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

Primary Purpose

Bone Metastases

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Anti-RANKL Monoclonal Antibody
Sponsored by
Shanghai JMT-Bio Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bone Metastases focused on measuring JMT103 in Patients with Bone Metastases from Tumors

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Shanghai East HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anti-RANKL Monoclonal Antibody

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
April 18, 2018
Last Updated
May 27, 2018
Sponsor
Shanghai JMT-Bio Inc.
Collaborators
Quintiles, Inc., Covance, KingMed Diagnostics
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1. Study Identification

Unique Protocol Identification Number
NCT03550508
Brief Title
Safety, Tolerability and PK/PD of JMT103 in Patients With Bone Metastases From Tumors
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 21, 2018 (Actual)
Primary Completion Date
August 30, 2019 (Anticipated)
Study Completion Date
December 1, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai JMT-Bio Inc.
Collaborators
Quintiles, Inc., Covance, KingMed Diagnostics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Metastases
Keywords
JMT103 in Patients with Bone Metastases from Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
The accelerated titration and traditional "3+3" dose-escalation designs are applied in this study.
Masking
None (Open Label)
Masking Description
Open
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huiping Li, MD
Phone
86-10-88196827
Email
huipingli2012@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Shukui Qin, MD
Phone
86-25-84453932
Email
qinsk@csco.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Li, MD
Organizational Affiliation
Shanghai East Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai East Hospital
City
Shanghai
ZIP/Postal Code
200123
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Li, MD
Phone
86-21-38804518
Email
lijin@csco.org.cn

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35992822
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.
Results Reference
derived

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

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