A Clinical Trial Evaluating SCB-219M in in Chemotherapy-induced Thrombocytopenia (CIT)

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Chemotherapy-induced Thrombocytopenia (CIT)
• Intervention / Treatment: Biological: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein

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).

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-75 years (inclusive), voluntary participation with signed informed consent and commitment to protocol-defined visits.
2. Body Weight: ≥40 kg.
3. Diagnosis: Histopathologically/cytopathologically confirmed malignant solid tumors or lymphoma.
4. Phase Ia: Platelet (PLT) & Treatment Status:

1. PLT <75×10⁹/L during prior chemotherapy cycle;

2. Receiving mono/combination chemotherapy (may include targeted/immunotherapy). 5.Phase Ib: Stratified Requirements:

   • Group A (1st-line CIT prophylaxis/therapy):

1. PLT <50×10⁹/L, or

2. 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.

     7.Toxicity Resolution: Prior anti-tumor toxicity ≤ Grade 2 (CTCAE v5.0) at enrollment (alopecia/vitiligo/subjective symptoms excluded).

     8.ECOG PS: 0-2. 9.Life Expectancy: ≥3 months (investigator-assessed). 10.Baseline Laboratory (Pre-dose):

   • a) Creatinine ≤1.5×ULN; CrCl >40 mL/min;
   • b) PT/APTT/INR 80-120% of normal range;
   • c) ANC ≥1.5×10⁹/L;
   • d) Hemoglobin ≥70 g/L;
   • e) Albumin ≥25 g/L. 11.Liver Function:
   • a) ALT/AST ≤3×ULN (≤5×ULN if liver metastasis);

   • b) Total bilirubin ≤2.0×ULN (Gilbert's syndrome/asymptomatic cholelithiasis exempted).

     12.Contraception:

   • Fertile subjects must use ≥1 method:

     o Absolute abstinence;

     • Double-barrier (condom + spermicidal diaphragm);
     • IUD/hormonal contraceptives (oral/implant/patch/injection);
     • Hysterectomy/bilateral salpingectomy/tubal ligation (females or partners);
     • Vasectomy/azoospermia (males or partners).
   • Females: Negative serum β-HCG within 28 days;
   • Males: No sperm donation from first dose to 180 days post-last dose.

Exclusion Criteria:

1. Pregnancy/Lactation: Pregnant or breastfeeding females.
2. Hypersensitivity: Known allergy to protein-based drugs (e.g., recombinant proteins, mAbs) or excipients of the investigational product.
3. Active Infection: Acute infection requiring IV antibiotics without clinical control.

4. 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

   o TPO-RAs/platelet transfusion: ≤3 days

5. Anticoagulant Use: Anticoagulants/antiplatelet drugs ≤5 half-lives pre-dose or needed during study (aspirin washout ≥7 days).
6. Non-Chemotherapy Thrombocytopenia (within 6 months/unresolved):

1) Clinically significant non-chemotherapy-induced thrombocytopenia (e.g., EDTA-dependent pseudothrombocytopenia) 2) Hematologic malignancies (excluding lymphoma; e.g., leukemia) 3) Multiple myeloma 7.Bleeding Events (within 2 weeks pre-screening):

• Group A: ≥Grade 2 (WHO Bleeding Scale)

• Group B: ≥Grade 3 (WHO Bleeding Scale) 8.Non-CIT Thrombocytopenia Etiologies: 1) Primary immune thrombocytopenia (pITP) 2) Bone marrow failure (e.g., aplastic anemia, Fanconi anemia) 3) Myeloproliferative disorders/MDS 4) Hypersplenism secondary to hematologic/autoimmune diseases 9.Splenectomy/Splenic Effects: Splenic metastasis affecting hematopoiesis; splenectomy/splenic artery embolization ≤12 weeks pre-enrollment.

  10.Uncontrolled Cardiovascular Disease:

• NYHA Class III/IV heart failure
• Pro-thrombotic conditions (e.g., atrial fibrillation, unstable angina)
• QTc >470 ms (>480 ms with bundle branch block)
• Myocardial infarction ≤6 months (Note: Pacemaker/ICD users with normal function eligible) 11.Thrombotic/Coagulation Disorders:
• Coagulopathies
• Arterial/venous thrombosis ≤3 months (excluding PICC-related thrombosis)

• Transient ischemic attack ≤3 months 12.Major Procedures/Radiotherapy: Major surgery/radiotherapy ≤4 weeks pre-dose (except toxicity ≤Grade 2 [CTCAE v5.0], alopecia/vitiligo permitted).

  13.CNS Metastases: Active/untreated CNS or leptomeningeal metastases (asymptomatic brain metastases allowed).

  14.Uncontrolled Hypertension: Resting SBP ≥160 mmHg and/or DBP ≥100 mmHg (two measurements, 2h apart).

  15.Active Infections:

• HIV seropositivity
• Active HBV (HBsAg+ andHBV DNA >LLOQ)

• Active HCV (anti-HCV+ andHCV RNA >LLOQ) 16.Live Vaccines: Live attenuated vaccines ≤4 weeks pre-dose (COVID-19 vaccines permitted except Ad5-vectored type [requires investigator assessment]).

  17.Concurrent Clinical Trials: Participation in other drug/device trials ≤4 weeks pre-dose or planned during study.

  18.Investigator's Discretion: Poor compliance or other factors deemed unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; For single dose escalation, the dose level will be 2µg/kg -15 µg/kg.	Biological: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein; Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein for injection (Strength: 1 mg/ml, 0.5ml/vial)
Experimental: 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.	Biological: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein; Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein for injection (Strength: 1 mg/ml, 0.5ml/vial)
Experimental: 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.	Biological: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein; Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein for injection (Strength: 1 mg/ml, 0.5ml/vial)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation: Occurrence of DLT.	Occurrence of DLT	Occurrence of DLT from enrollment to day 21.
Dose escalation: Frequency of DLT.	Frequency of DLT	Frequency of DLT from enrollment to day 21.
Dose escalation and Dose expansion:Occurrence of AE.	number, frequency,and charaterization of AEs	28 days after the last administration of SCB-219M

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation: Cmax	Cmax : Maximum serum concentration	up to 21 days after treatment
Dose escalation: Cmax/D	Cmax/D :Dose normalized Cmax	up to 21 days after treatment
Dose escalation: tmax	tmax : Time to Cmax	up to 21 days after treatment
Dose escalation: AUC0-24h	AUC0-24h: Area under the serum concentration-time curve from 0 h to 24 h	up to 21 days after treatment
Dose escalation: AUC0-last	AUC0-last :Area under the serum concentration-time curve from 0 h on Day 1 to the last time point with a quantifiable concentration	up to 21 days after treatment
Dose escalation: AUC0-inf	AUC0-inf : Area under the serum concentration-time curve from 0 h extrapolated to infinity	up to 21 days after treatment
Dose escalation: t1/2	t1/2 : Apparent half-life	up to 21 days after treatment
Dose escalation: CL/F	CL/F: Systemic clearance	up to 21 days after treatment
Dose escalation: Vz/F	Vz/F: Volume of distribution	up to 21 days after treatment
Dose escalation: λz	λz: Elimination rate constant	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.	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.	Duration of PLT count ≥50×10^9/L and percentage of subjects during the DLT observation period.	up to 28 days after administration
Dose escalation: Preliminary efficacy assessment.	Duration of PLT count ≥75×10^9/L and percentage of subjects during the DLT observation period.	up to 28 days after administration
Dose escalation: Preliminary efficacy assessment.	Duration of PLT count ≥100×10^9/L and percentage of subjects during the DLT observation period	up to 28 days after administration
Dose expansion:：PK parameters of SCB-219M were established after repeated abdominal subcutaneous injections.	The PK parameters include: C₀, Cmax/D, Css_min, Cmax_ss, Cav_ss, Rac, tmax, AUC₀-last, AUC₀-inf, AUCss, DF, MRT, t₁/₂, etc.	up to 168 hours after the last treatment
Dose expansion: Preliminary efficacy assessment.	Incidence of grade 2/3/4 thrombocytopenia (CTCAE version 5.0).	28 days after the last administration of SCB-219M
Dose expansion: Preliminary efficacy assessment.	Percentage of subjects requiring platelet transfusions and number of transfusions within 7, 14, 21, and 28 days post-dose	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 (%).	Key efficacy endpoints per protocol: Time (days) to first achievement of platelet counts ≥50×10⁹/L, ≥75×10⁹/L, and ≥100×10⁹/L post-dose ;;; Duration (days) of sustained platelet count maintenance at or above prespecified thresholds (≥50×10⁹/L, ≥75×10⁹/L, ≥100×10⁹/L);; Responder rate (%) , defined as the proportion of subjects achieving predefined platelet count thresholds.	28 days after the last administration of SCB-219M

Collaborators and Investigators

• Sponsor: Sichuan Clover Biopharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Actual): July 2, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: CLO-SCB-219M-CHN-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No