Study to Compare the Efficacy and Safety of F-627 and GRAN® (F-627)

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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Neutropenia
• Intervention / Treatment: Drug: F-627; Drug: GRAN®

Detailed Description

Study Stage: Phase III

Study Population: Female patients with breast cancer will be enrolled to receive at least 4 cycles of Epirubicin + Cyclophosphamide (EC) chemotherapy, that is: epirubicin 100 mg/m^2 and cyclophosphamide 600 mg/m^2.

Study Design: A multi-center, randomized, open-label, active-controlled phase III clinical trial

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing to sign the informed consent form and able to comply with protocol requirements;
2. 18-75 years old;
3. 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/m^2 + cyclophosphamide 600 mg/m^2;
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
5. Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L, hemoglobin (Hb) ≥ 11.0 g/dL, and platelet (PLT) ≥ 100 × 10^9/L prior to enrollment;
6. Hepatic and renal functions: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, serum creatinine ≤ 1.5 × ULN;
7. Left ventricular ejection fraction > 50%;
8. 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:

1. Radiation therapy within 4 weeks prior to enrollment;
2. Patients with breast cancer who have received neoadjuvant chemotherapy before surgery;
3. Prior bone marrow or stem cell transplant;
4. With other malignant tumors other than breast cancer;
5. Patients who have received a treatment with recombinant human granulocyte colony stimulating factor within 6 weeks prior to randomization;
6. Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, ECG or other approaches;
7. With any disease that may cause splenomegaly;
8. With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C;
9. Women in pregnancy or breastfeeding;
10. Known HIV positive or AIDS;
11. 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;
12. With sickle cell anemia;
13. With alcohol or drug abuse that may affect the compliance with the study;
14. With known hypersensitivity to granulocyte colony stimulating factor or excipients;
15. Have received any other investigational drug within 1 month or 5 half-lives of the investigational drugs prior to enrollment (whichever is longer);
16. 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.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: F-627; F-627 (20 mg/dose, s.c.) on day 3 of each cycle, i.e., 48 ± 4 h after the start of chemotherapy	Drug: F-627; Day 3 of each cycle, i.e., 48 ± 4 h after starting chemotherapy; Other Names: Recombinant Human Granulocyte Colony Stimulating Factor-Fc Fusion Protein
Active Comparator: GRAN®; GRAN® [5 μg/kg/day, s.c., once daily (± 4 h) up to 2 weeks or until neutrophil count returns to 5.0 × 10^9/L] on day 3 of each cycle, i.e., 48 ± 4 h after the start of chemotherapy	Drug: GRAN®; Since day 3 of each cycle, i.e., 48 ± 4 h after starting chemotherapy, continuous treatment for ≤ 2 weeks or until ANC recovers to 5.0 × 10^9/L from nadir (investigators may refer to ANC test results from the Department of Laboratory Medicine of each study sites to decide when to discontinue GRAN®); Other Names: Filgrastim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Grade 3 or 4 Neutropenia (ANC <1.0×10^9/L) in Cycle 1	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Grade 3 or 4 Neutropenia in Cycle 1	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 3 or 4 Neutropenia in Cycle 2	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 3 or 4 Neutropenia in Cycle 3	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 3 or 4 Neutropenia in Cycle 4	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 3 or 4 Neutropenia in Cycle 2	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 3 or 4 Neutropenia in Cycle 3	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 3 or 4 Neutropenia in Cycle 4	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 4 Neutropenia in Cycle 1	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 4 Neutropenia in Cycle 2	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 4 Neutropenia in Cycle 3	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 4 Neutropenia in Cycle 4	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L.	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 4 Neutropenia in Cycle 1	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 4 Neutropenia in Cycle 2	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 4 Neutropenia in Cycle 3	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration of Grade 4 Neutropenia in Cycle 4	Grade 4 neutropenia is defined as ANC < 0.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
Overall Duration of Grade 3 or 4 Neutropenia in 4 Cycles	Grade 3 defined as ANC <1.0×10^9/L and Grade 4 defined as ANC<0.5×10^9/L According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Overall 4, 21-day chemotherapy cycles(average 12 weeks)
Number of Participants With Grade 2 or Greater Neutropenia in Cycle 1	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 2 or Greater Neutropenia in Cycle 2	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 2 or Greater Neutropenia in Cycle 3	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Number of Participants With Grade 2 or Greater Neutropenia in Cycle 4	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 1	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 2	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 3	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Duration (Days) of Grade 2 or Greater Neutropenia in Cycle 4	Grade 2 or greater neutropenia is defined as ANC < 1.5 × 10^9/L. According to the study protocol, the outcome measure "Duration of Grade 3 or 4 Neutropenia (days)" applied to all participants with a valid ANC level, rather than those with an ANC level of < 1.0 × 109/L. The value of 0 represents the participant experienced 0 days with Grade 3 or 4 Neutropenia (days). Whereas exclusion of a participant from the analysis indicates a lack of ANC data of the participant. The mean value was calculated as the sum of the durations (days) of ANC < 1.0 × 109/L for all participants with valid ANC level (the numerator) divided by the number of participants (the denominator).	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)
The Absolute Neutrophil Counts (ANC) Nadir From Day 3 to Day 13 of Cycle 1	The minimum value of ANC measured from day 3 to day 13 of cycle 1	From day 3 to day 13 of cycle 1 (11 days)
Number of Participants With Febrile Neutropenia (FN) in Cycle 1	FN is defined as ANC < 1.0 × 10^9/L with fever (a single measurement of body temperature >38.3 °C or body temperature ≥ 38.0 °C for more than 1 hr).	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 1	If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.	Cycle 1, the first of 4, 21-day chemotherapy cycles (average 3 weeks)
Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 2	If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.	Cycle 2, the second of 4, 21-day chemotherapy cycles (average 3 weeks)
Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 3	If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.	Cycle 3, the third of 4, 21-day chemotherapy cycles (average 3 weeks)
Time (Days) of ANC Nadir Recovers to 2.0 × 10^9/L in Cycle 4	If the ANC nadir during the first 13 days of the cycle is < 2.0 × 10^9/L, the recovery time = ((date of ANC ≥ 2.0 ×10^9/L) - (date of ANC reaching nadir within the cycle) + 1). If the ANC nadir in the first 13 days of the cycle is ≥2.0 × 10^9/L, then the recovery time = 0 days.	Cycle 4, the last of 4, 21-day chemotherapy cycles (average 3 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the potential immunogenicity of F-627 by testing anti-F-627 antibodies inserum	To evaluate the immunogenic potential of F-627 by testing serum anti-F-627 antibodies.	8 months

Collaborators and Investigators

• Sponsor: EVIVE Biotechnology
• Investigators: Principal Investigator: Zhimin Shao, Doctor, Fudan University Shanghai Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Actual): January 24, 2019
• Study Completion (Actual): June 19, 2019

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Leukocyte Disorders; Hematologic Diseases; Leukopenia; Agranulocytosis; Neutropenia; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: SP11631

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No