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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Subcutaneous injection
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Incidence of adverse events (AEs)
Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.
Time frame: Up to 252 days.
Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]
Calculated by the linear trapezoidal method.
Time frame: Up to 252 days.
Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
Calculated by the linear trapezoidal and extrapolation method.
Time frame: Up to 252 days.
Maximum observed maximum plasma concentration [Cmax]
The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.
Time frame: Up to 252 days.
Time to reach the maximum observed plasma concentration [Tmax]
The time at which the Cmax is observed.
Time frame: Up to 252 days.
Terminal elimination half-life[T1/2]
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.
Time frame: Up to 252 days.
Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]
The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞
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Time frame: Up to 252 days.
Bioavailability corrected apparent volume of distribution [Vd/F]
Apparent volume of distribution based on the terminal elimination phase.
Time frame: Up to 252 days.
Serum type I collagen cross-link C telopeptide (sNTX)
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Time frame: Up to 252 days.
serum bone alkaline phosphatase [bALP]
Would be assessed at week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Time frame: Up to 252 days.
Intact Parathyroid Hormone (iPTH)
Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
Time frame: Up to 252 days.
Bone density of lumbar vertebra and collum femoris
Assessed by Dual energy X-ray (DXA) bone density measurement at week 8,16, 24 and 36.
Time frame: Up to 252 days.
anti-drug antibody [ADA]
Assessed at day 0(pre-dosing), week 4, 12, 24 and 36.
Time frame: Up to 252 days.