Narlumosbart Compared With Denosumab in Patients With Multiple Myeloma Bone Disease

Phase 3

Not yet recruiting

• Conditions: Multiple Myeloma; Bone Diseases
• Interventions: Drug: Narlumosbart; Drug: Denosumab

• Registration Number: NCT06314698
• Lead Sponsor: RenJi Hospital

Brief Summary

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).

Detailed Description

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.
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Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-10
• Study First Submitted QC: 2024-03-14
• Last Update Submitted: 2024-03-14
• Study First Posted: 2024-03-18
• Last Update Posted: 2024-03-18
• Study Start: 2024-04-01
• Primary Completion: 2024-12-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 478

Inclusion Criteria

1. Subjects fully understand and voluntarily participate in this study and sign the informed consent;

2. Age≥18, no gender limitation;

3. Active multiple myeloma patients with newly diagnosed by International Myeloma Working Group (IMWG) 2014 criteria;

4. 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);

5. 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;

6. 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;

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

8. Adequate organ function, as defined by the following criteria (per laboratory values):

   1. 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
   2. Renal function: Serum creatinine clearance (CrCL) ≥ 30 mL/min, calculated by the Cockcroft-Gault formula
   3. Serum calcium or albumin-adjusted serum calcium ≥2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)

9. 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);

10. Expected survival time ≥ 3 months;

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Exclusion Criteria

1. POEMS syndrome;

2. Plasma cell leukemia;

3. 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;

4. Planned radiation therapy or Orthopedic surgery;

5. Prior administration of denosumab or bisphosphonates;

6. Patients with active bone metabolic diseases (Paget disease of bone, Cushing syndrome and hyperprolactinemia), rheumatoid arthritis, uncontrolled hyper/hypothyroidism or hyper/hypoparathyroidism;

7. 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%;

8. Active bacterial or fungal infections requiring systemic treatment within 7 days before randomization;

9. 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);

10. Pregnancy (serum β-HCG positive) or lactation;

11. Use of any of the following anti-bone metabolism drugs within 6 months before enrollment:

    1. parathyroid hormonerelated peptides
    2. calcitonin
    3. osteoprotegerin
    4. mithramycin
    5. strontium ranelate

12. Known sensitivity to narlumosbart, denosumab, calcium or vitamin D;

13. Any other factors not suitable for participation in this study that in the opinion of the investigator.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Narlumosbart	Narlumosbart	120 mg SC Q4W, up to 2 years.
Denosumab	Denosumab	120 mg SC Q4W, up to 2 years.

Primary Outcome Measures

Name	Time	Method
Percent change from baseline in urinary N-terminal telopeptide of type 1 collagen corrected for urinary creatinine (uNTx/uCr) at week 13	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)

Secondary Outcome Measures

Name	Time	Method
The proportion of subjects with a change in uNTx/uCr greater than 65% from baseline to week 13	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%)
Overall Survival	From baseline to 90 days after the last dose, up to approximately 30 months	Overall survival was defined as the time interval (in days) from the randomization date to the date of death.
Percent changes of serum bone alkaline phosphatase (BALP) and serum C-terminal telopeptide of type 1 collagen (sCTX-I)	From baseline to week 13	Compare the changes of BALP and sCTX-I from baseline to weeks 13
Time to first on-study skeletal related event	From baseline to 90 days after the last dose, up to approximately 30 months	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
Incidence and type of adverse events (AEs)	From the first dose finished to 28 days after the last dose	To identify the incidence and the type of AEs, including abnormalities in clinical, laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams.
Percentage of participants with an on-study SRE at different time points	Months 3, 6, 12, 18 and 24	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 to first and subsequent on-study SRE	From baseline to 90 days after the last dose, up to approximately 30 months	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.; ...