STAND - Study of the AGN1 LOEP SV Kit Compared to PMMA in Patients With Vertebral Compression Fractures

Study Overview
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Brief Summary
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This is a multicenter, single-blinded, randomized controlled clinical trial evaluating the safety and efficacy of the AGN1 LOEP SV Kit for the treatment of painful vertebral compression fragility fractures (VCFs). The objective of this study is to demonstrate non-inferiority of the AGN1 LOEP SV Kit for the treatment of VCFs to standard of care vertebroplasty treatment using bipedicular injection of PMMA bone cement.

Detailed Description
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Four hundred and eight (408) eligible subjects at up to twenty-five (25) study sites will be randomized 1:1 for treatment using the AGN1 LOEP SV Kit (Intervention Group) or PMMA bone cement (Active Control Group). Intervention Group - receives vertebral augmentation of the target VCF(s) using the AGN1 LOEP SV Kit Active Control Group - receives vertebral augmentation of the target VCF(s) using either Stryker VertaPlex HV or Medtronic Kyphon HV-R. Follow-up visits will be conducted at 7 days, 28 days, 3 months, 12 months and 24 months after the procedure.

Official Title
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A Randomized, Single-Blinded, Non-Inferiority Study Comparing AGN1 Local Osteo-Enhancement Procedure (LOEP) SV Kit Treatment of Vertebral Compression Fragility Fractures to PMMA Bone Cement Treatment

Conditions
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Vertebral Compression Fracture, Compression Fracture, Vertebral Compression

Intervention / Treatment
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* Device: Treatment Group: AGN1 LOEP SV Kit
* Device: Control Group: PMMA bone cement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a male or female 50 years of age or older at the time of study treatment. Subject has one (1) or two (2) acute VCF(s). Note that subjects are eligible if they have an asymptomatic, healed VCF(s) at any non-target vertebral level. Each target VCF meets all of the following criteria: Due to diagnosed or presumed underlying osteoporosis T1 to L5 inclusively Target VCF-related pain ≤ 6 months at time of study treatment Each target VCF shows loss of height of the vertebral body ≤ 50% based on X-ray at baseline. Each target VCF is acute or persistent (not healed), as demonstrated on imaging, including T2-weighted, STIR MRI, bone scan or bone scan with SPECT/CT, serial radiographs, or other serial imaging demonstrating acuity. Focal tenderness to palpation of the spinal process of each target VCF on the physical exam correlates with imaging. Subject has failed conservative medical therapy (bed rest, observation, chiropractic care, orthotics, opioid and non-opioid analgesics, and/or physical therapy), defined as either having a VAS back pain score of ≥ 70 mm after 24 hours to 6 weeks of conservative care or a VAS back pain score of ≥ 50 mm after more than 6 weeks of conservative care. Subject has an Oswestry Disability Index (ODI) score of ≥ 30% at baseline. Subject is capable of giving written informed consent to participate in the study. The subject's willingness, ability, and commitment to participate in screening, treatment, and all follow-up evaluations for the full length of the study has been documented Exclusion Criteria: At least one of the target VCF(s) is unstable, including split or burst fracture. Subject has a bleeding disorder. Subject has an active infection of the spine or surgical site. Subject has a bloodborne infection. At least one of the target VCFs is due to underlying or suspected tumor. At least one of the target VCFs is due to high-energy trauma. At least one of the target VCFs is due to osteonecrosis. At least one of the target VCFs has a local kyphotic angle of > 30 degrees, measured as the angle between the superior endplate and inferior endplate at the target VCF. Subject has had any prior surgical treatment at the target vertebral level or adjacent vertebral levels. The pedicle(s) in the target vertebral body appears unable to safely accommodate transpedicular access instrumentation. Subject has neurologic symptoms, deficits, or radiculopathy related to the target VCF(s). Subject has spinal canal compromise causing clinical manifestations of cord, neural foramen, or nerve root compression at the level to be treated. Subject has pain, progressive weakness, or paralysis due to herniated nucleus pulposus or spinal stenosis. Subject has spondylolisthesis > Grade 1 at target vertebral body(ies). Subject requires daily opioid medication for pain not related to the target VCF(s). Subject has severe cardiopulmonary deficiencies. Subject has a Body Mass Index (BMI) > 35. Subject has a history of metabolic bone disease other than osteoporosis (e.g., Paget's disease, renal osteodystrophy, or osteomalacia). Subject has a history of tuberculous spondylitis. Subject has a history of invasive malignancy within the last five (5) years, other than non-melanoma skin cancer. Subject is not excluded if they have a history of malignancy over 5 years ago treated with curative intent and without clinical signs or symptoms since then. Subject is on oral or parenteral immune-suppressive drugs. Subject has uncontrolled diabetes mellitus. Subject has severe renal insufficiency defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min. Subject has a diagnosed calcium metabolism disorder. Subject has known allergies to calcium-based bone void fillers. Subject is pregnant or planning to become pregnant during participation in the study. In the judgment of the Investigator, the subject is not a good study candidate. (e.g. substance abuse or chemical dependency, inability to adhere to follow-up schedule, progression of the fracture between screening and the procedure visit). Subject is currently enrolled in another interventional clinical study.

Ages Eligible for Study
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Minimum Age: 50 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
Interventional Model Description: Four hundred eight (408) eligible subjects at up to twenty-five (25) study sites will be randomized 1:1 for treatment using the AGN1 LOEP SV Kit (Intervention Group) or PMMA bone cement (Active Control Group).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with AGN1 LOEP SV Kit<br>The AGN1 LOEP SV Kit is intended for fixation of pathological fractures of the vertebral body using vertebral augmentation. Following saline lavage to create space, the AGN1 implant material is injected and hardens in situ to augment the fractured vertebral body. The AGN1 implant material is then resorbed and replaced with new bone. | Device: Treatment Group: AGN1 LOEP SV Kit<br>* The AGN1 LOEP SV Kit is intended for fixation of pathological fractures of the vertebral body using vertebral augmentation. Following saline lavage to create space, the AGN1 implant material is injected and hardens in situ to augment the fractured vertebral body. The AGN1 implant material is then resorbed and replaced with new bone.<br>|
| Active Comparator: Treatment with PMMA bone cement<br>High viscosity PMMA bone cement will be used for vertebral augmentation. | Device: Control Group: PMMA bone cement<br>* High viscosity PMMA bone cement will be used for vertebral augmentation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in VCF-related Pain as measured by a 100 mm Visual Analogue Scale (VAS) | Change in VCF-related pain by > 20 mm from baseline as measured by a 100 mm Visual Analogue Scale (VAS) where 0mm is no pain, and 100mm is worst pain possible. | 24 months | 
| Change in function | change of function from baseline as measured by the Oswestry Disability Index (ODI) | 24 months | 
| Radiographic evidence of implant resorption (Intervention Group only) | change in resorption from procedure as assessed by independent radiographer | 24 months | 
| Radiographic evidence of bone formation (Intervention Group only) | change in bone formation from procedure as assessed by independent radiographer | 24 months | 
| Adverse events | Occurrence of device-related serious adverse events, device-related adverse events or serious adverse events categorized as failure or surgical intervention at the target level occurring post-treatment | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LOEP, AGN1