A Phase 2/3 Prospective, Multicentre Randomized, Double-blind Trial, Comparing Intra-discal Allogeneic Adult BM-MSC Therapy and Sham-treated Controls in Subjects With Chronic LBP Due to Lumbar DDD Unresponsive to Conventional Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 113
- 试验地点
- 9
- 主要终点
- Change from Baseline Pain Clinical response at 12 months
研究概览
简要总结
This will be a multicenter, prospective, double blind, randomized phase 2/3 trial comparing culture-expanded allogeneic adult BM-MSCs with sham-treated controls.
This trial will evaluate the efficacy of intradiscal injection of BM-MSCs in chronic low back pain due to lumbar degenerative disc disease (DDD) unresponsive to conventional therapy .
Visual analog scale (VAS) and functional status (by Oswestry Disability Index - ODI) will be evaluated 12 months after treatment, defining responders in case of improvement of VAS for pain of at least 20% and 20 mm between baseline and month 12, or improvement of ODI of 20% between baseline and month 12.
详细描述
Degenerative disc disease (DDD) presents a large, unmet medical need. One of the most important public health problems, it affects 70 million Europeans, accounts for 42% of patients with chronic low back pain and costs over $100 billion each year in the European Union. DDD results in a disabling loss of mechanical function. Today, no efficient therapy is available. The disease results from degeneration of cartilage discs with loss of the collagen matrix and nucleus pulposus chondrocyte. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 1 and 2 trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement of cartilage signal. To develop the world's first effective treatment of DDD, RESPINE aims to assess, via a randomized, controlled, phase 3 clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly (within 3 months) and durably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 60 years.
- •Symptomatic chronic low back pain unresponsive to conservative therapy (including physical therapy performed during at least 1 month before inclusion and pain medication with level 2 analgesics in failure or intolerant to level during at least 1 month) for at least 3 months.
- •DDD assessed by (Pfirrmann's score modified Griffith et al) grade 4 to 7 at one level. If second level, it should be adjacent (Pfirrmann's score 1-4 maximum)
- •Low back Pain baseline > 40 mm on VAS (0-100).
- •NSAID washout of at least 2 days before screening
- •Painkillers washout of at least 24 hours before screening
排除标准
- •Congenital or acquired diseases leading to spine deformations that may upset cell application (hyperlordosis, scoliosis, isthmus lesion, sacralization and hemisacralization).
- •Symptomatic posterior lumbo-articular osteoarthritis or predominant facet syndrome on Xray or MRI (osteophyte and facet hypertrophy).
- •Prior to the screening visit, has received:
- •Oral corticosteroid therapy within the previous 3 months, OR
- •Intramuscular, intravenous or epidural corticosteroid therapy within the previous 3 months
- •Spinal segmental instability (defined by lumbar dynamic X-Ray in extension/flexion with antero-post translation > 3 mm and/or angular mobility > 15°).
- •Spinal canal stenosis (Schizas score > B).
- •History of spinal infection.
- •Lumbar disc herniation with non truncated sciatica or cruralgia, as well as lumbar cysts and radiculopathy
- •Previous discal puncture or previous spine surgery.
- •DDD on 3 levels, or DDD on 2 levels but not adjacent, or DDD with modic 2 or 3 phases
- •Patients not eligible to the intravertebral disc surgery
- •Patients who have the risk to undergo a surgery in the next 6 months
- •Obesity with body mass index (BMI in Kg/size in m2) greater than 35 (obesity grade II).
- •Participation in another clinical trial or treatment with another investigational product within 30 days prior to inclusion in the study.
- •Abnormal blood tests: hepatic (alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 × upper limit of normal (ULN)), renal, pancreatic or biliary disease, blood coagulation disorders, anemia or platelet count of <100 × 109/
- •Significant medical problems, such as uncontrolled hypertension, symptomatic heart failure; or any other clinically relevant condition or current medication that in the opinion of the investigator contra-indicates the use of any of the study or rescue medications.
研究组 & 干预措施
Allogenic BM-MSCs Injection
Injection of a dose of 20.106 allogenic BM-MSCs via imaging control into the disk affected by DDD where they are expected to exert their therapeutic effects.
干预措施: Allogenic BM-MSCs Injection (Drug)
Sham Procedure
anesthetic infiltration with 2 ml of 1% xylocaine in the paravertebral muscles close to the affected segment
干预措施: Sham Procedure (Other)
结局指标
主要结局
Change from Baseline Pain Clinical response at 12 months
时间窗: baseline to month 12
The clinical response is defined as the Pain relief measure with Visual Analogue Scale (VAS) of at least 20 mm decrease on VAS scale between baseline and month 12.
Change from Baseline Oswestry Disability Index (ODI) measure at 12 months
时间窗: baseline to month 12
at least 20% improvement of functional index ODI at month 12 compared to baseline.
次要结局
- Measure disability and quality of life evolution of the patient(Baseline, 3,6,12 and 24 months)
- Disability and quality of life evolution(baseline, 3,6,12 and 24 months)
- Pain killers(baseline, 1, 3,6,12 and 24 months)
- Measure of the Chronic low back pain(baseline, 1, 3,6,12 and 24 months)
- Employment and work status(baseline, 1, 3,6,12 and 24 months)
- reporting of Serious Adverse Events (SAE)(baseline, 1, 3,6,12 and 24 months)
- Structural assessment(baseline, 1, 3,6,12 and 24 months)
- Evaluation of cost(24 months)
- Immune response / Analytical control(baseline, 1, and 6 months)