Study to Assess the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of GW003 in Patients With Breast Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Pegylated Recombinant Human G-CSF 100ug/kg 6 subjects (2 subjects per GW003 cohort) |
Biological: Pegylated Recombinant Human G-CSF
subcutaneous
|
| Experimental: GW003 300ug/kg 6-8 subjects |
Biological: GW003
subcutaneous
|
| Experimental: GW003 650ug/kg 6-8 subjects |
Biological: GW003
subcutaneous
|
| Experimental: GW003 850ug/kg 6-8 subjects |
Biological: GW003
subcutaneous
|
Outcome Measures
Primary Outcome Measures
- 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
- 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] [21days]
ANC will be detected pre-dose and 12h,24h,48h,72h,96h,120h,144h,168h,192h,216h,240h,264h,360h,408h,480h post-dose.
- CD34+ count [21days]
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.
- Time to absolute neutrophil count(ANC) recovery [21days]
The time of ANC of patients who experienced neutropenia after chemotherapy recover to normal levels.
- Incidence of severe neutropenia [21days]
The proportion of patients with grade 3 and 4 neutropenia as assessed by CTCAE v4.03.
- Duration of severe neutropenia(DSN) [21days]
Duration of grade 3 and 4 neutropenia as assessed by CTCAE v4.03.
- ANC nadir [21days]
The minimum value of ANC throughout the study period.
- Frequency of subjects with anti-GW003 antibody [21days]
Anti-GW003 antibody will be detected pre-dose and 21d.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- Jiangsu T-Mab Biopharma Co.,Ltd
Investigators
- Principal Investigator: Xichun Hu, Principal Investigator
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Tmab-GW003-NP-04