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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Bone Metastases

Intervention / Treatment
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* Biological: Anti-RANKL Monoclonal Antibody


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The accelerated titration and traditional 3+3 dose-escalation designs are applied in this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-RANKL Monoclonal Antibody<br>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<br>* 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.<br>* Other names: JMT103;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JMT103 in Patients with Bone Metastases from Tumors