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

Phase 1

• Conditions: Chemotherapy-induced Neutropenia
• Interventions: Biological: GW003; Biological: Pegylated Recombinant Human G-CSF

• Registration Number: NCT02725606
• Lead Sponsor: Jiangsu T-Mab Biopharma Co.,Ltd

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.

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 Timeline

• Study Start: 2016-03
• Study First Submitted: 2016-03-24
• Study First Submitted QC: 2016-03-31
• Study First Posted: 2016-04-01
• Status Verified: 2017-01
• Last Update Submitted: 2017-08-15
• Last Update Posted: 2017-08-18
• Primary Completion: 2017-09
• Study Completion: 2017-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GW003 300ug/kg	GW003	6-8 subjects
Pegylated Recombinant Human G-CSF	Pegylated Recombinant Human G-CSF	100ug/kg 6 subjects (2 subjects per GW003 cohort)
GW003 650ug/kg	GW003	6-8 subjects
GW003 850ug/kg	GW003	6-8 subjects

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Time to reach the maximum observed plasma concentration [Tmax]	21days
Incidence of severe neutropenia	21days	The proportion of patients with grade 3 and 4 neutropenia as assessed by CTCAE v4.03.
Frequency of subjects with anti-GW003 antibody	21days	Anti-GW003 antibody will be detected pre-dose and 21d.
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	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.
Area under the plasma concentration-time curve from time zero to infinity[AUC0-inf]	21days
Time to absolute neutrophil count(ANC) recovery	21days	The time of ANC of patients who experienced neutropenia after chemotherapy recover to normal levels.
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.
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.
Maximum observed maximum plasma concentration [Cmax]	21days

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China