Assessment of Anti-RANKL Antibody in Post-menopausal Women

March 13, 2018 updated by: Jiangsu T-Mab Biopharma Co.,Ltd

Phase I Trial of Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Fully Human Monoclonal Antibody to RANKL (TK006) in Post-menopausal Women.

This is a single-center, open-label, dose-escalating study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL) (code name: TK006) in postmenopausal women.

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 a phase I, open-label, single-dose, dose escalation study in postmenopausal women conducted at single center.

The objectives are to assess the safety and tolerability, effects on bone turnover measured by biochemical markers and bone density, and the pharmacokinetics and immunogenicity of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL), (code name: TK006).

Subjects would sequentially enroll in one of three cohorts. Subjects in the first cohort would receive a single 30-mg subcutaneous injection of TK006. If no safety signals are observed in the first cohort after 28 days, subjects would enroll in the second cohort and receive a single 60-mg subcutaneous injection of TK006. After an 28-day period for observation of safety of the second dose, subjects would enroll in the third cohort and receive a single 120-mg subcutaneous injection of TK006.

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.
24

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
    • Beijing
      • Beijing, Beijing, China
        • Peking Union Medical College Hospital

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

No older than 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Subjects who provide informed consent voluntarily;
  2. Women who are postmenopausal defined as being amenorrheic for at least 24-month, and follicule-stimulating hormone (FSH)>40 U/L, estradiol (E2)<110pmol/L (or <30pg/mL) as well;
  3. ≤65 years old, with no restricted activity.

Exclusion Criteria:

  1. Known hypersensitivity to similar medicines or other products derived from mammalian cells, or medical history of severe allergic to foods or medicines;
  2. Treatment with diphosphonate or fluoride, oestrogen, selective estrogen receptor modulators, calcitonin, parathyroid hormone, high dose Vitamin D (≥1000 IU/day), anabolic steroids, systemic glucocorticoids within 12-month before dosing, or administered with calcitriol within 6 months before dosing;
  3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.0 times the upper limit of normal (ULN), or alkaline phosphatase (ALP)>1.5×ULN, or Total bilirubin (TBIL) >1.5×ULN, creatinine clearance rate<60 mL/min;
  4. Disorders that could affect the study outcomes, such as osteomalacia, dysostosis, Paget's disease, Cushing syndrome, hyperprolactinemia, rheumatoid arthritis, hyperparathyroidism, hypoparathyroidism, or other diseases that could affect bone metabolism;

  5. Hyperthyroidism or hypothyroidism, unless hypothyroidism patients are receiving regular treatment with thyroid hormone and:

    • Thyroid stimulating hormone (TSH) is normal, or
    • TSH>4.78μIU/Ml, ≤10.0μIU/mL and thyroxine (T4) is normal.
  6. Malabsorption syndrome or other disorders that could affect intestinal absorption function, such as Crohn's disease, chronic pancreatitis, etc;
  7. Hepatocirrhosis or severe liver disease (defined as ascites, hepatic encepalopathy, coagulation disorder, hypoalbuminemia, Esophagus and fundus gastricus varication, persistent jaundice), known diseases of biliary tract (excluding Gilbert syndrome and Asymptomatic gallstone);
  8. Past or currently suffering from mandibular osteomyelitis or osteonecrosis, or any fracture within 6 months prior to first dosing; or suffering from acute tooth or mandibular disease that require tooth extracting, dental implanting or other invasive surgery; or had the above operation within 1-month before first dosing; or unhealing wound of oral surgery;
  9. HBsAg positive, or anti-HCV antibody positive, or anti-HIV antibody positive, or anti-Syphilis antibody positive;
  10. Prior malignancies (excluding the targeted breast cancer, basal cell carcinoma, or cervical cancer in situ) within 5 years (excluding completely resected Basal cell or squamous-cell carcinoma in situ, cervical carcinoma and Breast ductal carcinoma；
  11. A variety of diseases that affect the ability of the subject to sign informed consent or follow the steps of the study; or suffer from various physical or mental illnesses that the investigators consider to affect the subject's successful completion of the study or may interfere with the interpretation of the findings;
  12. Albumin-adjusted calcium≥2.0mmol/L, ≤2.9mmol/ L(Calcium supplements are not allowed within 8 hours before examination);
  13. Subjects with fracture high risk and requiring treatment;
  14. 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.
  15. 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 Assignment
  • Masking: None (Open Label)

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: 30 mg single dose cohort
Subjects would receive a 30 mg single dose of TK006.
Biological: TK006
Subcutaneous injection
Other Names:
  • fully human monoclonal anti-RANKL antibody
Experimental: 60 mg single dose cohort
Subjects 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
Subjects would receive a 120 mg single dose of TK006.
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
Incidence of adverse events （AEs）
Time Frame: Up to 252 days.
Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.
Up to 252 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: Up to 252 days.
Calculated by the linear trapezoidal method.
Up to 252 days.
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
Time Frame: Up to 252 days.
Calculated by the linear trapezoidal and extrapolation method.
Up to 252 days.
Maximum observed maximum plasma concentration [Cmax]
Time Frame: Up to 252 days.
The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.
Up to 252 days.
Time to reach the maximum observed plasma concentration [Tmax]
Time Frame: Up to 252 days.
The time at which the Cmax is observed.
Up to 252 days.
Terminal elimination half-life[T1/2]
Time Frame: Up to 252 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.
Up to 252 days.
Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]
Time Frame: Up to 252 days.
The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞
Up to 252 days.
Bioavailability corrected apparent volume of distribution [Vd/F]
Time Frame: Up to 252 days.
Apparent volume of distribution based on the terminal elimination phase.
Up to 252 days.
Serum type I collagen cross-link C telopeptide (sNTX)
Time Frame: Up to 252 days.
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Up to 252 days.
serum bone alkaline phosphatase [bALP]
Time Frame: Up to 252 days.
Would be assessed at week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Up to 252 days.
Intact Parathyroid Hormone (iPTH)
Time Frame: Up to 252 days.
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Up to 252 days.
Bone density of lumbar vertebra and collum femoris
Time Frame: Up to 252 days.
Assessed by Dual energy X-ray (DXA) bone density measurement at week 8,16, 24 and 36.
Up to 252 days.
anti-drug antibody [ADA]
Time Frame: Up to 252 days.
Assessed at day 0（pre-dosing）, week 4, 12, 24 and 36.
Up to 252 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.
August 7, 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.
December 30, 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.
December 30, 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).
August 3, 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 3, 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 8, 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.
March 14, 2018

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.
March 13, 2018

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.
March 1, 2018

More Information

Terms related to this study

Keywords

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.
  • TK006-101

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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