Trial to Compare the Efficacy and Safety Of MW05 and PEG-rhG-CSF

A Phase II/III,Multi-Center,Randomized,Double-blind,Active-Controlled Trial to Compare the Efficacy , Safety and Immunogenicity of MW05 and PEG-rhG-CSF in Prophylactic Treatment for Chemotherapy-Induced Neutropenia

Sponsors

Lead Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

Source Mabwell (Shanghai) Bioscience Co., Ltd.
Brief Summary

In the study, subjects will scheduled to undergo four 21-days cycles of chemotherapy treatment. Three group were treated with MW05 300 μg/kg or MW05 500 μg/kg or PEG-rhG-CSF 100 μg/kg on the 3th day of each cycle randomized 1:1:1 .

The dose of the experimental drug MW05 in phase III were determined by independent data monitoring committee (IDMC) according to the efficacy and safety of phase II. Subjects were randomly divided into two groups 1:1 to received either MW05 or PEG-rhG-CSF(100 μg/kg) on the 3th day of each chemotherapy cycle.

Detailed Description

Study Stage: Phase II/III Study Population Female patients with breast cancer will be enrolled to receive at least 4 cycles of TC chemotherapy, that is: Docetaxel 75 mg/m2 and Cyclophosphamide 600 mg/m2.

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

Overall Status Not yet recruiting
Start Date September 21, 2020
Completion Date September 30, 2023
Primary Completion Date August 30, 2022
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
The primary objective of this study will be to evaluate the efficacy of MW05 pre-filled syringe as compared to PEG-rhG-CSF standard dosing (6 mg) in the first chemotherapy cycle. in cycle 1(each cycle is 21 days)
Secondary Outcome
Measure Time Frame
The duration of grade 4 neutropenia in cycle 2~4 assessed by ANC(ANC < 0.5 × 109/L) in cycles 2-4, in overall 3 cycles(each cycle is 21 days)
The incidence of grade 4 neutropenia in cycle 1~4 assessed by ANC(ANC < 0.5 × 109/L) through study completion, in overall 4 cycles(each cycle is 21 days)
The incidence of grade 3 or 4 neutropenia in cycle 1~4 assessed by ANC(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 duration of grade 3 or 4 neutropenia In cycle 1~4 assessed by ANC(ANC < 1.0 × 109/L and ANC < 0.5 × 109/L, respectively) through study completion, in overall 4 cycles(each cycle is 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) through study completion, in overall 4 cycles(each cycle is 21 days)
The proportion of subjects rescued by short-acting G-CSF in cycle 1~4. through study completion, in overall 4 cycles(each cycle is 21 days)
Enrollment 348
Condition
Intervention

Intervention Type: Drug

Intervention Name: MW05

Description: Recombinant (yeast secreted) human serum albumin-human granulocyte colony stimulating factor (I) fusion protein injection

Other Name: MW05 injection

Intervention Type: Drug

Intervention Name: PEG-rhG-CSF

Description: PEGylated Recombinant Human Granulocyte Colony-Stimulating Factor

Arm Group Label: PEG-rhG-CSF

Other Name: PEG-rhG-CSF injection

Eligibility

Criteria:

Inclusion Criteria:

1. 18~70 years old female(including threshold)

2. Diagnosed with breast cancer .

3. Weight≥45kg.

4. Patients planned to receive TC chemotherapy.

5. ECOG ≤ 1

6. Estimated survival time ≥ 3 months, and could received at least 4 cycles chemotherapy treatment.

7. Have suitable organs and hematopoietic function

8. ECG examination is normal or abnormal has no clinical significance.

9. B-ultrasound examination of abdomen showed no obvious abnormality of spleen.

10. Willing to sign the informed consent form and able to comply with protocol requirements.

11. Non-menopausal or non-surgically sterilized female subjects, the blood pregnancy test results must be negative at the time of screening, and within at least 3 months from the signing of the informed consent form to the end of the last administration, consent to abstinence or the use of effective contraceptive methods.

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Exclusion Criteria:

1. History of other malignant tumors (skin basal cell carcinoma, skin squamous cell carcinoma and / or carcinoma in situ after radical resection can be included in the group after being cured for more than 5 years)

2. Primary hematological diseases, including but not limited to myelodysplastic syndrome, aplastic anemia, sickle cell anemia and other hematological diseases that affect bone marrow hematopoiesis.

3. With known central nervous system metastasis or suspected central nervous system metastasis based on clinical manifestations.

4. With previous history of bone marrow transplantation and / or stem cell transplantation.

5. Currently uncontrolled infections or have received systematic anti-infective therapy within 72 hours before randomization.

6. Serious chronic diseases of important organs such as kidney and liver.

7. Severe heart disease, including but not limited to:history of congestive heart failure (New York College of Cardiology [NYHA] II or higher heart disease)Angina pectoris that needs to be treated with anti-angina pectoris drugsUncontrollable hypertension (systolic blood pressure ≥ 180 mmHg and / or diastolic blood pressure ≥ 100 mmHg)Arrhythmias requiring drug treatment

8. Severe diabetes (such as fundus disease or diabetic foot), or blood sugar is still not well controlled after active treatment.

9. Surgery within 2 weeks before chemotherapy or radiotherapy within 4 weeks (except for patients whose physical condition has recovered and can accept the relevant procedures of this study, as determined by the researchers)

10. Adverse reactions from previous treatments failed to recover to CTCAE v5.0 score ≤ 1 (except for alopecia and other toxic reactions that researchers believe do not affect the safety of this chemotherapy)

11. According to the researchers, there are serious risks to the safety of patients or concomitant diseases that affect the completion of the study.

12. Participated in clinical trials of any other drugs within 4 weeks.

13. Received the same efficacy drugs(such as PEG-rhG-CSF or rhG-CSF, etc.) are still in 5 half-lives or within 28 days (whichever is shorter).

14. With allergic disease or allergic constitution, and who have previously been allergic to any drug or its components in this trial.

15. Active hepatitis B (HBsAg positive and HBV-DNA copy number greater than the normal limit) and / or active hepatitis C (hepatitis C virus antibody positive and HCV-RNA copy number greater than the normal limit) and / or human immunodeficiency virus antibody positive and / or Treponema pallidum antibody.

16. Drug abuse. history or drug abusers

17. Pregnant or lactating women

18. Who have been judged by the researchers to be unsuitable for selection or who are not suitable for other reasons

Gender: Female

Gender Based: Yes

Gender Description: Female patients with breast cancer who require chemotherapy and are planned to receive at least 4 cycles of TC chemotherapy, namely Docetaxel 75 mg/m2 and Cyclophosphamide 600 mg/m2

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Verification Date

July 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Number Of Arms 3
Arm Group

Label: MW05 300μg/kg

Type: Experimental

Description: Subjects will receive MW05(300 μg/kg s.c.) on day 3 of each cycle (6~10 a.m.)

Label: MW05 500μg/kg

Type: Experimental

Description: Subjects will receive MW05(500 μg/kg s.c.) on day 3 of each cycle (6~10 a.m.)

Label: PEG-rhG-CSF

Type: Active Comparator

Description: Subjects will receive PEG-rhG-CSF(100 μg/kg s.c.) on day 3 of each cycle (6~10 a.m.)

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Supportive Care

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov