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

NCT ID: NCT03550508

Last Updated: 2018-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-21
• Study Completion Date: 2019-12-01

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.

Conditions

Bone Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anti-RANKL Monoclonal Antibody

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.

Group Type: EXPERIMENTAL

Anti-RANKL Monoclonal Antibody

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

JMT103

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Covance

INDUSTRY

Sponsor Role: collaborator

KingMed Diagnostics

UNKNOWN

Sponsor Role: collaborator

Shanghai JMT-Bio Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Li, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai East Hospital

Locations

Shanghai East Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Huiping Li, MD

Role: CONTACT

huipingli2012@hotmail.com

86-10-88196827

Shukui Qin, MD

Role: CONTACT

qinsk@csco.org.cn

86-25-84453932

Facility Contacts

Jin Li, MD

Role: primary

lijin@csco.org.cn

86-21-38804518

References

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.

Reference Type: DERIVED

PMID: 35992822 (View on PubMed)

Other Identifiers

JMT103CN01

Identifier Type: -

Identifier Source: org_study_id