Osteonecrosis of the Femoral Head
Conditions
Keywords
Osteonecrosis
Brief summary
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.
Interventions
DRUGRAB001 400 μg/kg group
The subjects received intravenous administration of RAB001 400 μ g/kg on day 1、15、29、43
DRUGRAB001 750 μg/kg group
The subjects received intravenous administration of RAB001 750 μ g/kg on day 1、15、29、43
DRUGNormal saline
The subjects received intravenous administration of normal saline on day 1、15、29、43
Sponsors
ZhongShan LaiBo RuiChen BioMedicine Co.,Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Male body weight should be at least 50.0 kg, female body weight should be at least 45 kg; body mass index (BMI) should be between 19.0-26.0 kg/m2 (including boundary values); * Can understand the informed consent form, voluntarily participate and sign the informed consent form; * Capable of completing experiments in accordance with the research protocol.
Exclusion criteria
1. During the screening period, vital signs, physical examination, 12 lead electrocardiogram examination, and laboratory tests (including blood routine, urine routine, blood biochemistry, and coagulation function) were determined by the researchers to be clinically significant abnormalities; 2. Suffering from the blood system, circulatory system, and digestive system Individuals with a history of serious clinical diseases such as systemic, urinary, respiratory, nervous, immune, endocrine, malignant tumors, mental disorders, and metabolic abnormalities, or any other diseases or physiological conditions that can interfere with test results; 3. Individuals with a significant history of allergic reactions in clinical practice, especially drug allergies, or those known to be allergic to this product; 4. Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody and treponema pallidum (TP) antibody test, any of which is positive; 5. Individuals with positive urine screening for drug abuse (including morphine, methamphetamine, ketamine, methylenedioxymethamphetamine, tetrahydrocannabinol); 6. Individuals with a history of drug use or substance abuse (including the use of prohibited substances for medical use and controlled drugs); 7. Screening for those who have undergone critical surgery within the previous 3 months or plan to undergo surgery during the trial period, as well as those who have undergone surgery that may affect drug absorption, distribution, metabolism, and excretion; 8. Screening participants who have participated in any clinical trial as subjects within the first 3 months; 9. Individuals who have donated blood or lost blood/plasma greater than 400 mL within the first 3 months of screening (excluding female physiological bleeding); 10. Alcoholics (i.e. males drinking more than 28 standard units of alcohol per week and females drinking more than 21 standard units of alcohol per week, with 1 standard unit containing 14 g of alcohol, such as 360 mL of beer or 45 mL of 40% spirits or 150 mL of wine) or those who have frequently consumed alcohol (i.e. drinking more than 14 standard units of alcohol per week) within the 6 months prior to screening, or those who cannot abstain from alcohol during the trial period, or those who have a positive breathalyzer test; 11. Individuals who have taken any prescription or over-the-counter drugs, as well as any functional vitamins or herbal products within the 14 days prior to screening; 12. Those who have consumed excessive amounts of tea, coffee, or caffeinated beverages for a long time in the past (8 or more cups per day, 1 cup=250 mL); 13. It cannot be guaranteed that vigorous exercise, smoking, and special diets (including grapefruit, chocolate, tea, cola, or any caffeinated food or beverage, alcoholic beverage, or other food or beverage that affects drug absorption, distribution, metabolism, or excretion) will be prohibited from 48 hours before administration until the last blood collection; 14. Pregnant or lactating women, or female subjects who have had unprotected sex within two weeks prior to screening, or female subjects who have a positive blood pregnancy test; Female and male participants (or their partners) who have had fertility plans or donated sperm/eggs throughout the entire trial period and within 6 months after the end of the study, and who are unwilling to use one or more contraceptive measures during the trial period and within 6 months after the end of the study; 15. Those who cannot tolerate venipuncture or difficulty in venous blood collection; 16. Individuals with a history of fainting from needles or blood, or known severe bleeding tendencies; 17. Those who have special dietary requirements and cannot follow a uniform diet; 18. The researchers believe that there are any circumstances that may affect the provision of informed consent or adherence to the trial protocol by the subjects, or that the participation of the subjects in the trial may affect the trial results or their own safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 14 days after single injections | Adverse events,evaluate the safety of single injections of RAB001 at different doses |
| Serious adverse events | 14 days after single administration | serious adverse events during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter Cmax | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15 | PK parameter Cmax :Maximum peak plasma concentration (Cmax) |
| PK parameter AUC0-t | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter AUC0-t:Area under the concentration-time curve (AUC0-t) from time zero to time "t" . |
| PK parameter AUC0-∞ | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter AUC0-∞:AUC from time zero to infinity (AUC0-∞) . |
| PK parameter Tmax | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter Tmax.Time of Cmax (Tmax). |
| PK parameter T1/2z | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter T1/2z:Terminal-phase elimination half-life (t1/2) . |
| PK parameter-Vz/F | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter-Vz/F:Apparent Volume of Distribution During the Terminal Phase (Vz/F) of RAB001 in Plasma |
| PK parameter-CL | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter-CL:Systemic Clearance (CL) of RAB001 |
| PK parameter λz | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK parameter λz:Apparent Terminal Elimination Rate Constant (λZ) of |
| PK Parameter: CLss | The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15. | PK Parameter: CLss , the apparent systemic clearance from plasma observed during a dosing interval at steady state following extravascular administration |
| Bone turnover marker: BALP | Day 1、8 、15、29、43 、 57 | Change in Serum Bone Alkaline Phosphatase (BALP) Level |
| Bone turnover marker: PINP levels | Day 1、8 、15、29、43 、57 | PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels |
| Bone turnover marker: Osteocalcin (OC) Levels | Day 1、8 、15、29、43 、 57 | the bone turnover marker : Osteocalcin (OC) Levels |
| Bone turnover marker:CTX-I Levels | Day 1、8 、15、29、43 、57 | CTX-I (C-terminal Telopeptide of Type I Collagen )Levels the bone turnover marker |
| Bone turnover marker: VEGF | Day 1、8 、15、29、43、57 | Bone turnover marker: VEGF vascular endothelial growth factor |
Countries
China
Outcome results
None listed