Safety, Tolerability and PK/PD of JMT103 in Patients With Bone Metastases From Tumors (JMT103)

A Phase I, Multi-center, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability and Preliminary Pharmacokinetics/Pharmacodynamics of JMT103 in Patients With Bone Metastases From Tumors

JMT103 is a novel, full human IgG4 monoclonal antibody targeting RANKL. In preclinical studies, JMT103 demonstrated strong activity through blocking RANKL receptor, RANK on the surface of osteoclasts, leading to inhibit osteoclast differentiation, activation, and maturation and reduce bone resorption.

This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) ,to evaluate the safety, pharmacokinetics and preliminary efficacy (bone turnover markers) of recombinant fully human Anti-RANKL Monoclonal Antibody (JMT103) in patients with bone metastases from tumors at single doses and multiple doses.

About 36 cases patients are to be recruited.

Study Overview

• Status: Unknown
• Conditions: Bone Metastases
• Intervention / Treatment: Biological: Anti-RANKL Monoclonal Antibody

Detailed Description

This is a Phase I, first-in-human, multi-center, open-label dose escalation clinical study of recombinant fully human Anti-RANKL Monoclonal Antibody (JMT103) administered subcutaneously to patients with bone metastases from tumors.

The study includes two phases: dose escalation study and expansion study. The dose-escalation stage is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and following repeat doses of JMT103 given every 4 weeks (Q4W) for three times. The expansion study stage is designed to evaluate the safety, tolerability, and pharmacokinetics of repeat doses of JMT103 given every 4 weeks (Q4W) for three times.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huiping Li, MD; Phone Number: 86-10-88196827; Email: huipingli2012@hotmail.com
• Study Contact Backup: Name: Shukui Qin, MD; Phone Number: 86-25-84453932; Email: qinsk@csco.org.cn

Study Locations

• China
  • Shanghai, China, 200123
    • Recruiting
    • Shanghai East Hospital
    • Contact: Jin Li, MD; Phone Number: 86-21-38804518; Email: lijin@csco.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histologically or cytologically confirmed malignant solid tumors;
• imaging examination shows at least one site with bone metastases from tumors;
• ECOG performance status of score 0 or 1;
• Expected survival time ≥ 7.5 months.

Exclusion Criteria:

• Previous or present osteomyelitis or osteonecrosis of the jaw; unhealed dental or oral surgery wounds; acute disease of the tooth or jaw requiring oral surgery; and invasive dental surgery planned to be received during the study;
• It is planned to perform therapeutic radiotherapy or orthopedic surgery for patients during the study;
• Known active brain metastases or leptomeningeal metastases. The subjects with neurological symptoms should receive brain CT/MRI to ensure that there have no metastases;
• Patients with bone metabolic diseases (Paget's disease, Cushing syndrome and hyperprolactinemia), rheumatoid arthritis, and current hyperparathyroidism or parathyroid dysfunction;
• Uncontrolled complications
• Active bacterial or fungal infections requiring systematic treatment within 7 days before the screening;
• Patients with HIV infections or active hepatitis;
• Pregnancy (positive serum β-HCG result) or lactation;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-RANKL Monoclonal Antibody; Anti-RANKL Monoclonal Antibody is to be injected subcutaneously 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg or 3.0 mg/kg.	Biological: Anti-RANKL Monoclonal Antibody; JMT103 is recombinant fully human anti-RANKL monoclonal antibody. JMT103 is provided as the injection,120 mg/vial. JMT103 was administered subcutaneously in the upper arm, upper thigh, or abdomen.; Other Names: JMT103

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti-Drug Antibody of Anti-RANKL Monoclonal Antibody (JMT103) in Patients With Bone Metastases From Tumors	225 days in escalation study stage, and 141 days in expansion study stage
Maximum serum Concentration (Cmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Peak Time (Tmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Area Under the Curve (AUC) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Terminal t1/2 after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Serum clearance (CL) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Apparent volume of distribution (V) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Minimum serum Concentration (Cmin) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Minimum serum Concentration (Cmin) after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	141 days
Apparent volume of distribution after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	141 days
Cumulative factor after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	141 days
Percent changes of serum C-terminal telopeptide of type 1 collagen after single dose of JMT103	85 days
Percent changes of bone alkaline phosphatase after single dose of JMT103	85 days
Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	85 days
Percent changes of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) after multiple doses of JMT103	141 days
Percent changes of serum C-terminal telopeptide of type 1 collagen after multiple doses of JMT103	141 days
Percent changes of bone alkaline phosphatase after multiple doses of JMT103	141 days
Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after multiple doses of JMT103	141 days
Percent changes of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)	141 days

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.
• Collaborators: Quintiles, Inc.; Covance; KingMed Diagnostics
• Investigators: Principal Investigator: Jin Li, MD, Shanghai East Hospital

Publications and helpful links

General Publications

• Liang X, Xue J, Ge X, Li J, Li H, Xue L, Di L, Tang W, Song G, Li Q, Jiang H, Zhao W, Lin F, Shao B, Yang X, Wu Z, Zhang T, Wang C, Guo Y. Safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors. Front Oncol. 2022 Aug 5;12:971594. doi: 10.3389/fonc.2022.971594. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Anticipated): August 30, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: May 27, 2018
• First Posted (Actual): June 8, 2018

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: May 27, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: JMT103 in Patients with Bone Metastases from Tumors
• 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; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: JMT103CN01

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