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

Degenerative Disc Disease Clinical Trial

— STRUCTURE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04294004
• Other study ID #: KUR-113/01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 27, 2020
• Est. completion date: July 30, 2025

Study information

• Verified date: August 2023
• Source: Kuros Biosurgery AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: July 30, 2025
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Written informed consent by the patient.

2. 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.

3. 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:

1. instability (angulation = 5 degrees or translation = 3 mm on flexion/extension radiographs),

2. osteophyte formation of facet joints or vertebral endplates,

3. decreased disc height by > 2 mm, but dependent upon the spinal level,

4. scarring/thickening of ligamentum flavum, annulus fibrosis or facet joint capsule,

5. disc degeneration and/or herniation,

6. facet degeneration,

7. vacuum phenomenon.

4. Patients with an Oswestry Disability Index (ODI) score = 35.

5. Patients with a Visual Analogue Scale (VAS) leg score = 40.

6. 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.

7. Patients willing to undergo PK sampling.

Exclusion Criteria:

1. Patients with open epiphyseal plates.

2. Patient requiring emergency spinal decompression or spinal fusion.

3. Patients requiring multilevel fusion or expected to need secondary intervention within one year following surgery.

4. Any prior fusion or attempted fusion at an adjacent level.

5. Any prior fusion or attempted fusion at the index level.

6. Pregnant or breast-feeding women.

7. Known or suspected allergies to any of the components of KUR-113 Bone Graft (e.g.

hypersensitivity to aprotinin).

8. Any prior use of teriparatide or abaloparatide or graft material containing PTH1-34.

9. Patients with hypercalcemic disorders (e.g., primary hyperparathyroidism).

10. Patients with Paget's Disease or unexplained high levels of alkaline phosphatase.

11. Prior radiation therapy involving bone.

12. 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.

13. Any medical condition requiring radiotherapy or immunosuppression.

14. History of thyroid autoimmune disease (Hashimoto's thyroiditis, Graves' disease) or hyperthyroidism.

15. Patients on chronic systemic steroids (i.e. > 14 consecutive days) within 6 months prior to Screening Visit.

16. Osteopenia (T score < -1.0) or osteoporosis of the spine (T score < -2.5).

17. DDD related to benign or malignant tumor.

18. History or presence of active malignancy.

19. Hereditary disorders predisposing to osteosarcoma.

20. Patients with invasive skin cancer.

21. Evidence of local or systemic infection.

22. Patients with known active COVID-19 disease.

23. Current smokers.

24. Type 1 diabetes (regardless of HbA1c) or Type 2 diabetes with a documented HbA1c > 7.0.

25. Any acute or chronic concurrent medical conditions that in the Investigator's opinion are a contraindication to the procedure and study participation.

26. 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).

27. 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.

28. Involved in active litigation relating to his/her spinal condition or workers compensation claimants.

29. BMI greater than 40.

Related Conditions & MeSH terms

• Degenerative Disc Disease
• Intervertebral Disc Degeneration
• Spinal Fusion

Intervention

Combination Product:
• TGplPTH1-34 in fibrin
TGplPTH1-34 within a fibrin matrix applied within and around a polyetheretherketone (PEEK) intervertebral cage

Other:
• Autologous Bone Graft
Local autograft collected from decompression which may be supplemented with iliac crest bone graft (ICBG) if local autograft is insufficient.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Justin Parker Neurological Institute	Boulder	Colorado
United States	Indiana Spine Group	Carmel	Indiana
United States	Northwestern University-Northwestern Memorial Hospital	Chicago	Illinois
United States	Orthopedic Associates of Michigan	Grand Rapids	Michigan
United States	University of California San Diego	La Jolla	California
United States	Hospital for Special Surgery	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	South Texas Spine Center	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Kansas Spine and Specialty Hospital	Wichita	Kansas
United States	University at Buffalo Neurosurgery	Williamsville	New York

Sponsors (3)

Lead Sponsor	Collaborator
Kuros Biosurgery AG	Avania, Kuros BioSciences B.V.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Radiographic interbody fusion	Determined by IREP using CT-scans	Month 6 post-surgery
Secondary	Radiographic posterolateral fusion	Determined by IREP using CT-scans	Month 6 and Month 12 post-surgery
Secondary	ODI	Change from baseline	Week 6, Month 3, Month 6, Month 12, and Month 24 post-surgery
Secondary	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
Secondary	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
Secondary	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