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

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ClinicalTrials.gov Identifier: NCT03239756
Recruitment Status : Recruiting
First Posted : August 4, 2017
Last Update Posted : August 23, 2017
Sponsor:
Information provided by (Responsible Party):
Jiangsu T-Mab Biopharma Co.,Ltd

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: TK006 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 20, 2017
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 60 mg single dose cohort
patients would receive a 60 mg single dose of TK006.
Biological: TK006
Subcutaneous injection
Other Name: 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 Name: 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 Name: 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 Name: fully human monoclonal anti-RANKL antibody




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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-∞

  7. 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.

  8. 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.


  9. 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.

  10. 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.




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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03239756


Contacts
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Contact: Yu M X 15021830072 yumingxia@sh-qingfeng.net
Contact: Jiang H B 13062892252 jianghaibiao@sh-qingfeng.net

Locations
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China, Jiangsu
the first affiliated hospital with Nanjing University Recruiting
Nanjing, Jiangsu, China, 210029
Contact: Yin Y M    13951842727    ym.yin@hotmail.com   
Sponsors and Collaborators
Jiangsu T-Mab Biopharma Co.,Ltd
Investigators
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Study Director: Jiang H Y Jiangsu T-Mab Biopharma Co.,Ltd

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Responsible Party: Jiangsu T-Mab Biopharma Co.,Ltd
ClinicalTrials.gov Identifier: NCT03239756     History of Changes
Other Study ID Numbers: Tmab-TK006-102
First Posted: August 4, 2017    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs