KN015,the active substance recombinant human Follicle Stimulating Hormone(FSH) Fc fusion protein, which belongs to the pharmaceutical class gonadotropins.KN015 is proposed for Assisted Reproductive Technology (ART) programs only. Its indication is Controlled Ovarian Stimulation (COS)in combination with a gonadotropin releasing hormone (GnRH) antagonist for the development of multiple follicles in women participating in an ART program. Due to its prolonged duration of FSH activity compared to conventional recombinant FSH (rFSH), a single subcutaneous injection of the recommended dose of KN015 may replace any daily rFSH preparation in a COS treatment cycle. This study is to evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of KN015 in healthy Chinese female subjects.
This is a phase I, randomized, placebo-controlled, single ascending dose, double blind parallel design, first-in-human study. The study design allows a gradual escalation of the dose-level with intensive safety monitoring to ensure the safety of the subjects. Dose escalation will continue until identification of MTD or up to a maximum dose of 100 μg. Tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity characteristics of KN015 will be assessed in healthy female subjects. Eligible subjects will undergo down-regulation of endogenous FSH with a GnRH antagonist Triptorelin prior to receiving KN015.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
50
experimental drug
Comparator.
The drug is used for down-regulation of endogenous FSH.
The First Hospital of Jilin University
Chuangchun, Jilin, China
RECRUITINGNumber of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(SAEs) and AEs of special interest.
Time frame: From screening to up to 36 days
Maximum observed serum concentration (Cmax) of KN015 in healthy Chinese female subjects
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Time of Maximum observed serum concentration (Tmax) of KN015 in healthy Chinese female subjects.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Adjusted geometric means of area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUC(0-T)) for KN015.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Adjusted geometric means of area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for KN015.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Serum Half-life (T-HALF) of KN015 in healthy Chinese female subjects.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Serum clearance (CL) of KN015 in healthy Chinese female subjects.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
Volume of distribution at steady state (VSS) of KN015 in healthy Chinese female subjects.
Time frame: within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.
The number of follicles after dosing.
Time frame: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose
The size of follicles after dosing.
Time frame: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose
Determination of serum concentrations of FSH, E2, LH and P after dosing.
Time frame: From screening to up to 36 days
Percentage of participants with anti-KN015 antibody.
Time frame: -1,8,15,36 days post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.