Trial to Compare the Efficacy and Safety of F-627 and GRAN®

Study Overview
=================
Brief Summary
-----------------
A Phase III, Multi-Center, Randomized, Open-Label, Active-Controlled Trial to Compare the Efficacy and Safety of Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein (F-627) and Recombinant Human Granulocyte Colony Stimulating Factor (GRAN®) in the Prophylactic Treatment for Chemotherapy-Induced Neutropenia

Detailed Description
-----------------
Protocol Number: SP11631 Study Stage: Phase III Study Population Female patients with breast cancer will be enrolled to receive at least 4 cycles of EC chemotherapy, that is: epirubicin 100 mg/m2 and cyclophosphamide 600 mg/m2. Study Design: A multi-center, randomized, open-label, active-controlled phase III clinical trial Site Number: 14 sites(planned) , 12 sites(actual) Subject Number: 240

Official Title
-----------------
A Phase III, Multi-Center, Randomized, Open-Label, Active-Controlled Trial to Compare the Efficacy and Safety of F-627 and GRAN® in the Prophylactic Treatment for Chemotherapy-Induced Neutropenia

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Biological: F-627


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing to sign the informed consent form and able to comply with protocol requirements; 18-75 years old; Female postoperative patients with breast cancer who require adjuvant chemotherapy, and are planned to receive at least 4 cycles of EC chemotherapy, namely epirubicin 100 mg/m2 + cyclophosphamide 600 mg/m2; ECOG performance status ≤ 2; Absolute neutrophil count (ANC) ≥ 2.0 × 109/L, hemoglobin (Hb) ≥ 11.0 g/dL, and platelet (PLT) ≥ 100 × 109/L prior to enrollment; Hepatic and renal functions: Total bilirubin ≤ 1.5 × ULN, ALT and AST ≤ 2.5 × ULN, serum creatinine ≤ 1.5 × ULN; Left ventricular ejection fraction > 50%; Women without child-bearing potential, i.e., women who have had menopause for at least 1 year or who have undergone sterilization (bilateral tubal ligation, double oophorectomy or hysterectomy); patients with child-bearing potential should agree to take appropriate contraceptive measures, including condoms, spermicidal condoms, foams, gels, contraceptive barrier, intrauterine devices (IUD), and contraceptives (oral or injection), starting from 1 month before the start of the study until 30 days after the end of the study. Exclusion Criteria: Radiation therapy within 4 weeks prior to enrollment; Patients with breast cancer who have received neoadjuvant chemotherapy before surgery; Prior bone marrow or stem cell transplant; With other malignant tumors other than breast cancer; Patients who have received a treatment with recombinant human granulocyte colony stimulating factor within 6 weeks prior to randomization; Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, ECG or other approaches; With any disease that may cause splenomegaly; With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C; Women in pregnancy or breastfeeding; Known HIV positive or AIDS; With active tuberculosis (TB); history of TB exposure, unless negative for tuberculin test; TB patients undergoing treatment; or suspected TB evaluated by chest x-ray; With sickle cell anemia; With alcohol or drug abuse that may affect the compliance with the study; With known hypersensitivity to granulocyte colony stimulating factor or excipients; Have received any other investigational drug within 1 month or 5 half-lives of the investigational drugs prior to enrollment (whichever is longer); Patients with diseases or symptoms unsuitable for participating in the trial. For example, the study drugs may compromise the health of the patient or the assessment of adverse events may be affected.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F-627<br>Subjects will receive F-627 (20 mg/dose, s.c.) on day 3 of each cycle, i.e., 48 ±4 h after the start of chemotherapy. | Biological: F-627<br>* Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein<br>|
| Active Comparator: GRAN®<br>Subjects will receive GRAN® [5 μg/kg/day, s.c., once daily (± 4 h) up to 2 weeks or until neutrophil count returns to 5.0 ×109/L] on day 3 of each cycle, i.e., 48 ±4 h after the start of chemotherapy. | Biological: F-627<br>* Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of F-627 versus GRAN® in the first cycle of prophylactic treatment in subjects with breast cancer receiving chemotherapy, as assessed by the number of days in which ANC < 1.0 × 109/L in cycle 1 | The primary endpoint is the duration (days) of grade 3 or 4 (moderate and severe) neutropenia in cycle 1, that is, the number of days in which ANC < 1.0 × 109/L in cycle 1. | At the end of cycle 1（each cycle is 21 days）. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of grade 3 or 4 neutropenia as assessed by ANC（ANC < 1.0 × 109/L and ANC < 0.5 × 109/L, respectively） | The incidence rate of grade 3 or 4 neutropenia (ANC < 1.0 × 109/L and ANC< 0.5 × 109/L, respectively) | through study completion, an average of 21 days. | 
| durations (days) of grade 3 or 4 neutropenia as assessed by ANC（ANC < 1.0 × 109/L and ANC < 0.5 × 109/L, respectively） | The durations (days) of grade 3 or 4 neutropenia (ANC < 1.0 × 109/L and < 0.5 × 109/L, respectively) | in cycles 2-4, at the end of cycle 4（each cycle is 21 days.） | 
| incidence and duration (days) of grade 4 neutropenia are all as assessed by ANC（ANC < 0.5 × 109/L） | The incidence and duration (days) of grade 4 neutropenia (ANC < 0.5 × 109/L) | through study completion, an average of 21 days. | 
| overall duration (days) of grade 3 or 4 neutropenia as assessed by ANC（ANC < 1.0 × 109/L and ANC < 0.5 ×109/L, respectively） | The overall duration (days) of grade 3 or 4 neutropenia (ANC < 1.0 × 109/L and ANC< 0.5 × 109/L, respectively) | through study completion, in overall 4 cycles（each cycle is 21 days）. | 
| The incidence and duration (days) of grade 2 or above neutropenia are all assessed by ANC (ANC < 1.5 × 109/L) | The incidence and duration (days) of grade 2 or above neutropenia (ANC < 1.5 × 109/L) in each cycle. | through study completion, an average of 21 days. | 
| Incidence of febrile neutropenia (FN) (defined as ANC < 1.0×109/L; a single measurement of body temperature > 38.3°C or a temperature ≥ 38.0 °C sustained over 1 h) | Incidence rate of febrile neutropenia (FN) (defined as ANC < 1.0×109/L; a single measurement of body temperature > 38.3 °C or a temperature ≥ 38.0 °C sustained over 1 hr) | 8 months | 
| ANC nadir | The time (days) of ANC nadir recovers to 2.0 × 109/L | through study completion, an average of 21 days. | 
| The neutrophil count nadir from day 3 to day 13 of cycle 1 | The ANC nadir from day 3 to day 13 of cycle 1 | day 3 to day 13 of cycle 1（each cycle is 21 days）. | 
| the time（days）of ANC nadir returns to 2.0 × 109/L | The time (days) of ANC nadir recovers to 2.0 × 109/L | through study completion, an average of 21 days. |