A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Human Serum Albumin/Human Granulocyte-Colony Stimulating Factor(I) Fusion Protein for Injection (GW003) in Patients With Breast Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to GW003 as assessed by CTCAE v4.03
研究概览
简要总结
The purpose of the present trial is to evaluate the safety, tolerability and pharmacokinetics(PK)/pharmacodynamics(PD) of single subcutaneous injection of GW003 in breast cancer patients. Moreover, the efficacy will be assessed preliminary.
详细描述
This is an single-center, open-label, randomized, active-controlled phase I study evaluating tolerability and pharmacokinetics/pharmacodynamics of single subcutaneous injections of GW003 in the breast cancer patients.GW003 is recombinant human serum albumin/human granulocyte-colony stimulating factor(I)fusion protein .It is a long-acting G-CSF(Granulocyte-Colony Stimulating Factor). In this study, participants will be administered a single dose of GW003. Every subject will only accept one dose. In addition to tolerability and safety, pharmacokinetics/pharmacodynamics, preliminary efficacy and immunogenicity of GW003 will be evaluated as well.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years to 70 years, female
- •Patients with histologically-confirmed breast cancer and plan to accept adjuvant chemotherapy(epirubicin plus cyclophosphamide)
- •Have an Eastern Cooperative Oncology Group(ECOG) performance status≤2
- •Have no clinically significant impairment in cardiac, liver and kidney
- •Adequate hematologic, hepatic and renal function which should meet the following requirements:
- •Absolute neutrophil count(ANC)≥1.5 x 10^9/L
- •Blood platelet(PLT)≥100 x 10^9/L
- •Serum creatinine(sCr)≤1.5 times the upper limit of normal(ULN)
- •Total bilirubin(TBIL)≤1.5×ULN
- •Aspartate aminotransferase(AST) /serum glutamic-oxaloacetic transaminase(SGOT) and/or alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase(SGPT) ≤ 2.5 x ULN
- •Hemoglobin(Hb)>9 g/dL
- •Alkaline phosphatase(ALP)≤1.5×ULN
- •Expected to comply with protocol
- •With urine human chorionic gonadotropin (hCG) negative
- •Signed informed consent
排除标准
- •With acute infection
- •With history of bone marrow transplant and/or stem cell transplant
- •With primary hematological diseases, such as myelodysplastic syndromes, aplastic anemia, sickle cell anemia
- •Received surgery within 3 weeks before chemotherapy
- •Received G-CSF within 4 weeks before involved in this study
- •Females who are pregnant or lactating
- •Participated in other clinical trials at the same time or within 4 weeks before screening
- •Known allergy to chemotherapy drugs,recombinant human granulocyte-colony stimulating factor rh(rhG-CSF) or any other biological products
- •With cacoethic addiction such as drug abuse or alcoholism
- •With other cases which is not suitable for this study judged by investigator
研究组 & 干预措施
Pegylated Recombinant Human G-CSF
100ug/kg 6 subjects (2 subjects per GW003 cohort)
干预措施: Pegylated Recombinant Human G-CSF (Biological)
GW003 300ug/kg
6-8 subjects
干预措施: GW003 (Biological)
GW003 850ug/kg
6-8 subjects
干预措施: GW003 (Biological)
GW003 650ug/kg
6-8 subjects
干预措施: GW003 (Biological)
结局指标
主要结局
Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to GW003 as assessed by CTCAE v4.03
时间窗: 21days
次要结局
- Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration [AUC0-t](21days)
- Terminal elimination half-life[T1/2](21days)
- CD34+ count(21days)
- Time to reach the maximum observed plasma concentration [Tmax](21days)
- Incidence of severe neutropenia(21days)
- Frequency of subjects with anti-GW003 antibody(21days)
- Area under the plasma concentration-time curve from time zero to infinity[AUC0-inf](21days)
- Time to absolute neutrophil count(ANC) recovery(21days)
- Absolute neutrophil count[ANC](21days)
- Duration of severe neutropenia(DSN)(21days)
- ANC nadir(21days)
- Maximum observed maximum plasma concentration [Cmax](21days)