Efficacy and Safety of MW032 and Xgeva® in Subjects With Bone Metastases From Solid Tumors

NCT04812509 | Completed Phase 3 DMC

• 1 other identifier: MW032-2019-CP301
• Study Type: interventional
• Target: 708
• Locations: 1 country
• Sites: 1

Brief Summary

A multi-center, randomized, double-blind, parallel controlled Phase III clinical study to evaluate the clinical efficacy and safety of MW032 and Xgeva® in patients with bone metastases from solid tumors.

Conditions

Bone Metastases

Keywords

Denosumab; Biosimilarity; pharmacokinetics; pharmacodynamics; safety

Outcome Measures

Primary Outcomes (1)

• uNTx/uCr

  Compare MW032 and Xgeva® for percentage change in bone conversion index (BTM) - urinary type I collagen cross-linked peptide (uNTx) adjusted for urinary creatinine (uCr) in Chinese subjects with solid tumor bone metastasis (uNTx/uCr from baseline to week 13)

  from baseline to week 13

Secondary Outcomes (3)

• uNTx/uCr

  from baseline to weeks 5,25,37 and 53

• S-BALP

  from baseline to weeks 5,13,25,37 and 53

• SRE

  from baseline to week 53

Study Arms (2)

MW032

EXPERIMENTAL

MW032 injection(120mg) was administered subcutaneously once every 4 weeks for a maximum of 13 consecutive doses throughout the trial, according to the investigator's assessment.

Drug: MW032

Xgeva®

ACTIVE COMPARATOR

Xgeva® injection(120mg) was administered subcutaneously every 4 weeks for a maximum of 13 cumulative doses throughout the trial,according to the investigator's assessment.

Drug: Xgeva

Interventions

MW032 DRUG

The active ingredient of MW032 is a recombinant human anti-RANKL monoclonal antibody ,subcutaneous injection of 120 mg (1.7ml)every 4 weeks for a maximum of 13 consecutive doses throughout the trial.

Also known as: recombinant human anti-RANKL monoclonal antibody injection

MW032

Xgeva DRUG

The active ingredient of Xgeva® is denosumab,subcutaneous injection of 120 mg (1.7ml)every 4 weeks for a maximum of 13 consecutive doses throughout the trial.

Also known as: Denosumab Injection

Xgeva®

Eligibility Criteria

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

You may qualify if:

• Pathological confirmed malignant tumors (except hematological tumors);
• Bone metastasis diagnosed by imaging (bone X-ray, CT scanning or magnetic resonance scanning) or pathology (bone biopsy) can be examined within 3 months before signing the informed consent,according to 《The expert consensus on clinical diagnosis and treatment of bone metastases and bone related diseases of malignant tumors (2014)》；
• No limited of gender,age ≥ 18 years old;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
• Estimated survival time was more than 6 months;
• Subjects must have adequate organ function at baseline as defined below:① hematology: neutrophils ≥ 1,500/mcL, platelets ≥ 75,000/mcL, hemoglobin ≥ 80 g / L; ② renal function: creatinine (CR) clearance rate ≥ 30 ml / min; ③ Liver function: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were less than or equal to 2.0 × upper normal limit (ULN) in subjects without liver metastasis; ALT and AST were less than or equal to 5.0 × ULN in subjects with liver metastasis; serum total bilirubin was less than or equal to 1.5 × ULN; ④ serum calcium (albumin correction) was more than or equal to 2.0 mmol / L (8.0 mg / dl) but less than or equal to 2.9 mmol / L (11.5 mg / dl). Note: calcium supplements should not be used at least 8 hours before serum calcium determination in screening period;
• Subjects has understood the nature and purpose of the study, as well as the research procedure, and the subject has signed the written informed consent;

You may not qualify if:

• Subjects with diseases not suitable for the study,in the Investigator's opinion (according to the subject's report or medical record review), such as:Other malignant tumors (different from the malignant solid tumors required in this study protocol) occurred within 3 years before enrollment, and in the active period;Other diseases affecting bone metabolism, such as vitamin D deficiency rickets, osteomalacia and primary osteoporosis, hyperparathyroidism, osteitis deformans, etc. (excluding osteoporosis);Human immunodeficiency virus or Treponema pallidum infection;Unstable liver disease, active period of hepatitis B virus or hepatitis C virus infection;Other serious or unstable physical or mental disorders.
• Brain metastasis.
• Oral and dental diseases: previous or current evidence of osteomyelitis or necrosis of the jaw; acute dental or mandibular diseases, need to be treated oral surgery; planned invasive dental surgery; failed dental or oral surgery.
• Subjects with bone metastases need radiotherapy or surgery.
• Previous treatment with denosumab.
• Patients who had received any kind of intravenous or oral bisphosphonates before administration of the first study drug.

Sponsors & Collaborators

• Mabwell (Shanghai) Bioscience Co., Ltd.: lead

Study Sites (1)

Fifth Medical Center of PLA General Hospital

Beijing, Beijing Municipality, 100011, China

Location

Related Publications (1)

• Zhang S, Yin Y, Xiong H, Wang J, Liu H, Lu J, Zhang Q, Zhang L, Zhong J, Nie J, Lei K, Wang H, Yang S, Yao H, Wu H, Yu D, Ji X, Zhang H, Wu F, Xie W, Li W, Yao W, Zhong D, Sun H, Sun T, Guo Z, Wang R, Guo Y, Yu Z, Li D, Jin H, Song H, Chen X, Ma W, Hu Z, Liu D, Guo Y, Tang J, Jiang Z. Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial. JAMA Oncol. 2024 Apr 1;10(4):448-455. doi: 10.1001/jamaoncol.2023.6520.

  PMID: 38329745 DERIVED

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 23, 2021
• Study Start: March 20, 2020
• Primary Completion: April 29, 2021
• Study Completion: January 28, 2022
• Last Updated: February 24, 2023

Record last verified: 2023-02

Locations

CN (1)