Treatment of Patellofemoral Osteoarthritis With Nasal Chondrocyte-based Engineered Cartilage Implantation in a Randomized, Controlled, Multi-center Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 75
- 试验地点
- 9
- 主要终点
- Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain
研究概览
简要总结
The purpose of this investigator-initiated study is to assess the efficacy of treating patellofemoral osteoarthritis with an Advanced Therapy Medicinal Product (ATMP), autologous nasal chondrocyte tissue engineered cartilage (N-TEC), in comparison with a standard therapy using platelet rich plasma injections.
The engineered cartilage graft is obtained by culturing expanded autologous nasal chondrocytes within a collagen type I/III membrane.
详细描述
Knee osteoarthritis (OA) is one of the most common causes for pain and disability with over 260 million people affected worldwide. Recent studies found that knee OA often starts in the patello-femoral compartment of the knee (PFOA) and is diagnosed in ~39% of people with knee pain aged above 30 years. Thus, PFOA and progression to full OA plays a crucial role in the reduction of quality of life of many people and in the raise of healthcare costs.
The goal of this phase II trial is to (i) evaluate the efficacy of autologous Nasal Chondrocytes Tissue Engineered Cartilage (N-TEC) in comparison to an active comparator (Platelet Rich Plasma (PRP) injections) based on patients' self-assessed outcome scores (Knee Osteoarthritis Outcome Score (KOOS Pain), and to (ii) verify tissue regeneration as the postulated mode of action and thus the disease-modifying properties of the graft, as previously indicated in animal studies (x-ray, MRI). This proposed phase II trial will evaluate whether N-TEC improves the clinical efficacy, leading to an increase of at least 15 points higher in the main primary outcome (KOOS (pain) change at 24 months) than the comparator group. Secondary endpoints will include amongst others KOOS subscales (symptoms, pain, activity of daily living (ADL), sports, Quality of Life (QOL)), Kujala Anterior Knee Pain Scale, Western Ontario and McMaster Universities Osteoarthritis score (WOMAC), Marx Activity Rating Scale (MARS) and EQ-5d assessment at 6, 12 and 24 months compared to baseline and between groups. Further secondary endpoints will be the number of subjects non-responding to treatment (i.e., improvement in KOOS Pain below 13 units on a scale of 0-100) and treatment failures (deterioration of more than 13 points compared to baseline or switching to other regenerative treatments or joint replacement to evaluate efficacy). Adverse events will be recorded during the full course of the trial to assess safety. This will require enrolling a total of 75 patients in a multicenter, prospective study involving 9 clinical centers.
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
- 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
- •Patient age is ≥18 and ≤ 65 years at time of screening.
- •Symptomatic PFOA grade 1-3 according to Iwano Classification
- •Chondropathy Grade 3-4 according to ICRS classification of the patella, trochlea femoris or both
- •Baseline score of <60 on the KOOS Pain subjective knee evaluation.
- •Free range of motion of the affected knee joint or ≤ 5° of extension loss and minimum 125° flexion.
- •Patient is willing and able to give written informed consent to participate in the study and to comply with all study requirements, including attending all follow-up visits and assessments and to complete postoperative rehabilitation regimen.
- •Minimum values for women: Haemoglobin 110g/l, Platelets 150G/l, INR<1.3
- •Minimum values for men: Haemoglobin 120g/l, Platelets 150G/l, INR<1.3
- •Non-surgical standard of care options except for PRP have been exhausted.
排除标准
- •Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol or in a dependency or employment with the sponsor.
- •Patient is unable to understand the patient information
- •Patient is unable to undergo magnetic resonance imaging (MRI)
- •Prior surgical treatment of the target knee within 12 months (Note: prior diagnostic arthroscopy with debridement and lavage are acceptable within 12 months).
