Assessment of TK006 in Patients With Breast Cancer-related Bone Metastases

August 21, 2017 updated by: Jiangsu T-Mab Biopharma Co.,Ltd

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • The First Affiliated Hospital With Nanjing University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients provide written informed consent voluntarily；
  2. 18~65 years old；
  3. Patients with pathology confirmed breast cancer radiological evidence with bone metastasis；
  4. Eastern Cooperative Oncology Group(ECOG) performance status≤2
  5. Anticipated life span≥6-month；

  6. 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)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0 ULN
    • Serum creatinine (sCr) ≤2.0 ULN
  7. Albumin-adjusted calcium≥2.0 mmol/L, ≤2.9 mmol/ L(Calcium supplements are not allowed within 8 hours before examination).

Exclusion Criteria:

  1. Hypersensitivity to any investigational medicine or supplements in this study.
  2. Women in Pregnancy or nursing.
  3. Anti-human immunodeficiency virus (HIV) antibody positive.
  4. 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.
  5. Prior malignancies (excluding the targeted breast cancer, basal cell carcinoma, or cervical cancer in situ) within 3 years.
  6. Uncontrolled systemic diseases, or organic or mental disorders that could affect compliance.
  7. Central nervous system metastasis that is symptomatic or require treatment.
  8. Unresolved toxicities ≥2 grades from previous chemo-therapy (excluding alopecia).
  9. Major surgery of bone or trauma within 4 weeks before the first dosing.
  10. Fracture of long bone within 90-day before the first dosing.
  11. Radiation therapy to bone within 2 weeks or treatment with radioisotopes within 8 weeks before the first dosing.
  12. Treatment with diphosphonate within 30-day or administration of calcitonin, parathyroid hormone-related peptides, mithramycin, gallium nitrate or strontium ranelate within 6-month before the first dosing. Plan to receive systemic treatment with glucocorticosteroids over a long period during the trial.
  13. Hyperthyroidism or hypothyroidism, unless hypothyroidism patients are receiving regular treatment with thyroid hormone and:

1) Thyroid stimulating hormone (TSH) is normal, or 2) TSH>4.78μIU/Ml, ≤10.0μIU/mL and thyroxine (T4) is normal. 14. Disorders of hypoparathyroidism or hyperparathyroidism, osteomalacia, rheumatoid arthritis, acute attack of osteoarthritis, gout, Paget's disease, malabsorption syndrome, ascites, or other diseases that could affect bone metabolism.

15. Previous or existing osteomyelitis or osteonecrosis of jaw, odontia or jaw diseases which are in active or require invasive operations, unhealing wound of oral surgery, or planned invasive dental operations during this trial.

16. Has been selected for the study of other test devices or test drugs, or the duration of the clinical studies that have taken less than 30 days or 5 half-lives or biological effects, whichever is longer.

17. Other situations which are not suitable for participation judged by the principal investigator (PI).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 60 mg single dose cohort
patients would receive a 60 mg single dose of TK006.
Biological: TK006
Subcutaneous injection
Other Names:
  • fully human monoclonal anti-RANKL antibody
EXPERIMENTAL: 120 mg single dose cohort
patients would receive a 120 mg single dose of TK006.
Biological: TK006
Subcutaneous injection
Other Names:
  • fully human monoclonal anti-RANKL antibody
EXPERIMENTAL: 180 mg single dose cohort
patients would receive a 180 mg single dose of TK006.
Biological: TK006
Subcutaneous injection
Other Names:
  • fully human monoclonal anti-RANKL antibody
EXPERIMENTAL: 120 mg Q4W cohort
patients would receive 120 mg TK006 every 4 weeks, for a total of 3 doses.
Biological: TK006
Subcutaneous injection
Other Names:
  • fully human monoclonal anti-RANKL antibody

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
single dose cohort：112 days, multiple dose cohort：140 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
Calculated by the linear trapezoidal method.
single dose cohort：112 days, multiple dose cohort：140 days
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
Calculated by the linear trapezoidal and extrapolation method.
single dose cohort：112 days, multiple dose cohort：140 days
Maximum observed maximum plasma concentration [Cmax]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.
single dose cohort：112 days, multiple dose cohort：140 days
Time to reach the maximum observed plasma concentration [Tmax]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
The time at which the Cmax is observed.
single dose cohort：112 days, multiple dose cohort：140 days
Terminal elimination half-life[T1/2]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
The time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
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]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞
single dose cohort：112 days, multiple dose cohort：140 days
bioavailability corrected apparent volume of distribution [Vd/F]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
Apparent volume of distribution based on the terminal elimination phase.
single dose cohort：112 days, multiple dose cohort：140 days
urine creatinine corrected cross-linked N-telopeptides of type I collagen [uNTX/Cr]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days

For singel dose cohort, detecting the level of uNTX at screening period, day 0 (before dosing)、day 1, day 7, day 14, day 28, day 56, day 84 and day 112 For multiple dose cohort：detecting the level of uNTX at screening period, day 0 (before dosing)、day 1, day 7, day 14, day 28 (before dosing), day 56 (before dosing), day 84 and day 140.

Assessing the change of uNTX level to baseline and the uNTX should be corrected by urine creatinine.
single dose cohort：112 days, multiple dose cohort：140 days
serum bone alkaline phosphatase [bALP]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days
Assessing the change of serum bALP level to baseline. For singel dose cohort, detecting the level of uNTX at screening period, day 0 (before dosing)、day 1, day 7, day 14, day 28, day 56, day 84 and day 112 For multiple dose cohort：detecting the level of uNTX at screening period, day 0 (before dosing)、day 1, day 7, day 14, day 28 (before dosing), day 56 (before dosing), day 84 and day 140.
single dose cohort：112 days, multiple dose cohort：140 days
anti-drug antibody [ADA]
Time Frame: single dose cohort：112 days, multiple dose cohort：140 days

Quantitative assay the ADA. For single cohort, the ADA titer would be detected at day 0 (before dosing) and day 56.

For multiple dose cohort, the ADA titer would be detected at day 0 (before dosing), day 28 (before dosing), day 56 (before dosing), day 84 and day 140.
single dose cohort：112 days, multiple dose cohort：140 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jiangsu T-Mab Biopharma Co.,Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 20, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2018

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 28, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 23, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Tmab-TK006-102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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