A Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Preliminary Efficacy and Pharmacokinetics of SCB-219M in the Patients With Chemotherapy-induced Thrombocytopenia
Overview
- Phase
- Phase 1
- Intervention
- Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein
- Conditions
- Chemotherapy-induced Thrombocytopenia (CIT)
- Sponsor
- Sichuan Clover Biopharmaceuticals, Inc.
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Dose escalation: Occurrence of DLT.
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
A Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Preliminary Efficacy and Pharmacokinetics of SCB-219M in the patients with chemotherapy-induced thrombocytopenia (CIT)
Detailed Description
The purpose of this trial is to evaluate the safety, tolerability, immunogenicity, and PK characteristics of single and multiple subcutaneous injections of SCB-219M for CIT, explore the MTD and BED, and preliminarily observe and evaluate efficacy. The trial is divided into a dose escalation phase (Ia) and an expansion phase (Ib).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: 18-75 years (inclusive), voluntary participation with signed informed consent and commitment to protocol-defined visits.
- •Body Weight: ≥40 kg.
- •Diagnosis: Histopathologically/cytopathologically confirmed malignant solid tumors or lymphoma.
- •Phase Ia: Platelet (PLT) \& Treatment Status:
- •PLT \<75×10⁹/L during prior chemotherapy cycle;
- •Receiving mono/combination chemotherapy (may include targeted/immunotherapy). 5.Phase Ib: Stratified Requirements:
- •Group A (1st-line CIT prophylaxis/therapy):
- •PLT \<50×10⁹/L, or
- •PLT 50-75×10⁹/L. • Group B (2nd-line CIT therapy/refractory cases): Second-line CIT treatment for refractory or treated CIT patients who failed first-line therapy (rhTPO/IL-11) with platelet count \<50×10⁹/L 6.Refractory/Treated CIT Definition:
- •Platelet count remains \<50×10⁹/L or increases by \<20×10⁹/L within 14 days after completing first-line CIT therapy (e.g., rhTPO or rhIL-11), with baseline PLT \<50×10⁹/L at enrollment.
Exclusion Criteria
- •Pregnancy/Lactation: Pregnant or breastfeeding females.
- •Hypersensitivity: Known allergy to protein-based drugs (e.g., recombinant proteins, mAbs) or excipients of the investigational product.
- •Active Infection: Acute infection requiring IV antibiotics without clinical control.
- •Prior Thrombopoietic Agents:
- •Group A: Use within specified windows pre-SCB-219M:
- •o Trilaciclib: ≤3 weeks
- •o Romiplostim: ≤2 weeks
- •o TPO-RAs (e.g., eltrombopag), rhTPO, IL-11, or platelet transfusion: ≤10 days
- •Group B: Use within:
- •o Romiplostim/rhTPO/IL-11: ≤7 days
Arms & Interventions
Dose Escalation
For single dose escalation, the dose level will be 2µg/kg -15 µg/kg.
Intervention: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein
Dose Expansion - Group A: First-line CIT treatment / Prophylactic administration for CIT (as needed)
The dose level is recommended to be the bioeffective dose obtained from dose escalation and administered once weekly (group A) , with a total of no more than 4 administrations within 70 days after the first dose.
Intervention: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein
Dose Expansion - Group B: Previously treated or refractory CIT
The dose level is recommended to be the bioeffective dose obtained from dose escalation and administered once weekly ( group B ), with a total of no more than 4 administrations within 70 days after the first dose.
Intervention: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein
Outcomes
Primary Outcomes
Dose escalation: Occurrence of DLT.
Time Frame: Occurrence of DLT from enrollment to day 21.
Occurrence of DLT
Dose escalation: Frequency of DLT.
Time Frame: Frequency of DLT from enrollment to day 21.
Frequency of DLT
Dose escalation and Dose expansion:Occurrence of AE.
Time Frame: 28 days after the last administration of SCB-219M
number, frequency,and charaterization of AEs
Secondary Outcomes
- Dose escalation: Cmax(up to 21 days after treatment)
- Dose escalation: Cmax/D(up to 21 days after treatment)
- Dose escalation: tmax(up to 21 days after treatment)
- Dose escalation: AUC0-24h(up to 21 days after treatment)
- Dose escalation: AUC0-last(up to 21 days after treatment)
- Dose escalation: AUC0-inf(up to 21 days after treatment)
- Dose escalation: t1/2(up to 21 days after treatment)
- Dose escalation: CL/F(up to 21 days after treatment)
- Dose escalation: Vz/F(up to 21 days after treatment)
- Dose escalation: λz(up to 21 days after treatment)
- Dose escalation: Preliminary efficacy assessment.The percentage of subjects requiring platelet infusion and the frequency of infusion during the DLT observation period.(up to 28 days after administration)
- Dose escalation: Preliminary efficacy assessment.(up to 28 days after administration)
- Dose expansion:：PK parameters of SCB-219M were established after repeated abdominal subcutaneous injections.(up to 168 hours after the last treatment)
- Dose expansion: Preliminary efficacy assessment.(Within 7, 14, 21, and 28 calendar days post-administration)
- Dose expansion: ：Platelet response onset time (days), duration of platelet effect maintenance (days), and overall response rate (%).(28 days after the last administration of SCB-219M)