- •Radiologically apparent degenerative joint disease of the tibiofemoral joint as determined by X-ray (Kellgren and Lawrence grade > 2) or MRI or pain in the tibiofemoral joint as assessed by clinical examination
- •Patient has excessive varus or valgus deformity (>5°)
- •Patient had a patellar dislocation in the afflicted knee in the last 2 years.
- •Patient has a symptomatic meniscus lesion (or removal exceeding ½), as indicated by clinical examination (joint line tenderness and McMurray test positive) and MRI.
- •Patient has a body mass index (BMI) >35 kg/m
- •Patient has chronic rheumatoid arthritis, and/or infectious arthritis
- •Any concomitant painful or disabling disease of the spine, hips, or lower limbs that would interfere with evaluation of the afflicted knee.
- •Patient has a known immunological suppressive disorder or is taking immunosuppressives.
- •Patient had any intra-articular injections into the affected knee within the last 3 months before baseline visit
- •Instability of anterior, posterior collateral ligaments
- •The patient has a HIV/AIDS infection. (regulatory requirement)
- •The patient has an acute Treponema pallidum (syphilis) infection. (regulatory requirement)
- •The patient has an active hepatitis B or C infection assessed according to local laboratory standards using an antibody test and if positive, confirmatory test for active infection. Patients with a cured hepatitis B or C infection are not excluded. (regulatory requirement)
- •Patient is pregnant, breast feeding or anticipates becoming pregnant within 24 months after surgery.
- •Patient is currently participating or has participated in any other clinical study within 3 months prior to the screening visit.
- •Patient has known current or recent history of illicit drug or alcohol abuse or dependence defined as the continued use of alcohol or drugs despite the development of social, legal or health problems.
- •Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study.
- •Any known allergies, especially for porcine collagen, penicillin or streptomycin (manufacturing)
- •patients with increased anesthesiological and surgical risks (e.g. known or predicted difficult airway, myocardial infarction <60 days prior to surgery)
- •patients with increased bleeding risk (e.g. coagulopathies)
- •patients on anticoagulants whose anticoagulant therapy cannot be interrupted as appropriate to the given agent(s) and underlying condition
- •Patients with any active infections
研究组 & 干预措施
Platelet Rich Plasma
Total of 3 injections of about 5 ml each of platelet rich plasma (PRP), autologous Conditioned Plasma ACP®, Arthrex, one injection per week for three consecutive weeks.
干预措施: Platelet rich plasma (Biological)
N-TEC
N-TEC is based on autologous nasal chondrocytes expanded and further cultured on type I/III collagen membranes for 2 weeks to allow cells to produce extracellular matrix containing cartilage specific proteins. The IMP is implanted in the knee at the patellofemoral joint.
干预措施: N-TEC (Biological)
结局指标
主要结局
Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain
时间窗: 24 months
mean change in Knee Injury and Osteoarthritis Outcome Score for pain from baseline to 24 months between groups Minimum score: 0 Maximum score :100 (higher score means no knee problems)
次要结局
- Biovigilance(until 24 months)
- Kellgren Lawrence classification(until 24 months)
- Knee Injury and Osteoarthritis Outcome questionnaire(until 24 months)
- Iwano classification(until 24 months)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score(until 24 months)
- MOCART score(until 24 months)
- Kujala self reported questionnaire(until 24 months)
- Visual Analogue Scale(Unitl 24 months)
- Global Rating Of Change (GROC) likert scale(until 24 months)
- Marx Activity Rating Scale (MARS) score(until 24 months)
- Number of non responders(Until 24 months)
- Number of treatment failures(Until 24 months)
- MRI Osteoarthritis Knee Score (MOAKS)(Until 24 months)
- EQ5d questionnaire(until 24 months)
- Knee Injury and Osteoarthritis Outcome questionnaire(until 24 months)
- Iwano classification(until 24 months)
- Kellgren Lawrence classification(until 24 months)
- MOCART score(until 24 months)
- Kujala self reported questionnaire(until 24 months)
- EQ5d questionnaire(until 24 months)
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score(until 24 months)