Safety, Tolerability, and Preliminary Efficacy of Intra-Articular Injection of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Non-Traumatic Avascular Necrosis of the Femoral Head: A Single-Arm, Open-Label, Dose-Escalation Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 15
- 主要终点
- Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a first-in-human, single-arm, open-label, dose-escalation, exploratory Phase I clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of local injection of mesenchymal stem cell-derived exosomes for non-traumatic osteonecrosis of the femoral head (ONFH).
A total of 15 treatment-naïve patients with non-traumatic, non-septic ONFH at ARCO stages I-IIIA, treated at the outpatient clinic of our hospital between June 2026 and June 2027, will be enrolled. Under ultrasound guidance, exosomes will be administered via an anterior approach through a single intra-articular injection into the hip joint. Three dose cohorts will be evaluated: \(4 \times 10^{10}\), \(1.2 \times 10^{11}\), and \(3.6 \times 10^{11}\) particles per administration per hip. The low-dose cohort will include 3 patients, while the medium- and high-dose cohorts will each include 6 patients. The dose-limiting toxicity observation period will extend from the first administration to 14 days after the final administration.
Exosomes will be administered once every 2 weeks at a volume of 3 mL per injection. Three administrations will constitute one treatment course, with a total treatment duration of 4 weeks. The primary endpoints are safety outcomes, including the incidence of adverse events, serious adverse events, and dose-limiting toxicities after administration. Secondary exploratory efficacy endpoints include changes in the Visual Analog Scale (VAS) pain score, Harris Hip Score (HHS), and radiological findings of the femoral head. The follow-up period will be 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70 years, inclusive, with no restriction on sex.
- •A diagnosis of non-traumatic osteonecrosis of the femoral head (ONFH) confirmed by clinical manifestations and imaging findings, with ARCO stage II or IIIA disease. Patients with advanced femoral head collapse (ARCO stage IIIB or IV) will be excluded.
- •The target hip must be treatment-naïve, defined as no prior hip-specific interventional or injection-based treatment for the affected side.
- •Ability to understand and voluntarily provide written informed consent, with an expectation of completing long-term follow-up.
排除标准
- •Presence of an active infection in the target joint (e.g., septic arthritis or infectious osteomyelitis), or skin disruption, infection, or other abnormalities at the intended injection site.
- •Receipt of intra-articular injection therapy in the affected hip within 3 months before screening, including corticosteroids or sodium hyaluronate.
- •Presence of any active systemic autoimmune disease (e.g., rheumatoid arthritis or systemic lupus erythematosus) or a primary or secondary immunodeficiency disorder.
- •History of malignancy.
- •Clinically significant abnormal laboratory findings during screening, including impaired hepatic or renal function (ALT or AST >1.5 × the upper limit of normal [ULN], or serum creatinine >ULN), or clinically significant abnormalities on complete blood count.
- •Coagulation disorders (PT or APTT >1.5 × ULN), active bleeding risk, or a requirement for long-term anticoagulant therapy that cannot be interrupted.
- •Severe systemic chronic disease not adequately controlled with medication, such as severe heart failure or uncontrolled severe hypertension or diabetes mellitus.
- •Severe alcohol dependence or a history of substance or corticosteroid abuse that, in the investigator's judgment, cannot be controlled during the trial and may substantially compromise treatment adherence or efficacy assessment.
- •Participation in another clinical trial within 3 months before screening, or previous treatment with stem cells, exosomes, or other cell- or biologic-based therapies.
- •Known hypersensitivity to any component of the investigational product.
- •Women who are pregnant or breastfeeding, or patients who plan to conceive during the trial or within 6 months after the last administration.
研究组 & 干预措施
Low-dose cohort
干预措施: Exosome Intervention Group (Biological)
Middle-dose cohort
干预措施: Exosome Intervention Group (Biological)
High-dose cohort
干预措施: Exosome Intervention Group (Biological)
结局指标
主要结局
Number of participants with dose-limiting toxicities (DLTs)
时间窗: Day 1 through Day 43
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), graded by CTCAE v6.0
时间窗: Day 1 through Month 12
Number of participants with suspected unexpected serious adverse reactions (SUSARs)
时间窗: Day 1 through Month 12
次要结局
- Change from baseline in necrotic lesion volume of the femoral head on MRI(Baseline, Month 6, 12)
- Change from baseline in bone marrow edema area of the femoral head on MRI(Baseline, Month 6, 12)
- Number of participants with stable or improved ARCO stage(Baseline, Month 6, 12)
- Number of participants with successful intra-articular injection(Day 1, 15, 29)
- Number of participants with local reactions after injection(Day 1, 15, 29)
- Change from baseline in Visual Analogue Scale (VAS) pain score(Baseline, Month 3, 6, 12)
- Change from baseline in Harris Hip Score(Baseline, Month 3, 6, 12)
- Change from baseline in WOMAC score(Baseline, Month 3, 6, 12)
研究者
Deng XiaoLi
Doctor
Beijing Jishuitan Hospital