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

Shanghai JMT-Bio Inc.36 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bone Metastases

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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;

Outcomes

Primary Outcomes

Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

Time frame: 28 days

Secondary Outcomes

Anti-Drug Antibody of Anti-RANKL Monoclonal Antibody (JMT103) in Patients With Bone Metastases From Tumors

Time frame: 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)

Time frame: 85 days

Peak Time (Tmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Area Under the Curve (AUC) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Terminal t1/2 after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Serum clearance (CL) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Apparent volume of distribution (V) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Minimum serum Concentration (Cmin) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 85 days

Minimum serum Concentration (Cmin) after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 141 days

Apparent volume of distribution after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 141 days

Cumulative factor after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)

Time frame: 141 days

Percent changes of serum C-terminal telopeptide of type 1 collagen after single dose of JMT103

Time frame: 85 days

Percent changes of bone alkaline phosphatase after single dose of JMT103

Time frame: 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)

Time frame: 85 days

Percent changes of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) after multiple doses of JMT103

Time frame: 141 days

Percent changes of serum C-terminal telopeptide of type 1 collagen after multiple doses of JMT103

Time frame: 141 days

Percent changes of bone alkaline phosphatase after multiple doses of JMT103

Time frame: 141 days

Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after multiple doses of JMT103

Time frame: 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)

Time frame: 141 days

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts