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

Chemotherapy-induced Neutropenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02725606
• Other study ID #: Tmab-GW003-NP-04
• Status: Recruiting
• Phase: Phase 1
• First received: March 24, 2016
• Last updated: August 15, 2017
• Start date: March 2016
• Est. completion date: September 2017

Study information

• Verified date: January 2017
• Source: Jiangsu T-Mab Biopharma Co.,Ltd
• Contact: Xichun Hu
• Email: xchu2009[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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:

1. Absolute neutrophil count(ANC)=1.5 x 10^9/L

2. Blood platelet(PLT)=100 x 10^9/L

3. Serum creatinine(sCr)=1.5 times the upper limit of normal(ULN)

4. Total bilirubin(TBIL)=1.5×ULN

5. Aspartate aminotransferase(AST) /serum glutamic-oxaloacetic transaminase(SGOT) and/or alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase(SGPT) = 2.5 x ULN

6. Hemoglobin(Hb)>9 g/dL

7. 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

Related Conditions & MeSH terms

• Breast Neoplasms
• Chemotherapy-induced Neutropenia
• Neutropenia

Intervention

Biological:
• Pegylated Recombinant Human G-CSF
subcutaneous
• GW003
subcutaneous

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu T-Mab Biopharma Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to GW003 as assessed by CTCAE v4.03		21days
Secondary	Maximum observed maximum plasma concentration [Cmax]		21days
Secondary	Time to reach the maximum observed plasma concentration [Tmax]		21days
Secondary	Area under the plasma concentration-time curve from time zero to infinity[AUC0-inf]		21days
Secondary	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
Secondary	Terminal elimination half-life[T1/2]		21days
Secondary	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
Secondary	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
Secondary	Time to absolute neutrophil count(ANC) recovery	The time of ANC of patients who experienced neutropenia after chemotherapy recover to normal levels.	21days
Secondary	Incidence of severe neutropenia	The proportion of patients with grade 3 and 4 neutropenia as assessed by CTCAE v4.03.	21days
Secondary	Duration of severe neutropenia(DSN)	Duration of grade 3 and 4 neutropenia as assessed by CTCAE v4.03.	21days
Secondary	ANC nadir	The minimum value of ANC throughout the study period.	21days
Secondary	Frequency of subjects with anti-GW003 antibody	Anti-GW003 antibody will be detected pre-dose and 21d.	21days