A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Trial to Investigate the Efficacy and Safety of Weekly Intra-articular (i.a.) Injections of 10, 30, and 100 µg of AS902330 for Three Consecutive Weeks in Patients With Acute Cartilage Injury of the Knee
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Cartilage Defect Volume at Month 12
研究概览
简要总结
Several people all over the world suffer from cartilage injuries in the knee. Symptoms include pain, joint swelling, and loss of function. Without repair, cartilage injury may ultimately lead to osteoarthritis (OA). Natural healing is poor, and to date treatment is available only for deep cartilage defects involving also the underlying bone. A promising candidate for drug treatment of cartilage injury is sprifermin (AS902330), a recombinant form of the human fibroblast growth factor (FGF) 18.
So far, the drug has been used in subjects with different stages of knee OA in two ongoing studies without emerging safety issues following single and multiple intra-articular injections of ascending doses. However, OA represents late-stage cartilage injury, where repair might be difficult due to diffuse damage, reduced responsiveness of the cartilage, and/or the involvement of other joint structures.
This clinical trial is meant to provide the proof of concept and to identify an efficacious dose of sprifermin (AS902330) for the treatment of adult subjects with acute cartilage injuries of the knee. The first subject for this trial was treated on the 19th of April 2010.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute cartilage lesion of ICRS grade 2 to 4 at the femoral condyle of the knee (= target knee)
- •Age: 18 to 45 years
- •Sex: male or female. Women of childbearing potential (that is, all female subjects after puberty unless they are post-menopausal for at least 2 years or surgically sterile) must have negative serum and urine pregnancy tests at screening and Visit 1, respectively, and must use a highly effective method of contraception.
- •History of pain and effusion of the target knee post-injury
- •Injury within 4 to 12 weeks prior to 1st treatment with investigational medicinal product (IMP)
- •Written informed consent prior to any trial-related activity
排除标准
- •Personal medical history of osteoarthritis OA in either knee
- •Any previous surgery on the target knee
- •History of swelling of the target knee along with pain on weight-bearing, or arthroscopy for diagnostic purposes during the 12 months preceding injury
- •Corticosteroid (intra-articular) injection into the target knee during the preceding 12 months
- •Any other intra-articular injection into the target knee during the preceding 3 months
- •Any concurrent injury (for example, arthrolith, anterior cruciate ligament rupture, meniscus tear) of the target knee requiring surgical intervention
- •OA or any pre-existing cartilage damage in the target knee, as revealed by MRI
- •Legal incapacity or limited legal capacity
- •Subjects who are imprisoned or institutionalized by regulatory or court order
- •Pregnancy or lactation
- •Participation in another clinical trial within the past 30 days
- •Any condition or findings in the medical history or in the pre-trial assessments that in the opinion of the Investigator constitutes a risk or contraindication for participation in the trial or that could interfere with the trial objectives, conduct or evaluation
- •Known hypersensitivity to the trial treatment or diluents
- •Significant renal or hepatic impairment, as indicated by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) greater than (>) 3 times the upper limit of normal (ULN); total bilirubin >1.5 times ULN (except in case of Gilbert's syndrome); creatinine >1.5 times ULN; hemoglobin less than (<5.5) millimole per liter (mmol/L), white blood cell count (WBC) <2.5 * 10^9 per liter, or platelets <75 *10^9 per liter)
- •Any suspicion of intra-articular infection
- •Any known active infections that may compromise the immune system such as human immunodeficiency virus (HIV), Hepatitis B or C infection
- •History of sarcoma and/or of other active malignancy within five years, except adequately treated basal cell or squamous cell carcinoma of the skin
- •Open growth plate, as revealed by MRI
- •Diagnostic arthroscopy after injury and within 4 weeks prior to treatment start
研究组 & 干预措施
Sprifermin (AS902330) 10 mcg
干预措施: Sprifermin (AS902330) 10 mcg (Drug)
Sprifermin (AS902330) 30 mcg
干预措施: Sprifermin (AS902330) 30 mcg (Drug)
Sprifermin (AS902330) 100 mcg
干预措施: Sprifermin (AS902330) 100 mcg (Drug)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change From Baseline in Cartilage Defect Volume at Month 12
时间窗: Baseline, Month 12
Percent change in cartilage defect volume was calculated based on central magnetic resonance imaging (MRI): (volume at Month 12 minus volume at baseline)\*100/volume at baseline.
次要结局
- Percent Change From Baseline in Cartilage Defect Volume and Cartilage Defect Thickness in the Target Knee at Months 3 and 6(Baseline, Months 3 and 6)
- Change From Baseline in Cartilage Defect Volume in the Target Knee at Months 3, 6 and 12(Baseline, Months 3, 6 and 12)
- Change From Baseline in Cartilage Defect Thickness in the Target Knee at Months 3, 6 and 12(Baseline, Months 3, 6 and 12)
- Number of Participants With Response to Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Sub-scales(Months 3 (M3), 6 (M6) and 12 (M12))
- Change From Baseline in Boston Leeds Osteoarthritis Knee Score (BLOKS) Sub-scale (Bone Marrow Lesion [BML] Size, Osteophyte Size, Meniscal Extrusion Score [MES], and Meniscal Tear Score [MTS]) Scores at Month 12(Baseline, Month 12)
- Number of Participants With Shift From Baseline in BLOKS Sub-Scales (Cartilage 1, Synovitis, Effusion) Scores at Month 12(Month 12)
- Number of Participants With Change From Baseline in International Cartilage Repair Society (ICRS) Grade at Months 6 and 12(Baseline, Months 6 and 12)
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scale Scores and International Knee Documentation Committee (IKDC) Score at Months 3, 6 and 12(Baseline, Months 3, 6 and 12)
- Number of Participants With Global Evaluation of Treatment Benefit(Months 3, 6 and 12)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Local TEAEs, Systemic TEAEs, TEAEs Leading to Discontinuation and Serious Adverse Events (SAEs)(Baseline up to Month 12)
- Number of Participants With Acute Inflammatory Reactions(Baseline up to Month 12)
- Number of Participants With Binding Antibodies (BAbs) and Neutralizing Antibodies (NAbs) to Fibroblast Growth Factor 18 (FGF18)(Week 1 (pre-dose), Week 2 (pre-dose), Week 4, Months 3 and 12)