Degenerative Disc Disease, Lumbar Spine Fusion, Spinal Stenosis Lumbar, Spinal Stenosis, Lumbar Region, Spondylolisthesis, Transforaminal Lumbar Interbody Fusion
Conditions
Keywords
ProteiOS, HCT/P, bone graft, spinal fusion, lumbar interbody fusion, growth factor, allograft, TLIF
Brief summary
This is a prospective, multicenter, randomized, controlled study evaluating Influx™ ProteiOS®, an allograft-derived growth factor product, in transforaminal lumbar interbody fusion (TLIF). Participants undergoing 1- to 2-level TLIF (L2-S1) are randomized 2:1 to receive ProteiOS or a control graft (local bone with optional cancellous chip augmentation, no ProteiOS). The primary objective is to determine whether the 12-month interbody fusion rate (assessed by CT using the Brantigan-Steffee-Fraser classification) with ProteiOS is non-inferior to control, using a 5-percentage-point non-inferiority margin. Patient-reported outcomes (ODI, VAS, EQ-5D-5L), safety, and healthcare utilization are also assessed. A separate exploratory cohort at one study site will evaluate the same outcomes in participants undergoing anterior lumbar interbody fusion (ALIF) with or without ProteiOS, without formal hypothesis testing.
Detailed description
Transforaminal lumbar interbody fusion (TLIF) is a widely used technique for degenerative lumbar spine pathology. Prospective, randomized evidence on fusion outcomes, patient-reported outcomes, safety, and healthcare utilization for ProteiOS in TLIF is currently limited to retrospective data. This study randomizes participants 2:1 to ProteiOS versus a within-category control (standard graft material, no ProteiOS), with central, blinded, independent radiographic review of CT and X-ray fusion outcomes. The primary endpoint is CT-confirmed interbody fusion (BSF-3) at 12 months, tested for non-inferiority (margin = 5 percentage points, assumed fusion rates 95% ProteiOS vs. 89% control, 80% power, one-sided α = 0.025, Farrington-Manning likelihood score method). Secondary endpoints include fusion at 6 and 24 months, X-ray-based interbody and posterolateral fusion assessment (Lenke classification for PLF), patient-reported outcomes at 3, 6, and 24 months, adverse events, and healthcare utilization
Interventions
OTHERAllograft-derived growth factor (ProteiOS®)
Allograft-derived growth factor product (ProteiOS®) containing endogenous osteoinductive, angiogenic, and chemoattractant proteins bound to a scaffold of choice
OTHERStandard of Care (SOC)
Local autograft with optional mineralized cancellous allograft chip augmentation
Sponsors
Isto Biologics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants and investigators/surgeons are not blinded (surgeon must know which graft material to use intraoperatively). The central imaging core laboratory (independent, board-certified musculoskeletal/neuroradiologists performing BSF fusion grading) is blinded to treatment arm, site identity, clinical status, and prior imaging.
Intervention model description
2:1 randomization to ProteiOS (treatment) vs. control within each of two surgical cohorts (TLIF, ALIF)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years, skeletally mature at time of surgery * Degenerative disease of the lumbar spine (L2-S1) requiring 1-2 level instrumented TLIF, with or without posterolateral fusion, as determined by the treating surgeon * For the ALIF study site only: degenerative disease of the lumbar spine (L2-S1) requiring 1-2 level instrumented ALIF * Radiographic evidence of degenerative lumbar disease on CT, MRI, or plain radiograph (decreased disc height, herniated nucleus pulposus, ligamentum flavum/annulus hypertrophy, facet arthrosis/osteophyte, spinal canal or foraminal stenosis, or vertebral translation \>3 mm) * Symptoms of low back pain, radiculopathy, or neurogenic claudication consistent with radiographic findings * Preoperative back pain ≥4 on a 0-10 VAS * Preoperative leg pain ≥3 on a 0-10 VAS, consistent with radiculopathy or neurogenic claudication * Preoperative ODI score ≥30 * Failure of ≥6 months non-operative treatment (may be waived for progressive neurological deficit, new/worsening motor weakness, bowel/bladder dysfunction, or cauda equina syndrome) * Willing and able to comply with follow-up schedule and provide written informed consent
Exclusion criteria
* Scheduled for surgery with synthetic bone grafts containing hydroxyapatite, tricalcium phosphate, or other radio-opaque material * BMI \>40 * Prior lumbar spine fusion surgery at a level currently scheduled for surgery * Malignancy or treatment for malignancy within the last 5 years (benign skin cancer permitted) * Osteoporosis/osteopenia (≤2.5 SD below age-matched mean) * Use of rhBMP-2 (Infuse) or other active biologics * Active or systemic infection, malignancy, or severe metabolic bone disease * Chronic steroid use (\>10 days) * Revision fusion at index levels * Participation in another interventional clinical study within 30 days of consent * Known pregnancy or intent to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Fusion Success (via Computed Tomography (CT) analysis) | 12 months | Percentage of participants achieving fusion success, defined as Brantigan-Steffee-Fraser (BSF) classification Grade 3 (solid fusion: trabecular bone bridging across ≥50% of the interbody fusion area) at the treated level(s), assessed by CT scan. BSF is a 3-grade classification ranging from Grade 1 (pseudarthrosis) to Grade 3 (solid fusion), with higher grade indicating better fusion status. |
| Patient Reported Outcome: Oswestry Disability Index (ODI) | 12 Months | Oswestry Disability Index (ODI), a 10-item questionnaire assessing functional disability due to low back pain (raw score converted to a percentage, range 0-100%; 0 = no disability, 100 = maximum disability; higher score = worse disability), assessed at 12 months; mean scores compared between treatment and control arms. |
| Patient Reported Outcome: Neurological | 12 Months | Neurological status: Percentage of participants with no new or worsening neurological deficit from baseline, assessed across three components: motor function (Medical Research Council \[MRC\] grading scale, range 0-5, higher score indicates greater strength), sensory function (graded as intact, diminished, or absent), and deep tendon reflexes (graded as absent, diminished, normal, or hyperreflexic). |
| Patient Reported Outcome: Visual Analog Scale (VAS) | 12 Months | Visual Analog Scale (VAS) for leg and back pain (range 0-10; 0 = no pain, 10 = worst pain imaginable; higher score = worse pain), assessed at 12 months; mean scores compared between treatment and control arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Reported Outcome: Neurological | 3, 6, 24 Months | Neurological status: Percentage of participants with no new or worsening neurological deficit from baseline, assessed across three components: motor function (Medical Research Council \[MRC\] grading scale, range 0-5, higher score indicates greater strength), sensory function (graded as intact, diminished, or absent), and deep tendon reflexes (graded as absent, diminished, normal, or hyperreflexic). |
| Patient Reported Outcome: Oswestry Disability Index (ODI) | 3, 6, 24 Months | Oswestry Disability Index (ODI), a 10-item questionnaire assessing functional disability due to low back pain (raw score converted to a percentage, range 0-100%; 0 = no disability, 100 = maximum disability; higher score = worse disability); mean scores compared between treatment and control arms. |
| Healthcare utilization: Frequency of Hospital Visits | Up to 24 months | Number of hospital visits per participant, up to 24 months. |
| Healthcare Utilization: Length of Hospital Stay | Up to 24 months | Duration of hospital stay per participant, in days, up to 24 months. |
| Patient Reported Outcome: Visual Analog Scale (VAS) | 3, 6, 24 Months | Visual Analog Scale (VAS) for leg and back pain (range 0-10; 0 = no pain, 10 = worst pain imaginable; higher score = worse pain); mean scores compared between treatment and control arms. |
| Healthcare Utilization: ICU Time | Up to 24 Months | Duration of ICU stay per participant, in days, up to 24 months. |
| Fusion (via Computed Tomography (CT)) | 6 and 24 months | Percentage of participants achieving fusion success, defined as Brantigan-Steffee-Fraser (BSF) classification Grade 3 (solid fusion: trabecular bone bridging across ≥50% of the interbody fusion area) at the treated level(s), assessed by CT scan. BSF is a 3-grade classification ranging from Grade 1 (pseudarthrosis) to Grade 3 (solid fusion), with higher grade indicating better fusion status. |
| Fusion (x ray) | 3, 6, 12, 24 months | Percentage of participants achieving fusion by X-ray. Interbody fusion (all participants): Brantigan-Steffee-Fraser (BSF) classification, Grade 1 (pseudarthrosis) to Grade 3 (solid fusion); success = Grade 3; higher grade = better. |
| Adverse Events | 24 months | Nature (descriptive) and frequency (number) of procedure and biologic related Adverse Events and Serious Adverse Events |
Outcome results
None listed