Clinical trial NCT06436742: A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants with DOK7-Congenital Myasthenic Syndromes (CMS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Congenital Myasthenic Syndrome
Lead sponsor: argenx
Sponsor class: INDUSTRY
First posted: 2024-05-31
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 treatment period. Participants will then enter the follow-up period. The full duration of the study is approximately 11 months.


Eligibility criteria: 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.
* Different study drug received in another clinical study within 12 weeks or 5 half-lives before screening.
* Current participation in another interventional clinical study or prior participation in any gene therapy or cell therapy study.
* Pregnant or lactating state or intention to become pregnant during the study.

The complete list of exclusion criteria can be found in the protocol.

Primary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: Up to week 42
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax) of ARGX-119
timeFrame: Up to week 42
measure: Incidence of anti-drug antibodies (ADA) against ARGX-119
timeFrame: Up to week 42
measure: Prevalence of anti-drug antibodies (ADA) against ARGX-119
timeFrame: Up to week 42
measure: Change from baseline over time for key components of the Quantitative Myasthenia Gravis (QMG) scale
timeFrame: Up to week 42
measure: Change from baseline over time for Myasthenia Gravis Activities of Daily Living (MG-ADL)
timeFrame: Up to week 42
measure: Change from baseline over time for Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) scale
timeFrame: Up to week 42
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute - Civic Campus
city: Marseille
country: France
facility: CHU - Hospital de la Timone
city: Paris
country: France
facility: Group Hospitalier Pitie-Salpetriere
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Valencia
country: Spain
facility: Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital - Oxford University Hospitals NHS Foundation Trust
Study officials:
References: