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

Bone Metastases Clinical Trial

— JMT103  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03550508
• Other study ID #: JMT103CN01
• Status: Recruiting
• Phase: Phase 1
• Start date: May 21, 2018
• Est. completion date: December 1, 2019

Study information

• Verified date: May 2018
• Source: Shanghai JMT-Bio Inc.
• Contact: Huiping Li, MD
• Phone: 86-10-88196827
• Email: huipingli2012[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 1, 2019
• Est. primary completion date: August 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ß-HCG result) or lactation;

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases
• Bone Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

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.

Locations

Country	Name	City	State
China	Shanghai East Hospital	Shanghai

Sponsors (4)

Lead Sponsor	Collaborator
Shanghai JMT-Bio Inc.	Covance, KingMed Diagnostics, Quintiles, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03		28 days
Secondary	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
Secondary	Maximum serum Concentration (Cmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Peak Time (Tmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Area Under the Curve (AUC) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Terminal t1/2 after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Serum clearance (CL) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Apparent volume of distribution (V) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Minimum serum Concentration (Cmin) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		85 days
Secondary	Minimum serum Concentration (Cmin) after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		141 days
Secondary	Apparent volume of distribution after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		141 days
Secondary	Cumulative factor after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)		141 days
Secondary	Percent changes of serum C-terminal telopeptide of type 1 collagen after single dose of JMT103		85 days
Secondary	Percent changes of bone alkaline phosphatase after single dose of JMT103		85 days
Secondary	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
Secondary	Percent changes of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) after multiple doses of JMT103		141 days
Secondary	Percent changes of serum C-terminal telopeptide of type 1 collagen after multiple doses of JMT103		141 days
Secondary	Percent changes of bone alkaline phosphatase after multiple doses of JMT103		141 days
Secondary	Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after multiple doses of JMT103		141 days
Secondary	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