Safety and Pharmacokinetic(PK) Study of GW003 to Metastatic Tumors

Chemotherapy-induced Neutropenia Clinical Trial

Official title:

A Single-center, Uncontrolled, Open, Phase 1 Study of Recombinant(Expressed by Pichia Pastoris) Human Serum Albumin/Human Granulocyte-Colony Stimulating Factor(I)Fusion Protein For Injection(GW003)to Metastatic Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02156388
• Other study ID #: Tmab-GW003-NP-01
• Status: Completed
• Phase: Phase 1
• First received: May 28, 2014
• Last updated: February 22, 2016
• Start date: August 2013
• Est. completion date: December 2015

Study information

• Verified date: February 2016
• Source: Jiangsu T-Mab Biopharma Co.,Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is designed to access the safety, tolerance and Pharmacokinetic/Pharmacodynamic(PK/PD) of single subcutaneous(SC) injection of GW003 in patients with metastatic tumors.

Description:

So far, granulocyte colony stimulating factor (G-CSF) is still currently the only effective and security therapy drug for neutropenia caused by cancer chemotherapy. At present, the widely used G-CSF products are of such short-acting G-CSF product in China. However, there existed some shortcoming about short-acting G-CSF, such as shorter half-life, continuous monitoring of the patient's blood neutrophil count and so on.

Nowadays,long-acting G-CSF product,such as Neulasta®, has become the mainstream of the foreign G-CSF market for its superiority of long half-life and absence of monitoring of the patient's blood neutrophil count. The new drug Recombinant(Expressed by Pichia pastoris) Human Serum Albumin/Human Granulocyte-Colony Stimulating Factor(I)Fusion Protein(GW003) is a long-acting G-CSF.Preclinical studies have shown that GW003 has accelerated neutrophil recovery and can shorten the duration of neutropenia symptoms, also reduce its extent, therefore minimize the likelihood of serious infections, reflecting a better efficacy and more long half-life.

Phase I was performed as two parts, Ia and Ib. Ia was a sequential dose escalation to observe the dose-limiting toxicity(DLT) and Maximum Tolerated Dose of GW003 given subcutaneously to patients without receiving chemotherapy,6 dose cohorts(50、150、300、400、500 and 600μg/kg) with 2-3 subjects in the 50、150μg/kg cohorts and 3-6 subjects（depend on the Dose-limiting toxicity） in the 300、400、500 and 600μg/kg cohorts, to evaluate safety and pharmacokinetics prior to the Ⅰb.

Ib proposed two arms (150 and 300μg/kg；n=6-8/arm), and to determine whether to continue to increase other dose arm based on the safety and efficacy assessment. Subjects need to receive two cycles treatment of AT chemotherapy. In cycle 1, subjects received AT chemotherapy only; in cycle 2, subjects were administered subcutaneously GW003 24 hours after chemotherapy drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients with pathologically and/or cytologically-confirmed malignant tumor (phase Ia)

2. Breast-cancer or NSCLC patients are suitable for chemotherapy regimen of receiving docetaxel plus adriamycin and could finish two-cycles adjuvant chemotherapy on schedule

3. 18 years to 65years

4. Patients with Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1 and living at least 6 months

5. No main organ dysfunction, adequate cardiac,hepatic,renal and bone marrow function

6. Adequate hematologic function (value in center laboratory as the standard); white blood cell count (WBC)=4.0×109/L neutrophil count (ANC)=1.5×109/L; platelet count (PLT)=100×109/L; hemoglobin (HGB)=lOO g/L.

7. Adequate hepatic and renal function(value in center laboratory as the standard):

8. Women of childbearing age need to pregnancy test Prior to receive therapy and agree to use effective contraception throughout the study

9. Subjects, who are willing to follow the study protocol and provide written informed consent voluntarily, have understood the purpose and procedures and could follow requirements of the study

Exclusion Criteria:

1. History of cardiopathy or with signs and symptoms

2. History of bone marrow transplant and/or stem cell transplant

3. Patients with acute infection, systemic anti-infection treatment within 72 hours of study

4. Prior participated in drug therapy, radiotherapy or surgery and other clinical trials within 4 weeks

5. Prior use of recombinant human G-CSF(rhG-CSF)?PEG-rhG-CSF or erythropoietin within 4 weeks of study

6. Patients with history of primary myeloid malignancy or myelodysplasia

7. Known hypersensitivity to test drugs, rhG-CSF or any other biologicals

8. Pregnant female or nursing mother

9. Known HIV positive or active hepatitis

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy-induced Neutropenia
• Metastatic Tumors
• Neoplasm Metastasis
• Neutropenia

Intervention

Biological:
• GW003
freeze-dried powder;single SC injection

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

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	Number of participants with adverse event	To evaluate the safety and tolerance of single SC injection of GW003 to Metastatic Tumors.	Ia:up to 4weeks;Ib: up to 10weeks	Yes
Secondary	Duration of severe neutropenia(DSN)		Ia: up to 3weeks;Ib: up to 6weeks.	No
Secondary	Anti-GW003 antibody	Ia:anti-GW003 antibody was detected pre-dose and when visit,if there exist positive anti-GW003 antibody, another detected should be conducted 6 months after the trial.; Ib:anti-GW003 antibody was detected pre-dose ,after cycle 2 chemotherapy and when visit,if there exist positive anti-GW003 antibody, another detected should be conducted 6 months after the trial.	Ia: up to 28weeks;Ib: up to 34weeks.	No
Secondary	half-life(consists of distribution half-life [t1/2a] and elimination half-life [t1/2ß])		Pre-dose?0.5h?1h?2h?3h?6h?9h?12h?24h?48h?72h?96h?120h?144h and 168h post-dose	No
Secondary	area under the concentration-time curve (AUC)		Pre-dose?0.5h?1h?2h?3h?6h?9h?12h?24h?48h?72h?96h?120h?144h and 168h post-dose	No