Narlumosbart Compared With Denosumab in Patients With Multiple Myeloma Bone Disease

NCT06314698 | Not Yet Recruiting Phase 3

• 1 other identifier: IIT-2024-0011
• Study Type: interventional
• Target: 478
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Multiple Myeloma; Bone Diseases

Outcome Measures

Primary Outcomes (1)

• 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)

  From baseline to week 13

Secondary Outcomes (7)

• The proportion of subjects with a change in uNTx/uCr greater than 65% from baseline to week 13

  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

• 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

• Percent changes of serum bone alkaline phosphatase (BALP) and serum C-terminal telopeptide of type 1 collagen (sCTX-I)

  From baseline to week 13

Study Arms (2)

Narlumosbart

EXPERIMENTAL

120 mg SC Q4W, up to 2 years.

Drug: Narlumosbart

Denosumab

ACTIVE COMPARATOR

120 mg SC Q4W, up to 2 years.

Drug: Denosumab

Interventions

Narlumosbart DRUG

Administered by subcutaneous injection once every 4 weeks.

Also known as: Narlumosbart Injection, JMT103

Narlumosbart

Denosumab DRUG

Administered by subcutaneous injection once every 4 weeks.

Also known as: XGEVA®, AMG 162

Denosumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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
• calcitonin
• osteoprotegerin
• mithramycin

Sponsors & Collaborators

• RenJi Hospital: lead
• Shanghai JMT-Bio Inc.: collaborator

Related Publications (1)

• Dhillon S. Narlumosbart: First Approval. Drugs. 2024 Jan;84(1):105-109. doi: 10.1007/s40265-023-01985-3.

  PMID: 38112898 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Bone Diseases

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jian Hou, M.D.

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Honghui Huang, M.D.

CONTACT

00862168383141; honghui_huang@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: March 18, 2024
• Study Start: April 1, 2024
• Primary Completion: December 31, 2024
• Study Completion (Estimated): April 30, 2027
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share