This is a multicenter, open-label Phase1/2 study aimed at evaluating the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamics (PD), immunogenicity, and preliminary efficacy of ESG206. The study will be conducted in patients with primary immune thrombocytopenia.
Phase 1 is a dose escalation study, and Phase 2 is an extended cohort study, subjects will be treated with ESG206. In Phase 1\&2, the study includes Screening (no more than 28 days), Treatment (14 weeks), and the post-treatment follow-up (8 weeks), for those sufferring a treatment failure, the safe follow-up will be conducted 28 days after the last dose. And the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of ESG206 in primary ITP will be assessed in this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Qilu Hospital of Shandong University
Jinan, Shandong, China
RECRUITINGPercentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) were defined as: Any adverse event (AE) that happens after treatment initiation, or AE that was present at time of treatment initiation but worsened after treatment initiation, or AE that was present and resolved prior to treatment and reappeared after treatment initiation after the start of study drug through 28 days after the last dose of study drug or the last post-treatment follow-up. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events.
Time frame: Up to 24 weeks.
Confirmed response rate
Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of: Rescue treatment for ≥4 weeks prior to the assessment of the platelet count, and New immune thrombocytopenia (ITP) treatment before reaching a confirmed response.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
AUC0-inf
Area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity
Time frame: up to Week 25
Cmax
Maximum observed plasma concentration
Time frame: up to Week 25
Tmax
Time to maximum plasma concentration
Time frame: up to Week 25
T1/2
Half-life
Time frame: up to Week 25
Response rate at each timepoint
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Administered via intravenous (IV) infusion
Percentage of participants with a platelet count of at least 50 G/L in the absence of rescue treatment/new ITP treatment.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Complete Response rate at each timepoint
Percentage of participants with a platelet count of at least 100 G/L in the absence of rescue treatment/new ITP treatment.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Best Response rate at each timepoint
Percentage of participants with Response or Complete Response in the absence of rescue treatment/new ITP treatment.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Time to confirmed response
Time from the first administration of ESG206 to the first assessment in the first sequence of two (or more) platelet assessments meeting the criteria of a confirmed response as defined by the primary endpoint.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Time to complete response
Time from the first administration of ESG206 to the first assessment meeting the criteria of a complete response.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Time to treatment failure
Time from the first administration until platelet count below 30 G/L, need for a rescue treatment or start of a new therapy or death.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Duration of response
Time from achievement of response to loss of response
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Duration of complete response
Time from achievement of complete response to loss of complete response.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Percentage of participants receiving rescue treatment
Assess the need of rescue treatment by percentage.
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Change from baseline in absolute number of CD19+ B cell counts
Post baseline absolute number of CD19+ B cell counts compare with baseline
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Change from baseline in absolute number of CD20+ B cell counts
Post baseline absolute number of CD20+ B cell counts compare with baseline
Time frame: Between Week 1 Day 1 and Week 25 Day 1
Incidence of anti-drug antibodies in serum (ADA assay) over time
Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assess the immunogenicity of ESG206
Time frame: Between Week 1 Day 1 and Week 25 Day 1