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

A Multi-center, Randomized, Double-blind, Parallel Controlled Phase Ⅲ Clinical Study to Evaluate the Efficacy and Safety of Recombinant Human Anti RANKL Monoclonal Antibody Injection (MW032) and Denosumab (Xgeva®) in Subjects With Bone Metastases From Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Bone Metastases
• Intervention / Treatment: Drug: MW032; Drug: Xgeva

Detailed Description

This is A multi-center, randomized, double-blind, parallel controlled Phase III clinical trial.

The primary objective is to evaluate the clinical efficacy of MW032 and Xgeva® in patients with bone metastases from solid tumors.

The secondary objective are to evaluate the clinical safety and immunogenicity of MW032 and Xgeva® in patients with bone metastases from solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 708
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100011
      • Fifth Medical Center of PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pathological confirmed malignant tumors (except hematological tumors);
2. 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)》；
3. No limited of gender,age ≥ 18 years old;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
5. Estimated survival time was more than 6 months;
6. 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;
7. 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;

Exclusion Criteria:

1. 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.
2. Brain metastasis.
3. 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.
4. Subjects with bone metastases need radiotherapy or surgery.
5. Previous treatment with denosumab.
6. Patients who had received any kind of intravenous or oral bisphosphonates before administration of the first study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MW032; 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; 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.; Other Names: recombinant human anti-RANKL monoclonal antibody injection
Active Comparator: Xgeva®; 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; 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.; Other Names: Denosumab Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
uNTx/uCr	Compare the percentage change in MW032 and Xgeva® for bone conversion indicator uNTx/uCr among subjects with solid tumor metastasis (from baseline to weeks 5,25,37 and 53).	from baseline to weeks 5,25,37 and 53
S-BALP	Compare the changes of bone specific alkaline phosphatase (S-BALP) from baseline to weeks 5,13, 25,37 and 53.	from baseline to weeks 5,13,25,37 and 53
SRE	SRE occurrence	from baseline to week 53

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2020
• Primary Completion (Actual): April 29, 2021
• Study Completion (Actual): January 28, 2022

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 21, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; pharmacodynamics; Biosimilarity; Denosumab
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: MW032-2019-CP301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes