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

Phase 1RecruitingNCT06436742

argenx16 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Congenital Myasthenic Syndrome CMS

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (9)

UC Davis Medical Center

Sacramento, California, United States

ACTIVE_NOT_RECRUITING

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

RECRUITING

Ottawa Hospital Research Institute - Civic Campus

Ottawa, Canada

RECRUITING

CHU - Hospital de la Timone

Marseille, France

COMPLETED

Group Hospitalier Pitie-Salpetriere

Paris, France

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

RECRUITING

Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

Valencia, Spain

ACTIVE_NOT_RECRUITING

Clinical Trials Centre - South Eastern Health and Social Care Trust - The Ulster Hospital

Belfast, United Kingdom

RECRUITING

John Radcliffe Hospital - Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

ACTIVE_NOT_RECRUITING

Outcomes

Primary Outcomes

Assessment of adverse events (AEs)

Time frame: 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.

Time frame: Up to 72 weeks

Secondary Outcomes

Maximum observed serum concentration (Cmax) of ARGX-119

Time frame: Up to 42 weeks + 72 weeks

Incidence of ADA against ARGX-119

ADA : anti-drug antibodies

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: Up to 42 weeks

Change from active-treatment baseline over time for 6MWT cadence

Time frame: 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).

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for Neuro-QoL fatigue

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for FVC

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for PGI-C

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for PGI-S

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for CGI-C

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for CGI-S

Time frame: Up to 72 weeks

Change from active-treatment baseline over time for EQ-5D-5L

Time frame: Up to 72 weeks

Incidence of AEs and SAEs

AE : Adverse events ; SAE : Serious Adverse events

Time frame: Up to 72 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (9)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts