NCT03319797已完成3 期
Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject Plus in the Treatment of Cartilage Defects of the Knee
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Tetec AG
- 入组人数
- 100
- 试验地点
- 20
- 主要终点
- Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).
研究概览
简要总结
Prospective, Multicenter, Single-arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of NOVOCART® Inject plus in the Treatment of Cartilage Defects of the Knee. The primary objective of this trial is to demonstrate efficacy of NOVOCART® Inject plus for the treatment of cartilage defects of the knee based on the Knee injury and Osteoarthritis Outcome Score (KOOS) responder rate 24 month after transplantation.
详细描述
The present study is a prospective, multicenter, single-arm phase III clinical trial to evaluate the efficacy and safety of NOVOCART® Inject plus in the treatment of patients with focal cartilage defects of the knee (medial or lateral femoral condyle or tibial plateau, trochlea or patella). The study will include adult patients between 18 and 65 years of age and pediatric patients (14 to 17 years) with closed epiphysis.
A total of 96 patients will be enrolled in the NOVOCART® Inject plus trial at about 20 clinical study sites in Europe. It is expected that each study site will enroll 3 to 9 patients.
The trial will consist of three phases (including screening, treatment and follow-up phase) with a maximum duration of 5 years and 4 months.
The treatment with NOVOCART® Inject plus requires 2 surgeries. During the first surgery autologous chondrocytes for transplant production will be harvested arthroscopically, then NOVOCART® Inject plus will be transplanted during a second surgery about 3 to 4 weeks later. In general, NOVOCART® Inject plus transplantation can be performed arthroscopically. However, depending on the defect localization, mini-arthrotomy may be indicated.
Eligibility will be assessed preoperatively at visit 1 (screening) and (up to a maximum of 3 months later) intraoperatively during the first arthroscopy (visit 2). During visit 2, cartilage biopsy samples will be taken from eligible patients and sent to TETEC AG for NOVOCART® Inject plus manufacturing. Transplantation will then be performed during a second arthroscopy 3 to 4 weeks later (visit 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is ≥ 18 and ≤ 65 years old at screening. Pediatric patients (14 to 17 years) with closed epiphysis may be included in selected countries. Closure of the distal femoral epiphysis of the target knee needs to be confirmed by MRI or x-ray.
- •Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
- •Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
- •If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different, knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
- •Patient has an intact, well contained chondral structure surrounding the defect (i.e. no diffusely thinned-out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
- •Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.
- •Patient has a stable knee joint or sufficiently reconstructed ligaments and no patella malalignment or a sufficiently corrected patella malalignment. Ligament repair is accepted, if performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation. Correction of patella malalignment must be performed before or during NOVOCART® Inject plus transplantation.
- •Patient has free range of motion (ROM) of the affected knee joint or ≤ 10° of active extension and flexion loss (compared to the other knee).
- •Patient has a baseline score of < 65/100 in the overall KOOS (KOOS5).
- •Only for female patients of childbearing potential (sexually mature, pre-menopausal and not surgically sterile): the patient is willing to use a medically accepted method of contraception until the day of NOVOCART® Inject plus transplantation.
- •Patient is willing and able to give written informed consent to participate in the study and to comply with all follow-up visits and assessments and the postoperative rehabilitation program.
- •Intraoperative inclusion criteria:
- •At visit 2, the following inclusion criteria from visit 1 need to be confirmed; all criteria must be answered with "yes" before the patient is considered eligible for the study:
- •Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy
- •Patients with focal articular cartilage defect(s) of the femoral condyle (medial or lateral), the trochlea, the patella or the tibial plateau (medial or lateral) of the knee.
- •Patient has one or two defects in the target knee with a defect-grade of III or IV according to the International Cartilage Repair Society (ICRS) classification or grade III or IV ICRS classification of osteochondritis dissecans lesions (ICRS-OCD).
- •If the patient has only one grade III or IV defect, the size of the defect is ≥ 4 and ≤ 12 cm2 post debridement. If the patient has two grade III or IV cartilage defects the total defect size is ≥ 4 and ≤ 12 cm2 post debridement. The defects must be located on different knee joint areas and both cartilage defects are to be treated with NOVOCART® Inject plus.
- •Patient has an intact intact, well-contained chondral structure surrounding the defect (i.e. no diffusely thinned out cartilage surface) and an articulating joint surface opposite to the defect(s) to be treated (≤ Grade I ICRS or ICRS-OCD classification).
- •Patient has intact menisci in the target knee; a maximum of 50% resection per meniscus is allowed. Completely healed meniscal transplants are accepted.
排除标准
- •Patient is unable to undergo magnetic resonance imaging (MRI).
- •Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas1 of the target knee.
- •Patient had a prior biologic reconstructive procedure (e.g. microfracture, mosaicplasty, chondrocyte transplantation) in the target knee at a location different from the defect location to be treated in the study. Prior biologic reconstructive procedures are accepted, if the previously treated defect is the same defect that is planned to be treated with NOVOCART® Inject plus (i.e. the prior method has failed) and these procedures were performed ≥ 24 months prior to screening visit
- •Patient had other prior surgical interventions interfering with the assessment of the NOVOCART® Inject plus treatment. Prior diagnostic arthroscopies with debridement and lavage are acceptable.
- •Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
- •Patient has degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade >
- •Patient has chronic inflammatory arthritis and/or infectious arthritis.
- •Patient has joint space narrowing > 1/3 in the target knee when compared to the other knee or < 3 mm joint space.
- •Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In suspected cases, the mechanical axis must be established radiographically by complete leg imaging in standing position and in anteriorposterior (a.p.) or rather posterioranterior (p.a.) projection. The Mikulicz line is not allowed to deviate more than 5 mm of the eminentia intercondylaris. If alignment is necessary, surgery has to be performed before, during or within 6 weeks after NOVOCART® Inject plus transplantation.
- •Patient has arthrofibrosis in the target knee.
- •Patient has diffuse chondromalacia (grade 1 'softening or swelling of cartilage' according to Outerbridge allowed).
- •Patient has metabolic arthropathies (e.g. gout, pseudo-gout)
- •Patient has bilateral lower limb pain or low back pain.
- •Patient has a known systemic connective tissue disease.
- •Patient has a current uncontrolled diabetes.
- •Patient has a known history of autoimmune disease.
- •Patient has a known history of immunological suppressive disorder or is taking immunosuppressants.
- •Patient is currently systemically or intra-articularly taking steroids and/or has used steroids within the last 30 days prior to screening visit
- •The patient has a history of Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS), Human T cell lymphotropic virus (HTLV), syphilis (Treponema pallidum) or active hepatitis B or C (HCV) infection with verified antigens. Patients with a cured hepatitis B or C infection and/or verified antibodies are not excluded.
- •The patient has a history of borreliosis.
- •The patient has an active systemic or local (at the site of surgery) infection, eczematization or inflammable skin alterations.
- •Patient has a known history of cancer within the past 5 years.
- •Patient has a known history of osteoporosis, uncontrolled primary hyperparathyroidism or hyperthyroidism, chronic renal failure or prior pathological fractures independent of the genesis.
- •Patient has any degenerative muscular or neurological condition that would interfere with evaluation of outcome measures including but not limited to Parkinson's disease, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).
- •Patient has a body mass index (BMI) > 35 kg/m
- •Patient is a woman who is pregnant or lactating.
- •Patient is currently participating, or has participated in any other clinical study within 3 months prior to screening visit
- •Patient has known current or recent history of illicit drug or alcohol abuse or dependence.
- •Patient has psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the patient's ability to comply with the study requirements, e.g., Alzheimer's disease.
- •Patient has a known intolerance to any constituents of NOVOCART® Inject plus.
- •Patient has comorbidities preventing the patient from undergoing surgery
- •Patient has any other condition, which, in the opinion of the investigator, would make the patient unsuitable for the study.
- •Intraoperative exclusion criteria:
- •At visit 2, the following exclusion criteria from visit 1 need to be confirmed; all criteria must be answered with "no" before the patient is considered eligible for the study:
- •Patient has grade II cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •Patient has more than 2 grade III or IV cartilage defects according to the ICRS or ICRS-OCD classification in the target knee.
- •The cartilage defects (ICRS or ICRS-OCD grade I or III or IV) affect more than 3 out of 6 joint areas2 of the target knee.
- •Patients with subchondral bone defects more than 2 mm deep (after resection of affected bone) unless adjuvant defect filling will be performed before or during NOVOCART® Inject plus transplantation.
- •Patient has arthrofibrosis in the target knee.
- •Patient has diffuse chondromalacia (grade 1 'softening or swelling of cartilage' according to Outerbridge allowed).
研究组 & 干预措施
Treatment with NOVOCART® Inject plus
Other
Treatment with NOVOCART® Inject plus (Autologous chondrocyte transplantation)
干预措施: NOVOCART® Inject plus (Drug)
结局指标
主要结局
Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5). The KOOS score ranges from 0 to 100 (100 indicating no symptoms and 0 indicating extreme symptoms).
时间窗: 24 month
Responder rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS5) defined as the average of the 5 subscale scores (ensuring identical weight from all subscales) at the 24 months follow-up assessment. The KOOS5 responder rate is defined as the proportion of patients with ≥ 10 points improvement in the KOOS5 from baseline to the 24 months visit.
次要结局
- Change in the KOOS5(24 month)
- Change in the 5 individual subscores of the KOOS(24 month)
- Patient satisfaction with treatment. Patients will be asked 4 questions (with 3 answer options each) related to their treatment satisfaction, no score provided.(24 month)
- Change in the grading according to the IKDC surgeons part(24 month)
- Morphological assessment of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score(24 month)
- Treatment-related adverse events (AEs)(24 month)
- Change in the International Knee Documentation Committee (IKDC) subjective score. The IKDC score ranges from 0 to 100, with 100 indicating the absence of symptoms and higher levels of functioning.(24 month)
- Change in EQ-5D-5L. The components are the EQ-5D-5L index ranging from <0 (worse than dead) to 1 (full health) and a visual analogue scale with the end points of 0 (worst health) and 100 (best health).(24 month)
- Change in activity level/ functional status. Patient questionnaire on activity (sporting habits) and functional status (degree of restriction in general), no score provided.(24 months)
- Biochemical MR assessment by T2 mapping(24 month)
- Time to treatment failure(24 month)
- Treatment failure rate(24 month)
研究者
研究点 (20)
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