KUR-113 Bone Graft Versus Local Autograft for the Treatment of Single-level Transforaminal Lumbar Interbody Fusion

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Degenerative Disc Disease, Spinal Fusion

Intervention / Treatment
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* Combination Product: TGplPTH1-34 in fibrin
* Other: Autologous Bone Graft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 ≥ 35. Patients with a Visual Analogue Scale (VAS) leg score ≥ 40. 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. Exclusion Criteria: 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 PTH1-34. 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 > 7.0. 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KUR-113, Stage 1<br>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. | Combination Product: TGplPTH1-34 in fibrin<br>* TGplPTH1-34 within a fibrin matrix applied within and around a polyetheretherketone (PEEK) intervertebral cage<br>* Other names: KUR-113;|
| Active Comparator: Autologous Bone Graft<br>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. | Other: Autologous Bone Graft<br>* Local autograft collected from decompression which may be supplemented with iliac crest bone graft (ICBG) if local autograft is insufficient.<br>|
| Experimental: KUR-113, Stage 2<br>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. | Combination Product: TGplPTH1-34 in fibrin<br>* TGplPTH1-34 within a fibrin matrix applied within and around a polyetheretherketone (PEEK) intervertebral cage<br>* Other names: KUR-113;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic interbody fusion | 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). | Month 12 post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint | Radiographic interbody fusion using CT-scans, functional outcome (decrease of 15 points or more on Oswestry Disability Index (ODI)) and no post-surgical intervention to aid fusion or replace any of the spinal implants. | Month 6 and Month 12 post-surgery | 
| Radiographic interbody fusion | Determined by IREP using CT-scans | Month 6 post-surgery | 
| Radiographic posterolateral fusion | Determined by IREP using CT-scans | Month 6 and Month 12 post-surgery | 
| ODI | Change from baseline | Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery | 
| Leg Pain | Change from baseline using Visual Analogue Scale (VAS). VAS is scored from 0 to 100 with higher numbers being a worse outcome than a lower number. | Initial discharge from hospital (on average 3 days post-surgery), Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery | 
| Back Pain | Change from baseline using Visual Analogue Scale (VAS). VAS is scored from 0 to 100 with higher numbers being a worse outcome than a lower number. | 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 | Revisions, re-operations, removals, supplemental fixations, or any other procedure that adjusts or in any way removes part of the original implant configuration with or without replacement of the components | Up to Month 24 post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Fusion, Posterolateral Fusion, MagnetOs, Fibrin-PTH (KUR-113)