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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
478
Administered by subcutaneous injection once every 4 weeks.
Administered by subcutaneous injection once every 4 weeks.
Percent change from baseline in urinary N-terminal telopeptide of type 1 collagen corrected for urinary creatinine (uNTx/uCr) at 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)
Time frame: From baseline to week 13
The proportion of subjects with a change in uNTx/uCr greater than 65% from baseline to week 13
Compare narlumosbart and denosumab for the proportion of subjects with a change in uNTx/uCr greater than 65% from baseline to week 13 (uNTx/uCr from baseline to week 13 \>65%)
Time frame: From baseline to week 13
Time to first on-study skeletal related event
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE
Time frame: From baseline to 90 days after the last dose, up to approximately 30 months
Percentage of participants with an on-study SRE at different time points
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression. Percentage of participants with an on-study SRE at 3, 6, 12, 18 and 24 months
Time frame: Months 3, 6, 12, 18 and 24
Time to first and subsequent on-study SRE
Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE.
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Time frame: 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)
Compare the changes of BALP and sCTX-I from baseline to weeks 13
Time frame: From baseline to week 13
Overall Survival
Overall survival was defined as the time interval (in days) from the randomization date to the date of death.
Time frame: From baseline to 90 days after the last dose, up to approximately 30 months
Incidence and type of adverse events (AEs)
To identify the incidence and the type of AEs, including abnormalities in clinical, laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams.
Time frame: From the first dose finished to 28 days after the last dose