Phase 1 Trial of a Fully Human Monoclonal Antibody of Receptor Activator for Nuclear Factor-κ B Ligand (RNAKL, TK006) Safety, Pharmacokinetics, and Pharmacodynamics in Patients With Breast Cancer-related Bone Metastases

Jiangsu T-Mab Biopharma Co.,Ltd1 site in 1 country40 target enrollmentJuly 20, 2017

ConditionsBreast Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Breast Cancer
Sponsor: Jiangsu T-Mab Biopharma Co.,Ltd
Enrollment: 40
Locations: 1
Primary Endpoint: Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to TK006 assessed by CTCAE v4.03
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single and multiple subcutaneous injection TK006 in patients with breast cancer-related bone metastases.

Detailed Description

This is an single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single and multiple subcutaneous injection TK006 in patients with breast cancer-related bone metastases. It contains 4 cohorts：60 mg single-dose conhort, 120 mg single-dose conhort, 180 mg single-dose conhort and 120 mg Q4W （one dose every 4 weeks, 3 dose totally） conhort.

Registry

clinicaltrials.gov

Start Date

July 20, 2017

End Date

August 2018

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Jiangsu T-Mab Biopharma Co.,Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients provide written informed consent voluntarily；
•18\~65 years old；
•Patients with pathology confirmed breast cancer radiological evidence with bone metastasis；
•Eastern Cooperative Oncology Group(ECOG) performance status≤2
•Anticipated life span≥6-month；
•Adequate reservation of hematopoiesis, liver and kidney functions:
•Absolute neutrophil count (ANC) ≥1.5×10\^9/L
•Absolute platelet count (PLT) ≥100×10\^9/L
•Hemoglobin (Hb) ≥90 g/L
•Total bilirubin (TBIL) ≤1.0 time the upper limit of normal (ULN)

Exclusion Criteria

•Hypersensitivity to any investigational medicine or supplements in this study.
•Women in Pregnancy or nursing.
•Anti-human immunodeficiency virus (HIV) antibody positive.
•Patients with hepatitis B virus DNA ≥10\^5 copies/mL or active hepatitis C would not be selected. Stable hepatitis B or hepatitis C defined as AST/ALT≤2 ULN will not be selected as well if patients are not treated with antiviral therapy while receving immunosuppressive therapy or chemotherapy meanwhile.
•Prior malignancies (excluding the targeted breast cancer, basal cell carcinoma, or cervical cancer in situ) within 3 years.
•Uncontrolled systemic diseases, or organic or mental disorders that could affect compliance.
•Central nervous system metastasis that is symptomatic or require treatment.
•Unresolved toxicities ≥2 grades from previous chemo-therapy (excluding alopecia).
•Major surgery of bone or trauma within 4 weeks before the first dosing.
•Fracture of long bone within 90-day before the first dosing.

Outcomes

Primary Outcomes

Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to TK006 assessed by CTCAE v4.03

Time Frame: single dose cohort：112 days, multiple dose cohort：140 days

Collect the information of AEs and SAEs, vital sign, physical examination, laboratory examination and electrocardiogram during the trial.

Secondary Outcomes

bioavailability corrected apparent volume of distribution [Vd/F](single dose cohort：112 days, multiple dose cohort：140 days)
Maximum observed maximum plasma concentration [Cmax](single dose cohort：112 days, multiple dose cohort：140 days)
Time to reach the maximum observed plasma concentration [Tmax](single dose cohort：112 days, multiple dose cohort：140 days)
Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast](single dose cohort：112 days, multiple dose cohort：140 days)
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf](single dose cohort：112 days, multiple dose cohort：140 days)
Terminal elimination half-life[T1/2](single dose cohort：112 days, multiple dose cohort：140 days)
bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F](single dose cohort：112 days, multiple dose cohort：140 days)
urine creatinine corrected cross-linked N-telopeptides of type I collagen [uNTX/Cr](single dose cohort：112 days, multiple dose cohort：140 days)
serum bone alkaline phosphatase [bALP](single dose cohort：112 days, multiple dose cohort：140 days)
anti-drug antibody [ADA](single dose cohort：112 days, multiple dose cohort：140 days)