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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chemotherapy-induced Neutropenia
• Intervention / Treatment: Biological: Pegylated Recombinant Human G-CSF; Biological: GW003

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jiangsu T-Mab Biopharma Co.,Ltd
• Investigators: Principal Investigator: Xichun Hu, Principal Investigator

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Breast Cancer; Neutropenia; GW003
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia
• Other Study ID Numbers: Tmab-GW003-NP-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided