A Multicenter, Randomized, Controlled, Blinded, Phase II Clinical Study to Evaluate the Efficacy, Safety, Tolerability, and PK/PD Profiles of RAB001 for Injection in Patients With Early-stage Non-traumatic Osteonecrosis Caused by Long-term Glucocorticoid Use.（LLP2A-Alendronate）
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 161
- 试验地点
- 1
- 主要终点
- Changes in Necrotic Area Volume of the Femoral Head (MRI)
研究概览
简要总结
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:
- . Change in femoral head necrotic lesion volume at 48 weeks (MRI)
- . Change in hip function score at 48 weeks (HHS, Harris Hip Score)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years ≤ age ≤ 69 years, gender not limited;
- •Patients with glucocorticoid-induced osteonecrosis of the femoral head (ONFH) according to the 2019 edition of the "Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults", with an ARCO stage of II, and confirmed by CT and MRI examinations to have no femoral head collapse, and the time from first glucocorticoid use to the screening period must exceed 30 days;
- •The participant has no plans for hip surgery on the target side within the next 54 weeks;
- •Participants with unilateral or bilateral ONFH are not restricted. For unilateral involvement, the affected side (as the target side) must have no femoral head collapse confirmed by hip CT examination. For bilateral involvement, hip CT examination must confirm that at least one side has no collapse (the non-collapsed side is the target side; if both sides are necrotic and neither has collapsed, the side with more severe necrosis is the target side. If the contralateral side of the target side meets the criteria for study-defined osteonecrosis, all study information must be recorded for that side as for the target side);
- •Participants must be informed about the study and voluntarily sign a written informed consent form before the trial.
排除标准
- •BMI ≥ 35 kg/m²;
- •The target-side osteonecrosis of the femoral head (ONFH) is classified as type M according to the China-Japan Friendship Hospital (CJFH) classification;
- •Inability to walk or to complete all the examinations, treatments, and follow-ups required by the trial protocol;
- •Currently receiving glucocorticoid pulse therapy;
- •Severe metabolic diseases, cardiovascular diseases, clinically significant atrial fibrillation, uncontrolled hypertension, uncontrolled asthma, symptomatic pulmonary fibrosis, recent gastrointestinal bleeding requiring transfusion, mental or psychological disorders;
- •History of deep vein thrombosis, with any invasive preventive/therapeutic measures taken within the last five years;
- •Current fracture or infection in either hip joint, or previous surgery on the target-side hip joint;
- •Planned oral surgery within 54 weeks after enrollment;
- •Known hereditary bone diseases, such as achondroplasia, osteogenesis imperfecta, hypophosphatemic rickets, etc.;
- •Use of medications for bone metabolic diseases, integrins, α4β1 inhibitors/antagonists, or anti-VEGF drugs within 6 months or 5 half-lives (whichever is longer) prior to screening, as detailed in section 12.7;
- •Participants who have received opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), or other pain medications within 5 half-lives prior to screening;
- •Comorbidities that, in the investigator's judgment, may affect the clinical efficacy assessment of the hip joint, such as knee osteoarthritis, scoliosis, pelvic or lower limb deformities, etc.;
- •Previous allergy or contraindication to alendronate;
- •Any of the following abnormal laboratory findings during screening:
- •Phosphate level < LLN; Patients with decompensated liver function (e.g., complications of portal hypertension such as ascites, gastroesophageal variceal bleeding, sepsis, hepatic encephalopathy, hepatorenal syndrome, etc.); Estimated glomerular filtration rate (eGFR) < 35 mL/min/1.73 m² (calculated based on creatinine using the CKD-EPI Creatinine 2009 Equation); Hemoglobin < 100 g/L; Prolonged QT interval (male > 450 msec, female > 470 msec).
- •Donation or loss of blood/plasma > 400 mL within 3 months prior to screening (except for physiological blood loss in females);
- •History of drug abuse within 2 years prior to screening;
- •History of substance abuse within 2 years prior to screening;
- •Pregnant or breastfeeding women, or female participants who have had unprotected sexual intercourse within 6 weeks prior to screening, or female participants with a positive blood pregnancy test; participants (or their partners) planning to conceive or donate sperm/eggs during the trial and for 6 months after study completion, or unwilling to use one or more contraceptive methods during the trial and for 6 months after study completion;
- •Participation in other drug clinical trials with medication use within 3 months prior to screening;
- •Participants deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
High-dose
Intravenous infusion RAB001 1200μg/kg
干预措施: RAB001 high dose (Drug)
Medium-dose
Intravenous infusion RAB001 750μg/kg
干预措施: RAB001 medium dose (Drug)
Low-dose
Intravenous infusion RAB001 400μg/kg
干预措施: RAB001 low dose (Drug)
Alendronate
干预措施: Alendronate (Fosamax) (Drug)
结局指标
主要结局
Changes in Necrotic Area Volume of the Femoral Head (MRI)
时间窗: week48
Changes in Hip Function Scores (HHS)
时间窗: week48
It is a clinical tool widely used to assess hip function and pain levels. The scoring system is administered by physicians through questionnaires and physical examinations, covering multiple dimensions such as pain, function, deformity, and range of motion.Higher scores indicate milder symptoms in patients, with a maximum of 100 points and a minimum of 0 points.
次要结局
- Rate of non-collapse of the femoral head(defined as femoral head collapse ≤ 2mm based on hip CT + MRI examination)(week24 and week48)
- Changes in the volume of the femoral head necrotic area (MRI)(week24)
- Changes in Hip Function Scores (HHS)(week24)
- Changes in bone mineral density (DEXA) of the proximal femur (total hip) and lumbar spine (L1-L4)(week24and week48)
- Time to progression of osteonecrosis in the target-side femoral head compared to baseline (defined as femoral head collapse > 2mm based on hip CT + MRI examination)(week48)
- Changes in WOMAC scores(week24 and week48)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(week 48)
- Incidence of anti-drug antibodies (ADA)(week1、week7、week25、week49 week53)