CTRI/2022/05/042823招募中3 期
A Randomized, Multiple-dose, Multicenter, Comparative Parallel Study to Evaluate thePharmacokinetic, Pharmacodynamic, Efficacy and Safety of Subcutaneous Injection ofDenosumab (Hetero) and Reference Medicinal Product (Denosumab, Amgen Inc.) in patientswith bone metastases from solid tumors.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 282
- 试验地点
- 32
- 主要终点
- Proportion patients with first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.
研究概览
简要总结
This study is a double blind, randomized, active controlled, parallel group clinical study to evaluate the efficacy, safety, and pharmacokinetics of subcutaneous route of administration for the Hetero-Denosumab and Amgen-Denosumab in patients with bone metastases from solid tumorsPatients will be screened for study eligibility based on the inclusion and exclusion criteria. Patients eligible for the study will be randomized to either Hetero-Denosumab or Reference Medicinal Product (Amgen-Denosumab) based on the randomization schedule. All patients shall be administered sub cutaneous injection of 120 mg Denosumab every 4 weeks for 24 weeks. All patients will be followed up for 28 weeks for efficacy and safety assessments. The study is expected to be completed in approximately 18 months after dosing of the first patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, variable
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients of ≥
- •65 years of age.
- •Patients with current/ prior radiographic (X-ray, CT or MRI) evidence of at least one bone metastases from solid tumors.
- •Patients with ECOG score
- •Patients with ability to understand the study procedures and the risks involved, willing to provide written Informed Consent, and able to adhere to study schedules and requirements.
- •Patients with screening laboratory tests within the following criteria: a. Hemoglobin ≥9.0 g/dL b. White blood cells ≥3.5 X 109/L c. Absolute neutrophil count ≥1.5 X 109/L d. Platelets ≥100 X 109/L e. Serum transaminase levels ≤2.5 X ULN (≤5 X ULN, in case of liver metastases) f. Alkaline phosphatase levels ≤5 X ULN g. Serum creatinine levels ≤150 μmol/L (≤1.7mg/dL) h. Serum calcium (corrected) levels ≥8 to ≤11.5 mg/dL (2 to 2.9 mmol/L)
- •Women of childbearing potential should neither become pregnant nor lactate and must be using barrier methods of birth control measures during the study period and for 6 months after receiving the last injection of study medication.
排除标准
- •Patients with history of hypersensitivity to the denosumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins.
- •Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab).
- •Prior intravenous bisphosphonate treatment or current/prior oral bisphosphonates for treatment of bone metastases.
- •Patients who had disorders associated with abnormal bone metabolism including uncontrolled hyperthyroidism or hypothyroidism (except subjects on stable thyroid hormone replacement therapy for last one year), hyperparathyroidism or hypoparathyroidism, Paget’s disease, osteomalacia, osteogenesis imperfecta, cushing’s disease or hyperprolactinemia.
- •Patients with untreated or symptomatic brain metastases.
- •Patients receiving systemic corticosteroids; or received calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks of randomization.
- •Patients requiring radiotherapy or surgery to bone metastases.
- •Patient with severe renal impairment (creatine clearance <30 mL/min) or receiving dialysis.
- •Patients with current or previous osteonecrosis or osteomyelitis of the jaw or non-healed dental/oral surgery or any planned invasive dental procedure during the study.
- •Severe and/or uncontrolled conditions which could compromise participation in the study: Uncontrolled blood pressure (>140/90 mm of Hg); Unstable angina; Congestive heart failure (NYHA grade 3 or more, History of myocardial infarction or stroke within previous 6 months of randomization; Symptomatic arrhythmia requiring medication.
- •Current signs or symptoms of significant, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease that renders the subject incapable of participating in the study.
- •Patients with current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
- •History or presence of any medical or psychiatric condition or disease, or clinically significant laboratory abnormality, physical examination findings or any other condition that, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation and may prevent the subject from completing the study.
- •History of cirrhosis of the liver or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
- •Patients with a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment.
- •Participation in any clinical study of an investigational product within the previous 3 months.
结局指标
主要结局
Proportion patients with first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.
时间窗: 24 weeks
次要结局
- Time to first and subsequent on-study SREs associated with bone metastases/lesions.(Week 12 and Week 24)
- Proportion of patients with first and subsequent on-study SREs associated with bone metastases/lesions.(Week 12 and Week 24)
- Pharmacodynamic assessment - Percentage change in uNTx/Cr in patients with bone metastases from solid tumors.(From Baseline to Week 4, 8, 12 and 24.)
- Comparative safety and tolerability for treatment emergent adverse events.(Throughout the study period)
- Pharmacokinetic parameters comparison of Cmax, AUC0-t, AUC0-28day.(After First Dose Administration)
- Median time to first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.(24 weeks)
- Mean number of on-study SREs associated with bone metastases/lesions.(Week 12 and Week 24)
- Comparative incidence and titers of anti-Denosumab antibodies.(Week 12 and Week 24)
研究者
研究点 (32)
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