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

ConditionsCongenital Myasthenic Syndrome CMS

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

Sponsorargenx

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

ARGX-119
Biological/Vaccine
Intravenous infusion of ARGX-119
Placebo
Other intervention
Intravenous infusion of placebo

Treatment groups

16 Participants

are divided into 3 treatment groups

Group A: Double-blinded treatment period - ARGX-119 IVExperimental treatment 1 intervention

Group B: Double-blinded treatment period - Placebo IVPlacebo comparator 1 intervention

Group C: Active-treatment period - ARGX-119 IVExperimental treatment 1 intervention

Trial 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