocal Motor Neuropathy (MMN) Clinical Trial

— ARDA+  

Official title:

A Long-term Extension of the ARGX-117-2002 Trial to Evaluate the Long-term Safety and Tolerability, Efficacy, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of ARGX-117 in Adults With Multifocal Motor Neuropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05405361
• Other study ID #: ARGX-117-2003
• Status: Recruiting
• Phase: Phase 2
• Start date: January 18, 2023
• Est. completion date: October 1, 2026

Study information

• Verified date: April 2024
• Source: argenx
• Contact: Sabine Coppieters, MD
• Phone: 857-350-4834
• Email: ClinicalTrials[@]argenx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is an extension of the antecedent trial ARGX-117-2002. It is a multicenter trial that has been designed to evaluate the long-term safety and tolerability, efficacy, immunogenicity, Pharmacokinetics (PK), and Pharmacodynamics (PD) of ARGX-117 Intravenously (IV) in adults with Multifocal Motor Neuropathy (MMN). The trial will include a double-blinded rollover treatment period (DTP), an open-label treatment period (OTP), and a safety follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: October 1, 2026
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Capable of providing signed informed consent and complying with protocol requirements. Participants must be able to read and write.

2. Must have completed the double-blinded treatment period of the ARGX-117-2002 trial and considered to be eligible for treatment with ARGX-117

3. Agrees to use contraceptive measures consistent with local regulations and the

following:

1. Male participants: must use an acceptable contraceptive method that should be maintained at minimum until 15 months after last dose of Investigational Medicinal Product (IMP).

2. Female participants (women) of childbearing potential must have a negative urine pregnancy test at baseline before Investigational Medicinal Product can be administered.

Exclusion Criteria:

1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection.

2. Clinical evidence of other significant serious diseases, have had a recent major surgery, 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.

3. Currently participating in another interventional clinical study.

4. Pregnant or lactating or intend to become pregnant during the trial or within 15 months after last dose of the Investigational Medicinal Product.

Related Conditions & MeSH terms

• Multifocal Motor Neuropathy (MMN)
• 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 (Medical University of Vienna)	Vienna
Belgium	AZ Sint-Lucas	Gent
Canada	University Health Network	Toronto
France	CHU Bordeaux - Groupe Hospitalier Pellegrin	Bordeaux
France	Hôpital Roger Salengro (CHU de Lille)	Lille
France	CHU de Nice	Nice
France	Hôpital de la Pitié Salpétrière	Paris
Germany	Universitätsklinikum Essen	Essen
Germany	Universitatsmedizin Gottingen (UMG) Georg-August-Universitaet	Göttingen
Italy	IRCCS Ospedale San Raffaele S.r.l.	Milano
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Sant' Andrea	Rome
Italy	IRCCS Humanitas Research Hospital	Rozzano
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Michalski i Partnerzy Lekarze Spolka Partnerska	Kraków
Poland	Warszawski Uniwersytet Medyczny	Warsaw
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Oxford University Hospitals NHS Trust	Oxford
United States	Austin Neuromuscular Center	Austin	Texas
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	NorthShore University HealthSystem	Glenview	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	HonorHealth Neurology	Scottsdale	Arizona

