Study to Assess the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of GW003 in Patients With Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chemotherapy-induced Neutropenia

Intervention / Treatment
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* Biological: Pegylated Recombinant Human G-CSF
* Biological: GW003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pegylated Recombinant Human G-CSF<br>100ug/kg 6 subjects (2 subjects per GW003 cohort) | Biological: Pegylated Recombinant Human G-CSF<br>* subcutaneous<br>|
| Experimental: GW003 300ug/kg<br>6-8 subjects | Biological: GW003<br>* subcutaneous<br>|
| Experimental: GW003 650ug/kg<br>6-8 subjects | Biological: GW003<br>* subcutaneous<br>|
| Experimental: GW003 850ug/kg<br>6-8 subjects | Biological: GW003<br>* subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to GW003 as assessed by CTCAE v4.03 |  | 21days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed maximum plasma concentration [Cmax] |  | 21days | 
| Time to reach the maximum observed plasma concentration [Tmax] |  | 21days | 
| Area under the plasma concentration-time curve from time zero to infinity[AUC0-inf] |  | 21days | 
| 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 | 
| Absolute neutrophil count[ANC] | ANC will be detected pre-dose and 12h,24h,48h,72h,96h,120h,144h,168h,192h,216h,240h,264h,360h,408h,480h post-dose. | 21days | 
| CD34+ count | CD34+ count will be detected pre-dose and 12h,24h,48h,72h,96h,120h,144h,168h,192h,216h,240h,264h,360h,408h,480h post-dose. | 21days | 
| Time to absolute neutrophil count(ANC) recovery | The time of ANC of patients who experienced neutropenia after chemotherapy recover to normal levels. | 21days | 
| Incidence of severe neutropenia | The proportion of patients with grade 3 and 4 neutropenia as assessed by CTCAE v4.03. | 21days | 
| Duration of severe neutropenia(DSN) | Duration of grade 3 and 4 neutropenia as assessed by CTCAE v4.03. | 21days | 
| ANC nadir | The minimum value of ANC throughout the study period. | 21days | 
| Frequency of subjects with anti-GW003 antibody | Anti-GW003 antibody will be detected pre-dose and 21d. | 21days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neutropenia, Breast Cancer, GW003