A Multicenter, Randomized, Controlled, Non-inferiority Study of Narlumosbart Compared With Denosumab in the Treatment of Bone Disease in Patients With Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 478
- 主要终点
- Percent change from baseline in urinary N-terminal telopeptide of type 1 collagen corrected for urinary creatinine (uNTx/uCr) at week 13
研究概览
简要总结
The purpose of this study is to determine if narlumosbart is non-inferior to denosumab in the treatment of bone diseases from multiple myeloma (MM).
详细描述
Multiple myeloma is a plasma cell dyscrasia with a high likelihood of causing bone disease (ie, multiple myeloma-related bone disease); as a result, up to 80% of patients with newly diagnosed multiple myeloma present with osteolytic lesions.
Denosumab is recommended for the treatment of newly diagnosed multiple myeloma, and for patients with relapsed or refractory multiple myeloma with evidence of multiple myeloma-related bone disease.
Narlumosbart is a recombinant, fully human, anti-receptor activator of nuclear factor kappa-Β ligand (RANKL) IgG4 monoclonal antibody. Changing the IgG2 Fc portion of denosumab to IgG4, results in increased stability, higher specificity and affinity for RANKL than denosumab. The objective of this phase III trial is to compare the efficacy and safety between Narlumosbart and denosumab in patients with bone diseases from newly diagnosed multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects fully understand and voluntarily participate in this study and sign the informed consent;
- •Age≥18, no gender limitation;
- •Active multiple myeloma patients with newly diagnosed by International Myeloma Working Group (IMWG) 2014 criteria;
- •Measurable lesion per at least one of the following criteria : Serum monoclonal protein ≥10 g/L; Urinary monoclonal protein ≥200 mg/24h; Serum free Light Chain (FLC) assay showed an involved FLC level ≥100 mg/L with abnormal ratio for FLC (κ/λ);
- •Radiographic [X-ray, computer tomography (CT), magnetic resonance imaging (MRI), positons emission tomography coupled with a computer tomography (PET-CT)] evidence of at least one lytic bone lesion;
- •Plan to receive primary frontline anti-myeloma therapies, or receiving less than one cycle of frontline anti-myeloma therapy (less than 30 days, does not include radiotherapy or a single short course of steroid), the treatment regimens were limited to VRd, D-VRd, DRd, and VCd;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Adequate organ function, as defined by the following criteria (per laboratory values):
- •Liver function: Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN), Serum alanine aminotransferase ≤ (ALT) 2.0 x ULN, Serum aspartate aminotransferase (AST) ≤ 2.0 x ULN
- •Renal function: Serum creatinine clearance (CrCL) ≥ 30 mL/min, calculated by the Cockcroft-Gault formula
- •Serum calcium or albumin-adjusted serum calcium ≥2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)
- •Reproductive potential subjects should be receiving effective contraception (Both male and female reproductive potential subjects, from the date of signing the informed consent to 6 months after the end of treatment);
- •Expected survival time ≥ 3 months;
排除标准
- •POEMS syndrome;
- •Plasma cell leukemia;
- •Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; Non-healed dental/oral surgery, including tooth extraction; Active dental or jaw condition which requires oral surgery; Planned invasive dental procedures;
- •Planned radiation therapy or Orthopedic surgery;
- •Prior administration of denosumab or bisphosphonates;
- •Patients with active bone metabolic diseases (Paget disease of bone, Cushing syndrome and hyperprolactinemia), rheumatoid arthritis, uncontrolled hyper/hypothyroidism or hyper/hypoparathyroidism;
- •Uncontrolled concurrent diseases, including but not limited to: symptomatic congestive heart failure, hypertension (blood pressure remains > 150/90 mmHg after standard therapy), unstable angina, arrhythmia requiring medication or instruments, history of myocardial infarction within 6 months, echocardiography showing left ventricular ejection fraction <50%;
- •Active bacterial or fungal infections requiring systemic treatment within 7 days before randomization;
- •Known infection with human immunodeficiency virus (HIV), active infection with Hepatitis B virus (positive hepatitis B surface antigen and positive HBV-DNA) or Hepatitis C virus(positive hepatitis C surface antigen and positive HCV-RNA);
- •Pregnancy (serum β-HCG positive) or lactation;
- •Use of any of the following anti-bone metabolism drugs within 6 months before enrollment:
- •parathyroid hormonerelated peptides
- •osteoprotegerin
- •mithramycin
- •strontium ranelate
- •Known sensitivity to narlumosbart, denosumab, calcium or vitamin D;
- •Any other factors not suitable for participation in this study that in the opinion of the investigator.
研究组 & 干预措施
Narlumosbart
120 mg SC Q4W, up to 2 years.
干预措施: Narlumosbart (Drug)
Denosumab
120 mg SC Q4W, up to 2 years.
干预措施: Denosumab (Drug)
结局指标
主要结局
Percent change from baseline in urinary N-terminal telopeptide of type 1 collagen corrected for urinary creatinine (uNTx/uCr) at week 13
时间窗: From baseline to week 13
Compare narlumosbart and denosumab for percentage change in bone turnover marker (BTM) - urinary N-terminal telopeptide of type 1 collagen (uNTx) corrected for urinary creatinine (uCr) (uNTx/uCr from baseline to week 13)
次要结局
- The proportion of subjects with a change in uNTx/uCr greater than 65% from baseline to week 13(From baseline to week 13)
- Overall Survival(From baseline to 90 days after the last dose, up to approximately 30 months)
- Percent changes of serum bone alkaline phosphatase (BALP) and serum C-terminal telopeptide of type 1 collagen (sCTX-I)(From baseline to week 13)
- Time to first on-study skeletal related event(From baseline to 90 days after the last dose, up to approximately 30 months)
- Incidence and type of adverse events (AEs)(From the first dose finished to 28 days after the last dose)
- Percentage of participants with an on-study SRE at different time points(Months 3, 6, 12, 18 and 24)
- Time to first and subsequent on-study SRE(From baseline to 90 days after the last dose, up to approximately 30 months)