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.		Until marketing authorization of ARGX-117, assessed up to 70 months or treatment discontinuation, whichever comes first
Secondary	Value from baseline in the modified Medical Research Council (mMRC) -10 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the modified Medical Research Council (mMRC) -10 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants showing a deterioration of at least 2 points in Medical Research Council (mMRC)-10 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation
Secondary	Value from baseline in the modified Medical Research Council (mMRC) -14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the modified Medical Research Council (mMRC) -14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation
Secondary	Proportion of participants showing a deterioration of at least 2 points in the Medical Research Council (mMRC)-14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants showing a deterioration of 1 or more points in at least 2 muscle groups as assessed by the Medical Research Council (mMRC)-14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation
Secondary	Proportion of participants with no deterioration in 2 or more muscle groups as assessed by Medical Research Council (mMRC)-14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Value from baseline in the average score of the 2 most important muscle groups as assessed by the Medical Research Council (mMRC)-14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the average score of the 2 most important muscle groups as assessed by the Medical Research Council (mMRC)-14 sum score	The mMRC sum score evaluates motor strength/weakness from predetermined muscle groups (upper and lower limbs). The higher the score, the better the muscle strength.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation
Secondary	Values from baseline in grip strength (GS)	GS measurement consists of 3 repeated contractions with the participant's maximal effort. The duration of each contraction will be 3 seconds. Each test begins with gripping with the right hand followed by the left. Measurement of GS will be done using the Martin vigorimeter in kPa.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in grip strength (GS)	GS measurement consists of 3 repeated contractions with the participant's maximal effort. The duration of each contraction will be 3 seconds. Each test begins with gripping with the right hand followed by the left. Measurement of GS will be done using the Martin vigorimeter in kPa.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation
Secondary	Percent change from baseline in grip strength (GS)	GS measurement consists of 3 repeated contractions with the participant's maximal effort. The duration of each contraction will be 3 seconds. Each test begins with gripping with the right hand followed by the left. Measurement of GS will be done using the Martin vigorimeter in kPa.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants with a decline of >30% in grip strength (GS).	GS measurement consists of 3 repeated contractions with the participant's maximal effort. The duration of each contraction will be 3 seconds. Each test begins with gripping with the right hand followed by the left. Measurement of GS will be done using the Martin vigorimeter in kPa.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants with a grip strength (GS) decrease of 8 kilopascals (kPa) or more.	GS measurement consists of 3 repeated contractions with the participant's maximal effort. The duration of each contraction will be 3 seconds. Each test begins with gripping with the right hand followed by the left. Measurement of GS will be done using the Martin vigorimeter in kPa.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values from baseline in the Rasch-built overall disability scale for Multifocal Motor Neuropathy (MMN-RODS©).	MMN-RODS© consists of 25 items that are scored 0 (unable to perform), 1 (able to perform, but with difficulty), or 2 (able to perform without difficulty) for each item, yielding a total score from 0 to 50.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the Rasch-built overall disability scale for Multifocal Motor Neuropathy (MMN-RODS©).	MMN-RODS© consists of 25 items that are scored 0 (unable to perform), 1 (able to perform, but with difficulty), or 2 (able to perform without difficulty) for each item, yielding a total score from 0 to 50.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values from baseline in the average time for the upper extremity (arm and hand) function (9-Hole Peg Test [9-HPT], or timed pegboard test).	The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and nondominant hands will be tested twice (2 consecutive trials of the dominant hand, followed immediately by 2 consecutive trials of the nondominant hand).	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the average time for the upper extremity (arm and hand) function (9-Hole Peg Test [9-HPT], or timed pegboard test).	The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and nondominant hands will be tested twice (2 consecutive trials of the dominant hand, followed immediately by 2 consecutive trials of the nondominant hand).	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants by level of severity on each dimension of the Euro-Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) scale.	The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores for each dimension include 5 levels: no problem, slight problem, moderate problem, severe problem, and extreme problem.	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Value from baseline in EQ-5D-5L visual analog scale (VAS).	A vertical VAS is included in the EQ-5D-5L. Participants mark their health status from 0 (the worst health you can imagine) to 100 (the best health you can imagine).	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in EQ-5D-5L visual analog scale (VAS).	A vertical VAS is included in the EQ-5D-5L. Participants mark their health status from 0 (the worst health you can imagine) to 100 (the best health you can imagine).	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values from baseline in the Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI).	The Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI) includes the assessment of 15 items. Items will be scored 0 (not at all), 1 (a little bit), or 2 (a lot), yielding a total score that ranges from 0 to 30	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI).	The Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI) includes the assessment of 15 items. Items will be scored 0 (not at all), 1 (a little bit), or 2 (a lot), yielding a total score that ranges from 0 to 30.	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values from baseline in the 9-item Fatigue Severity Scale (FSS).	Fatigue levels are rated from 1 to 7. A low value indicates that the statement is not very appropriate whereas a high value indicates agreement.	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in the 9-item Fatigue Severity Scale (FSS).	Fatigue levels are rated from 1 to 7. A low value indicates that the statement is not very appropriate whereas a high value indicates agreement.	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Value change as assessed by the Patient Global Impression of Change (PGIC) scale.	PGIC is a 7-point scale depicting a participant's rating of overall improvement. The lower the score, the better the improvement.	On day 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Proportion of participants by level of severity of MMN as assessed by the Patient Global Impression of Severity (PGIS).	PGIS is a 7-point scale depicting a participant's rating of overall illness severity. Higher scores mean a higher severity.	On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values for work-related and household chore activities of the Health-Related Productivity Questionnaire (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. These criteria form an important portion of work-related productivity and will be used to assess health-related and work-related productivity in the trial.	On day 1 and 15 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Area Under The Curve (AUC).		On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Maximum serum concentrations (Cmax).		On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Values from baseline in free C2, total C2, functional complement activity (CH50).		On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Change from baseline in free C2, total C2, functional complement activity (CH50).		On day 1, 8, 15, 22 followed by every 4 weeks during 12 weeks followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Incidence of antidrug antibodies (ADA) against ARGX-117.		On day 1, 15, 29, 113 followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.
Secondary	Prevalence of antidrug antibodies (ADA) against ARGX-117.		On day 1, 15, 29, 113 followed by every 8 weeks until market authorization of ARGX-117, assessed up to 70 months or treatment discontinuation.