This is a Phase Ib, open-label, dose-escalation, single-center/multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of multiple doses of EA5 (a humanized anti-complement C5 monoclonal antibody) in adult participants with anti-AChR antibody-positive generalized myasthenia gravis (gMG) who have not previously received complement inhibitor therapy. Approximately 18 participants will be enrolled. The study consists of a screening period (Day -42 to Day -1), a loading period (Day 1 to Day 14), a treatment observation period (Day 15/Week 3 to Day 99/Week 15), and an end-of-study visit (up to Day 155/Week 23). All participants receive a loading does , then are assigned to one of three maintenance dose cohorts: Cohort 1 (Low Dose), Cohort 2 (MID Dose), and Cohort 3 (High Dose). The primary objective is to assess safety and tolerability. Secondary objectives include preliminary efficacy, PK, PD (complement inhibition), and immunogenicity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W).
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W).
First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 4 weeks(Q4W).
Beijing Hospital
Beijing, Beijing Municipality, China
Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline up to Week 14
Change and percentage change from baseline in MG-ADL total score.
The proportion of participants who achieve the Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) response , along with the 2-sided 95% CI
Time frame: Weeks 2, 4, 8, and 12
Change and percentage change from baseline in QMG total score.
The mean change of quantitative myasthenia gravis (QMG) total score,along with 2-sided 95% CI
Time frame: Weeks 2, 4, 8, and 12
Change and percentage change from baseline in MGC total score.
The mean change of myasthenia gravis composite (MGC) total score, along with 2-sided 95% CI
Time frame: Weeks 2, 4, 8, and 12
Change and percentage change from baseline in MG-QoL15r scale.
The mean change of revised Myasthenia Gravis Quality of Life 15-Item Scale (MG-QoL 15r scale), along with 2-sided 95% CI
Time frame: Weeks 2, 4, 8, and 12]
Proportion of participants achieving MG-ADL response without rescue therapy.
MG-ADL response defined as a decrease of ≥3 points after treatment.
Time frame: Weeks 2, 4, 8, and 12
Proportion of participants achieving an improvement of 4, 5, 6, 7, and ≥8 points from baseline in QMG total score without rescue therapy.
Time frame: Weeks 2, 4, 8, and 12
Maximum Observed Serum Concentration (Cmax) of EA5
Time frame: Baseline up to Week 23
Area Under The Serum Concentration Versus Time Curve From Time Zero To The Time of The Last Quantifiable Concentration (AUC0-t) of EA5
Time frame: Baseline up to Week 23
Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-∞) of EA5
Time frame: Baseline up to Week 23
Minimum Steady-State Concentration (Cmin,ss) of EA5
Time frame: Baseline up to Week 23
Maximum Steady-State Concentration (Cmax,ss) of EA5
Time frame: Baseline up to Week 23
Average Steady-State Concentration (Cav.ss) of EA5
Time frame: Baseline up to Week 23
Steady-State Trough Concentration (Ctrough,ss) of EA5
Time frame: Baseline up to Week 23
Time to Maximum Steady-State Concentration (Tmax,ss) of EA5
Time frame: Baseline up to Week 23
Area Under the Concentration-Time Curve over One Dosing Interval at Steady State (AUC0-τ) of EA5
Time frame: Baseline up to Week 23
Degree of Fluctuation of EA5
Time frame: Baseline up to Week 23
Serum total complement hemolytic activity (CH50
Time frame: Baseline up to Week 23
Serum total C5 concentration
Time frame: Baseline up to Week 23
Serum free C5 concentration
Time frame: Baseline up to Week 23
Concentrations of plasma soluble C5b-9 (sC5b-9)
Concentration of plasma soluble Complement 5b-9 (sC5b-9)
Time frame: Baseline up to Week 23
Anti-acetylcholine receptor antibody (AChR-Ab) titer
Time frame: Baseline up to Week 23
Incidence of anti-drug antibodies (ADA) against the humanized monoclonal antibody EA5
Time frame: Baseline up to Week 23
Incidence of Incidence of neutralizing antibodies (NAb) against the humanized monoclonal antibody EA5
Time frame: Baseline up to Week 23
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