This is a multicenter, open-label, Phase Ib clinical trial designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of the humanized monoclonal antibody EA5 in adult patients with paroxysmal nocturnal hemoglobinuria (PNH).
This is a multicenter, open-label, Phase Ib clinical trial designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of the humanized monoclonal antibody EA5 in adult patients with paroxysmal nocturnal hemoglobinuria (PNH). The study plans to enroll 24-26 PNH patients. The primary objective is to assess the incidence and severity of adverse events (AEs) from baseline to Week 14.The treatment period is divided into a Loading Phase (Day 1 to Day 14) and a Maintenance Phase (Day 15 to Day 85). During the maintenance phase, patients will be assigned to one of three dose cohorts: Cohort 1/Cohort 1' (900 mg, IV, Q4W), Cohort 2/Cohort 2' (1200 mg, IV, Q4W), and Cohort 3 (1400 mg, IV, Q4W). Cohorts 1-3 are for patients previously naive to complement inhibitor therapy, while Cohorts 1'-2' are for patients recently naive to complement inhibitor therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
All treatments were given as IV infusions.
The Institute of Hematology & Blood Diseases Hospital (Chinese Academy of Medical Sciences)
Tianjin, Tianjin Municipality, China
RECRUITINGThe First Affiliated Hospital, Zhejiang University School of Medicine, Chengzhan Campus
Hangzhou, Zhejiang, China
RECRUITINGNumber of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Baseline up to Week 14
Maximum Observed Serum Concentration (Cmax) of EA5
Blood samples were collected for analysis of Cmax
Time frame: Baseline up to Week 14
Time To Maximum Observed Serum Concentration (Tmax) of EA5
Blood samples were collected for analysis of Tmax
Time frame: Baseline up to Week 14
Area Under The Serum Concentration Versus Time Curve From Time Zero To The Time of The Last Quantifiable Concentration (AUC0-t) of EA5
Blood samples were collected for analysis of AUC0-t
Time frame: Baseline up to Week 14
Area Under The Serum Concentration Versus Time Curve From Time Zero (Dosing) To Infinity (AUCinf) of EA5
Blood samples were collected for analysis of AUCinf
Time frame: Baseline up to Week 14
Terminal Elimination Rate Constant (λz) of Serum EA5
Blood samples were collected for analysis of λz
Time frame: Baseline up to Week 14
Terminal Elimination Half-life (t½) of Serum EA5
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Blood samples were collected for analysis of t½
Time frame: Baseline up to Week 14
Total Clearance (CL) of EA5
Blood samples were collected for analysis of CL
Time frame: Baseline up to Week 14
Percent Change From Baseline in Free Complement Component 5 (C5)
Blood samples were collected for analysis of free C5 concentrations.
Time frame: Baseline up to Week 14
Percent Change From Baseline in Total Complement C5
Blood samples were collected for analysis of total C5 concentrations.
Time frame: Baseline up to Week 14
Percent Change From Baseline in determination of terminal complement activity in serum
Blood samples were collected for analysis of determination of terminal complement activity
Time frame: Baseline up to Week 14
Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Blood samples were collected to evaluate antibody response through development of ADAs.
Time frame: Baseline up to Week 14