A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)

A Phase 1b, Double-Blinded, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Efficacy of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes

The purpose of this study is to assess the safety and tolerability of ARGX-119 in adult participants with DOK7- Congenital Myasthenic Syndromes. The study will also assess how ARGX-119 is processed by the body (pharmacokinetics), how the immune system reacts to it (immunogenicity), and how it may improve the way patients feel and function.

After the screening period, eligible participants will be randomized in a 4:1 ratio to receive intravenous infusions of ARGX-119 or placebo during the double-blinded treatment period. Participants will then enter the follow-up period. After the follow-up period, participants may enrol in the active-treatment period, where they will receive open-label ARGX-119.

The full duration of the study is approximately 38 months.

Study Overview

• Status: Recruiting
• Conditions: Congenital Myasthenic Syndrome; CMS
• Intervention / Treatment: Other: Placebo; Biological: ARGX-119

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Study Locations

• Canada
  • Ottawa, Canada, K1Y 4E9
    • Recruiting
    • Ottawa Hospital Research Institute - Civic Campus
    • Contact: Hanns Lochmuller, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
• France
  • Marseille, France, 13385
    • Completed
    • CHU - Hospital de la Timone
  • Paris, France, 75013
    • Recruiting
    • Group Hospitalier Pitie-Salpetriere
    • Contact: Rocio-Nur Villar-Quiles, MD; Phone Number: +33142163791; Email: rocionur.villarquiles@aphp.fr
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Contact: Lorenzo Maggi, MD; Phone Number: +393491237639; Email: lorenzo.maggi@istituto-besta.it
• Spain
  • Valencia, Spain, 46026
    • Active, not recruiting
    • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
• United Kingdom
  • Belfast, United Kingdom, BT16 1RH
    • Recruiting
    • Clinical Trials Centre - South Eastern Health and Social Care Trust - The Ulster Hospital
    • Contact: John McConville, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com
  • Oxford, United Kingdom, OX3 9DU
    • Active, not recruiting
    • John Radcliffe Hospital - Oxford University Hospitals NHS Foundation Trust
• United States
  • California
    • Sacramento, California, United States, 95817
      • Active, not recruiting
      • UC Davis Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann and Robert H Lurie Childrens Hospital of Chicago
      • Contact: Nancy Kuntz, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 18 years of age.
• Has genetically confirmed congenital myasthenic syndromes due to mutation of downstream of kinase 7 (DOK7-CMS).
• Participants taking oral beta agonists (eg, albuterol, salbutamol, ephedrine) must have been receiving the medication for more than 3 months and agree to remain on a same stable dosing regimen of the same medication until the end of the study.

Exclusion Criteria:

• Diagnosis of CMS due to mutation of any gene other than DOK7.
• Known medical condition that would interfere with an accurate assessment of CMS, confound the results of the study, or put the patient at undue risk, as assessed by the investigator.
• History of malignancy, cancer, unless considered cured by adequate treatment with no evidence of recurrence for more than 5 years. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histological findings of prostate cancer.
• Pregnant or lactating state or intention to become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blinded treatment period - ARGX-119 IV; Participants receive ARGX-119 during the double-blinded treatment period	Biological: ARGX-119; Intravenous infusion of ARGX-119
Placebo Comparator: Double-blinded treatment period - Placebo IV; Participants receive placebo during the double-blinded treatment period	Other: Placebo; Intravenous infusion of placebo
Experimental: Active-treatment period - ARGX-119 IV; Participants receive ARGX-119 during the active-treatment period	Biological: ARGX-119; Intravenous infusion of ARGX-119

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of adverse events (AEs)		Up to week 42
Change from active-treatment baseline over time for 6MWT distance	The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. Before and after the 6MWT assessment, the participant's blood pressure, heart rate, and SPO2 will be recorded, and the participant's perception of fatigue and dyspnea will be measured.	Up to 72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed serum concentration (Cmax) of ARGX-119		Up to 42 weeks + 72 weeks
Incidence of ADA against ARGX-119	ADA : anti-drug antibodies	Up to 42 weeks + 72 weeks
Change from baseline over time for key components of the QMG scale	The Quantitative Myasthenia Gravis (QMG) scale is a standardized quantitative scoring system that was developed to assess disease severity based on impairment of body function and structures in patients with MG. Minimum value: 0 (no disease severity); Maximum value: 39 (highest disease severity). The change from active-treatment baseline will be used for the 72 week timepoint.	Up to 42 weeks + 72 weeks
Change from baseline over time for MG-ADL	The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item scale that assesses MG symptoms and their effects on daily activities. Minimum value: 0 (normal symptoms); Maximum value: 24 (most severe symptoms). The change from active-treatment baseline will be used for the 72 week timepoint.	Up to 42 weeks + 72 weeks
Change from baseline over time for PROMIS-GH scale	The Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) is a 10-item participant completed quality of life questionnaire that measures global physical health and mental health. The participant records their response to each question on a 5-point Likert scale, with lower scores indicating poorer health (Minimum value: 0, Maximum value: 20)	Up to 42 weeks
Change from active-treatment baseline over time for 6MWT cadence	The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. Before and after the 6MWT assessment, the participant's blood pressure, heart rate, and SPO2 will be recorded, and the participant's perception of fatigue and dyspnea will be measured.	Up to 72 weeks
Change from active-treatment baseline over time for PROMIS PF-WMA-SF	The PROMIS PF-WMA-SF is an 11-item, participant-completed questionnaire that assesses lower and upper extremity function and associated activities of daily living. The questionnaire asks the participant to rate the items on a 5-point scale of 5 (without any difficulty) to 0 (unable to do).	Up to 72 weeks
Change from active-treatment baseline over time for Neuro-QoL fatigue		Up to 72 weeks
Change from active-treatment baseline over time for FVC		Up to 72 weeks
Change from active-treatment baseline over time for PGI-C		Up to 72 weeks
Change from active-treatment baseline over time for PGI-S		Up to 72 weeks
Change from active-treatment baseline over time for CGI-C		Up to 72 weeks
Change from active-treatment baseline over time for CGI-S		Up to 72 weeks
Change from active-treatment baseline over time for EQ-5D-5L		Up to 72 weeks
Incidence of AEs and SAEs	AE : Adverse events ; SAE : Serious Adverse events	Up to 72 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2024
• Primary Completion (Estimated): August 24, 2027
• Study Completion (Estimated): January 24, 2028

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 31, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neuromuscular Junction Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myasthenic Syndromes, Congenital
• Other Study ID Numbers: ARGX-119-2302; 2023-509872-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No