This trial is a single center, randomized, double-blind, placebo-controlled dose escalation study aimed at examining the safety, tolerability, and pharmacokinetics/pharmacodynamics of single and multiple injections of RAB001 in healthy subjects. According to the results of Phase I clinical trials abroad, two dose groups (400 μ g/kg and 750 μ g/kg) were established, with 8 healthy subjects enrolled in each dose group (6 in the experimental group and 2 in the placebo group), for a total of 16 healthy subjects. Each dose group is divided into two stages. Phase 1: Single dose administration phase Subjects who meet the inclusion criteria will first undergo a single dose study in the 400 μ g/kg dose group. Blood samples will be collected at predetermined time points for single dose PK, PD, and immunogenicity evaluation. After the single dose, safety and tolerance data will be collected for 14 days. If the subjects are tolerant, a single dose study in the 750 μ g/kg dose group can be conducted. After the dose increases to the maximum dose of 750 μ g/kg as designed in this experiment, the next dose will not be administered. Phase 2: Multiple administration phase Single dose administration is combined with multiple dose administration. If the subjects can tolerate it during the single dose phase, they will enter the multiple dose study phase, which will be administered once every 2 weeks, on days 15, 29, and 43 respectively. Collect blood samples at predetermined time points for PK, PD, and immunogenicity evaluation, observe for 14 days after the last administration, and collect safety and tolerability data. This experiment adopts a step-by-step increasing method for dose escalation, and the next dose group must complete the safety and tolerability evaluation of a single dose in the previous dose group before starting. Each subject only receives one corresponding dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE
Enrollment
16
The subjects received intravenous administration of RAB001 400 μ g/kg on day 1、15、29、43
The subjects received intravenous administration of RAB001 750 μ g/kg on day 1、15、29、43
The subjects received intravenous administration of normal saline on day 1、15、29、43
Hebei University Affiliated Hospital
Baoding, Hebei, China
Adverse events
Adverse events,evaluate the safety of single injections of RAB001 at different doses
Time frame: 14 days after single injections
Serious adverse events
serious adverse events during the study
Time frame: 14 days after single administration
Adverse events
Adverse events evaluate the safety and tolerability of multiple injections of RAB001 at different doses
Time frame: 14 days after multiple administrations
Serious adverse events
Serious adverse events during the study,evaluate the safety of multiple injections of RAB001 at different doses
Time frame: 14 days after multiple administrations
PK parameter Cmax
PK parameter Cmax :Maximum peak plasma concentration (Cmax)
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15
PK parameter AUC0-t
PK parameter AUC0-t:Area under the concentration-time curve (AUC0-t) from time zero to time "t" .
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter AUC0-∞
PK parameter AUC0-∞:AUC from time zero to infinity (AUC0-∞) .
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter Tmax
PK parameter Tmax.Time of Cmax (Tmax).
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter T1/2z
PK parameter T1/2z:Terminal-phase elimination half-life (t1/2) .
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter-Vz/F
PK parameter-Vz/F:Apparent Volume of Distribution During the Terminal Phase (Vz/F) of RAB001 in Plasma
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter-CL
PK parameter-CL:Systemic Clearance (CL) of RAB001
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK parameter λz
PK parameter λz:Apparent Terminal Elimination Rate Constant (λZ) of
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
PK Parameter: CLss
PK Parameter: CLss , the apparent systemic clearance from plasma observed during a dosing interval at steady state following extravascular administration
Time frame: The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.
Bone turnover marker: BALP
Change in Serum Bone Alkaline Phosphatase (BALP) Level
Time frame: Day 1、8 、15、29、43 、 57
Bone turnover marker: PINP levels
PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels
Time frame: Day 1、8 、15、29、43 、57
Bone turnover marker: Osteocalcin (OC) Levels
the bone turnover marker : Osteocalcin (OC) Levels
Time frame: Day 1、8 、15、29、43 、 57
Bone turnover marker:CTX-I Levels
CTX-I (C-terminal Telopeptide of Type I Collagen )Levels the bone turnover marker
Time frame: Day 1、8 、15、29、43 、57
Bone turnover marker: VEGF
Bone turnover marker: VEGF vascular endothelial growth factor
Time frame: Day 1、8 、15、29、43、57
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