Clinical trial NCT03550508: Safety, Tolerability and PK/PD of JMT103 in Patients With Bone Metastases From Tumors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Bone Metastases
Keywords: JMT103 in Patients with Bone Metastases from Tumors
Lead sponsor: Shanghai JMT-Bio Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
name: Covance
name: KingMed Diagnostics
First posted: 2018-06-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The accelerated titration and traditional "3+3" dose-escalation designs are applied in this study.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 28 days
Secondary outcomes:
measure: Anti-Drug Antibody of Anti-RANKL Monoclonal Antibody (JMT103) in Patients With Bone Metastases From Tumors
timeFrame: 225 days in escalation study stage, and 141 days in expansion study stage
measure: Maximum serum Concentration (Cmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Peak Time (Tmax) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Area Under the Curve (AUC) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Terminal t1/2 after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Serum clearance (CL) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Apparent volume of distribution (V) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Minimum serum Concentration (Cmin) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Minimum serum Concentration (Cmin) after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 141 days
measure: Apparent volume of distribution after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 141 days
measure: Cumulative factor after multiple dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 141 days
measure: Percent changes of serum C-terminal telopeptide of type 1 collagen after single dose of JMT103
timeFrame: 85 days
measure: Percent changes of bone alkaline phosphatase after single dose of JMT103
timeFrame: 85 days
measure: Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after single dose injection of Anti-RANKL Monoclonal Antibody (JMT103)
timeFrame: 85 days
measure: Percent changes of urinary N-terminal telopeptide of type 1 collagen/creatine (U-NTX/Cr) after multiple doses of JMT103
timeFrame: 141 days
measure: Percent changes of serum C-terminal telopeptide of type 1 collagen after multiple doses of JMT103
timeFrame: 141 days
measure: Percent changes of bone alkaline phosphatase after multiple doses of JMT103
timeFrame: 141 days
measure: Percent changes of procollagen type 1 N-peptide, tartrate-resistant acid phosphatase 5b (TRAP5b) after multiple doses of JMT103
timeFrame: 141 days
measure: 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)
timeFrame: 141 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.