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

Phase 1

Active, not recruiting

• Conditions: Chemotherapy-induced Thrombocytopenia (CIT)
• Interventions: Biological: Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein

• Registration Number: NCT05426369
• Lead Sponsor: Sichuan Clover Biopharmaceuticals, Inc.

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).

Study Timeline

• Study First Submitted: 2022-05-10
• Study Start: 2022-06-14
• Study First Submitted QC: 2022-06-15
• Study First Posted: 2022-06-22
• Status Verified: 2025-07
• Primary Completion: 2025-07-02
• Last Update Submitted: 2025-07-28
• Last Update Posted: 2025-07-31
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 36

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:

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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):

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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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein	For single dose escalation, the dose level will be 2µg/kg -15 µg/kg.
Dose Expansion - Group A: First-line CIT treatment / Prophylactic administration for CIT (as needed)	Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein	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.
Dose Expansion - Group B: Previously treated or refractory CIT	Recombinant Human Tumor Necrosis Factor Receptor II -Fc-TPO Mimetic Peptide Fusion Protein	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China