A Phase II Trial of RAB001 (LLP2A-Alendronate) for Steroid-Induced Early-Stage Osteonecrosis of the Femoral Head

Exclusion Criteria

• •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.