Zhongshan Lebo Ruichen Biopharmaceutical Co Ltd.

This is a multicenter, randomized (similar to drawing lots, where the treatment you receive is not chosen by you or the researchers), controlled, blinded (the three dose groups of the investigational drug are blinded, meaning neither you nor the blinded researchers will know which dose you are receiving) clinical study to evaluate the efficacy, safety, and PK/PD profiles of RAB001 for injection in patients with early-stage non-traumatic osteonecrosis caused by long-term glucocorticoid use.
A parallel-group enrollment design will be used, with a total of approximately 160 subjects expected to be enrolled (High-dose A: 1200 μg/kg；Medium-dose B: 750 μg/kg ；Low-dose C: 400 μg/kg): Control group (D: Alendronate Sodium Tablets (Fosamax) 70 mg orally once weekly) = 40 cases . If you agree to participate in this trial, you will have a 25% chance of being assigned to one of the groups mentioned above.
Supportive treatment: Calcium (recommended dose: 1000-1200 mg/d) + Vitamin D (recommended dose: 600-800 IU/d). The study physician may choose the appropriate dosage of calcium and vitamin D based on the subject's specific conditions.
Primary endpoints:
1. . Change in femoral head necrotic lesion volume at 48 weeks (MRI)
2. . Change in hip function score at 48 weeks (HHS, Harris Hip Score)

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.

主要目的： 评估膝骨关节炎参与者关节腔内注射 RAB001 的安全性和耐受性。 次要目的： (1) 评估膝骨关节炎参与者关节腔内注射 RAB001 的药代动力学特征。 (2) 评估注射用 RAB001 关节腔内注射给药治疗膝骨关节炎的初步有效性。