A Prospective, Randomized and Non-randomized, Controlled, Single-blind and Open-label, Dose-finding, Multi-center, Parallel Group Study of Safety/Efficacy of KUR-113 Bone Graft Versus Local Autograft for the Treatment of Single-level Transforaminal Lumbar Interbody Fusion
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 15
- 主要终点
- Radiographic interbody fusion
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of KUR-113 Bone Graft (TGplPTH1-34 in fibrin) compared to local autograft for the treatment of Degenerative Disk Disease (DDD).
详细描述
Degenerative disc disease (DDD) is a common disorder of the lumbar spine. Clinically, DDD causes discogenic back pain and may cause related radicular, neuropathic, claudicatory, and referred pain.
This is a prospective, randomized and non-randomized, controlled, single-blind and open-label, dose-finding, multi-center study which intends to demonstrate the safety and efficacy of KUR-113 Bone Graft (TGplPTH1-34 in fibrin) versus local autograft. The study will enroll 50 patients with Degenerative Disk Disease (DDD) requiring single-level interbody fusion along with posterolateral fusion (PLF) with posterior fixation who meet eligibility criteria and agree to participate in the study. Safety and efficacy of KUR-113 Bone Graft will be evaluated by analyzing all clinical as well as radiological endpoints and adverse events. This phase 2a study is not powered to detect non-inferiority. All patients will undergo clinical and radiological assessments at initial hospital discharge (on average 3 days post-surgery), 6 weeks, 3, 6, 12 and 24 months.
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
- Single (Participant)
盲法说明
Due to the different technical procedures between the control and the intervention arms (KUR-113 Bone Graft versus local autograft), investigators cannot be blinded to the treatment. However, all stage 1 patients will remain blinded for the duration of their participation in the study. All stage 2 patients will receive the same treatment and will be unblinded.
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent by the patient.
- •Male or female patient ≥ 25 up to and including 75 years old. Females of childbearing potential with a negative urine pregnancy test at Screening. Females of childbearing potential must agree to use acceptable contraception for at least 12 months after surgery and investigational product placement.
- •Patients with degenerative disc disease with up to grade 1 spondylolisthesis and with leg pain requiring up to 3 levels of laminectomy/decompression and a single-level fusion (L2 - S1). DDD is defined by the presence of one or more of the following:
- •instability (angulation ≥ 5 degrees or translation ≥ 3 mm on flexion/extension radiographs),
- •osteophyte formation of facet joints or vertebral endplates,
- •decreased disc height by > 2 mm, but dependent upon the spinal level,
- •scarring/thickening of ligamentum flavum, annulus fibrosis or facet joint capsule,
- •disc degeneration and/or herniation,
- •facet degeneration,
- •vacuum phenomenon.
- •Patients with an Oswestry Disability Index (ODI) score ≥
- •Patients with a Visual Analogue Scale (VAS) leg score ≥
- •Failed conservative treatment (physical therapy, bed rest, medications, spinal injections or transcutaneous electrical nerve stimulation) for a period of 6 months prior to study enrollment.
- •Patients willing to undergo PK sampling.
排除标准
- •Patients with open epiphyseal plates.
- •Patient requiring emergency spinal decompression or spinal fusion.
- •Patients requiring multilevel fusion or expected to need secondary intervention within one year following surgery.
- •Any prior fusion or attempted fusion at an adjacent level.
- •Any prior fusion or attempted fusion at the index level.
- •Pregnant or breast-feeding women.
- •Known or suspected allergies to any of the components of KUR-113 Bone Graft (e.g.
- •hypersensitivity to aprotinin).
- •Any prior use of teriparatide or abaloparatide or graft material containing PTH1-
- •Patients with hypercalcemic disorders (e.g., primary hyperparathyroidism).
- •Patients with Paget's Disease or unexplained high levels of alkaline phosphatase.
- •Prior radiation therapy involving bone.
- •Medical history or radiographic evidence of a metabolic bone disorder (e.g. Paget's Disease) or other condition that would negatively impact the healing process.
- •Any medical condition requiring radiotherapy or immunosuppression.
- •History of thyroid autoimmune disease (Hashimoto's thyroiditis, Graves' disease) or hyperthyroidism.
- •Patients on chronic systemic steroids (i.e. > 14 consecutive days) within 6 months prior to Screening Visit.
- •Osteopenia (T score < -1.0) or osteoporosis of the spine (T score < -2.5).
- •DDD related to benign or malignant tumor.
- •History or presence of active malignancy.
- •Hereditary disorders predisposing to osteosarcoma.
- •Patients with invasive skin cancer.
- •Evidence of local or systemic infection.
- •Patients with known active COVID-19 disease.
- •Current smokers.
- •Type 1 diabetes (regardless of HbA1c) or Type 2 diabetes with a documented HbA1c > 7.
- •Any acute or chronic concurrent medical conditions that in the Investigator's opinion are a contraindication to the procedure and study participation.
- •Participation in another investigational study within 30 days prior to surgery for investigational devices, or within the last three months for investigational drugs. (Note: trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials).
- •Known substance abuse, psychiatric disorder or a condition which, in the opinion of the investigator, may influence the healing or ability to comply with protocol requirements.
- •Involved in active litigation relating to his/her spinal condition or workers compensation claimants.
- •BMI greater than 40.
研究组 & 干预措施
KUR-113, Stage 1
During stage 1, subjects randomized to this arm will receive TGplPTH1-34 in fibrin (0.4mg/ml) that will be applied within and around a polyetheretherketone (PEEK) intervertebral cage. The maximum dose that will be applied is 4 mg of TGplPTH1-34 in 10mL KUR-113 Bone Graft.
干预措施: TGplPTH1-34 in fibrin (Combination Product)
Autologous Bone Graft
During stage 1 of the study, subjects randomized to this arm will receive local autologous bone graft. In the event of insufficient local autograft, Iliac crest bone graft may be used to supplement.
干预措施: Autologous Bone Graft (Other)
KUR-113, Stage 2
During stage 2, subjects will receive TGplPTH1-34 in fibrin that will be applied within and around a PEEK intervertebral cage at a concentration of 0.7mg/ml. The concentration received was selected by the DSMB based on the results of stage 1. The maximum dose that will be applied is 7 mg of TGplPTH1-34 in 10mL KUR-113 Bone Graft.
干预措施: TGplPTH1-34 in fibrin (Combination Product)
结局指标
主要结局
Radiographic interbody fusion
时间窗: Month 12 post-surgery
Evidence of bridging trabeculae or continuous bony connection between superior and inferior vertebral body on CT-scan as determined by an independent radiology expert panel (IREP).
次要结局
- Back Pain(Initial discharge from hospital (on average 3 days post-surgery), Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery)
- Composite Endpoint(Month 6 and Month 12 post-surgery)
- Radiographic posterolateral fusion(Month 6 and Month 12 post-surgery)
- Leg Pain(Initial discharge from hospital (on average 3 days post-surgery), Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery)
- Number of Secondary Interventions(Up to Month 24 post-surgery)
- ODI(Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery)
- Radiographic interbody fusion(Month 6 post-surgery)