An open-label, multi-center, randomized, active controlled, comparative, phase III clinical study to assess efficacy and safety of Lupin’s Filgrastim versus Neupogen® as an adjunct to chemotherapy for prevention of neutropenia in patients with non-myeloid malignancies
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 98
- 试验地点
- 9
- 主要终点
- •Duration of severe neutropenia [ANC 0.5 x 109/L] in cycle 1 of chemotherapy
研究概览
简要总结
Filgrastim is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. Filgrastim was initially used as an adjunct to chemotherapy for reducing risk of neutropenia, one of the major adverse events of cancer chemotherapy. Its use has led to reduced infections and hospital admissions for patients with cancer.Lupin Limited, India has developed a biosimilar Filgrastim for the prevention of chemotherapy induced neutropenia in patients undergoing chemotherapy. As with other biosimilar products previously developed by other manufacturers, Lupin Limited intends to evaluate the efficacy and safety of its formulation and compare the same with existing Filgrastim formulation, Neupogen® (marketed by Roche India) to assess clinical equivalence.
This is an open-label, multi-center, randomized, active-controlled, two-arm parallel study to assess the efficacy, safety and tolerability of biosimilar Filgrastim (manufactured by Lupin Limited, India) given subcutaneously as compared to Neupogen® (Filgrastim marketed by Roche India). xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
· The total duration of the study(Per patient) will be approximately 42 ± 3 days.
· The study consists of pre-study or screening period of maximum 2 days.
- Eligible patients will be randomized to receive either Lupin’s Filgrastim or Neupogen® starting after 24 hours of chemotherapy for 2 chemotherapy cycles (of maximum 21 days each).
- Efficacy and safety assessments will be conducted on different days
Study Hypothesis:
Primary outcome of the study is Duration of severe neutrpenia(DSN) in cycle 1
Equivalence of biosimilar Filgrastim and Neupogen® will be assessed based on the per proptocol(PP) set, using the ANCOVA model to calculate a two-sided 95% confidence interval for “Test product (Lupin’s Filgrastim) minus Neupogen®”. Equivalence to be concluded if this confidence interval lay entirely within the equivalence rage [−1 day, +1 day]
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients must be able and willing to give written informed consent prior to any study-related procedures.
- •2.Male or non-pregnant / non-lactating female patients between 18-65 years of age 3.Patients with histologically or cytologically confirmed non-myeloid malignancy 4.Patients planned to have myelosuppressive chemotherapy regimen that consist at least one chemotherapeutic agent from docetaxel, doxorubicin or paclitaxel.
- •5.Patients who have not received myelosuppressive chemotherapy within last 12 months of screening.
- •6.Patients with baseline ANC of ¡Ý 1 x 109/L and platelet count ¡Ý 100 x 109/L.
- •7.Patients with adequate hepatic and renal function [defined as Alkaline Phosphatase ¡Ü 5 X Upper limits of normal (ULN), serum SGOT and SGPT ¡Ü 2.5 X ULN (¡Ü 5 X ULN for patient with liver involvement) , Total bilirubin ¡Ü 1.5 X ULN and Creatinine ¡Ü 1.5 X ULN of the reference range at the screening assessment] 8.Patients with ECOG Performance status of 0 or 1.
排除标准
- •1.Patients with history of hypersensitivity to study drugs, components or similar products.
- •2.Patients with myeloid malignancies and myelodysplasia 3.Patients currently receiving radiation therapy or have completed radiation therapy within 4 weeks before study entry 4.Patients with prior bone marrow or stem cell transplantation.
- •5.Patients with chronic use of oral corticosteroids.
- •(Except ¡Ü 20 mg/day dose of prednisolone).
- •6.Patients with underlying neuropathy of Grade 2 or higher.
- •7.Patients with history of systemic antibiotic use within 72 hours prior to chemotherapy.
- •[However if patient is receiving antibiotics during screening, then chemotherapy can be started after 72 hours of last antibiotic dose.
- •8.Patients with any active infection which may require systemic antimicrobial therapy during the study.
- •9.Patients who have received hematopoietic growth factors (e.g. G-CSF, peg-G-CSF, erythropoietin) or cytokines (e.g. interleukins, interferons) within last 1 month of screening.
- •10.Known cases of HIV or HBV or HCV seropositive patients.
- •11.Known cases of Sickle Cell Anemia.
- •12.Patients with radiographic evidence of active pulmonary infections and/or recent history of pneumonia within 1 month of screening.
- •13.Patients with clinically evident splenomegaly confirmed subsequently by ultrasonography.
- •14.Patients with any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the patient¡¯s involvement in the study or overall interpretation of the data.
- •15.Alcoholic or drug abuse patients.
- •16.Patients who have participated in another therapeutic clinical study within the past 30 days prior to screening, or are likely to simultaneously participate in another therapeutic clinical study.
- •17.Patients who are doubtful to comply with study procedures for mental, psychological or social reasons.
- •18.Women of child-bearing potential & all men who are not willing to follow a reliable & effective contraceptive measure during the course of the study & at least 1 month after the last visit.
- •19.Patients with Congestive Heart Failure Class III/IV as per NYHA Classification.
结局指标
主要结局
•Duration of severe neutropenia [ANC 0.5 x 109/L] in cycle 1 of chemotherapy
时间窗: Day 1, 2, 4 to 10, 15, 21(Cycle 1)
次要结局
- Safety:(•Adverse event (AE) assessment (as per NCI CTCAE Ver.4.0))
- assement of the neutropenia observed in the study with respect to DSN in cyecle 2, percentage of patients with neutrpoenia in the study, depth of ANC Nadir, time to ANC recovery(Day 1, 2, 4 to 10, 15, 21(Cycle 2))
- Incidence of Febrile Neutropenia (FN)by cycle and across the cycles, duration of FN, Rate of the hospitalization due to FN, percentage of the patients requiring system antibiotic to treat FN by cycle and acrros the cycle(In both the cycles, day 1 to day 21)