Prospective Study of ProteiOS in Lumbar Interbody Fusion (TLIF)

Prospective, Multicenter Evaluation of ProteiOS® Allograft Derived Growth Factor in Transforaminal Lumbar Interbody Fusion (TLIF)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Degenerative Disc Disease; Spinal Stenosis Lumbar; Spondylolisthesis; Transforaminal Lumbar Interbody Fusion; Spinal Stenosis, Lumbar Region; Lumbar Spine Fusion
• Intervention / Treatment: Other: Allograft-derived growth factor (ProteiOS®); Other: Standard of Care (SOC)

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

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TLIF - ProteiOS (Treatment); Influx™ demineralized cortical fibers combined 1:1 with ProteiOS®, ≥50% of total graft volume per level (5-15 cc total), optional cancellous allograft chip augmentation. If PLF indicated: 100% cortical fiber graft + ProteiOS + local bone in Fibrant PAK containment bag.	Other: Allograft-derived growth factor (ProteiOS®); Allograft-derived growth factor product (ProteiOS®) containing endogenous osteoinductive, angiogenic, and chemoattractant proteins bound to a scaffold of choice
Active Comparator: TLIF - Control; 5-15 cc locally harvested autograft, optional mineralized cancellous allograft chip augmentation, no ProteiOS. If PLF indicated: cortical fiber graft + local bone in Fibrant PAK containment bag.	Other: Standard of Care (SOC); Local autograft with optional mineralized cancellous allograft chip augmentation
Experimental: ALIF - ProteiOS (Treatment); Same ProteiOS-based mixture as TLIF treatment arm	Other: Allograft-derived growth factor (ProteiOS®); Allograft-derived growth factor product (ProteiOS®) containing endogenous osteoinductive, angiogenic, and chemoattractant proteins bound to a scaffold of choice
Active Comparator: ALIF - Control; Same control graft composition as TLIF control arm	Other: Standard of Care (SOC); Local autograft with optional mineralized cancellous allograft chip augmentation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Fusion Success (via Computed Tomography (CT) analysis)	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.	12 months
Patient Reported Outcome: Oswestry Disability Index (ODI)	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.	12 Months
Patient Reported Outcome: Neurological	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).	12 Months
Patient Reported Outcome: Visual Analog Scale (VAS)	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.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fusion (via Computed Tomography (CT))	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.	6 and 24 months
Fusion (x ray)	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.	3, 6, 12, 24 months
Adverse Events	Nature (descriptive) and frequency (number) of procedure and biologic related Adverse Events and Serious Adverse Events	24 months
Patient Reported Outcome: Visual Analog Scale (VAS)	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.	3, 6, 24 Months
Patient Reported Outcome: Neurological	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).	3, 6, 24 Months
Patient Reported Outcome: Oswestry Disability Index (ODI)	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.	3, 6, 24 Months
Healthcare utilization: Frequency of Hospital Visits	Number of hospital visits per participant, up to 24 months.	Up to 24 months
Healthcare Utilization: Length of Hospital Stay	Duration of hospital stay per participant, in days, up to 24 months.	Up to 24 months
Healthcare Utilization: ICU Time	Duration of ICU stay per participant, in days, up to 24 months.	Up to 24 Months

Collaborators and Investigators

• Sponsor: Isto Biologics

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: August 11, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 20, 2026

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: allograft; bone graft; growth factor; spinal fusion; TLIF; lumbar interbody fusion; HCT/P; ProteiOS
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Spondylolysis; Spondylosis; Spinal Stenosis; Spondylolisthesis; Intervertebral Disc Degeneration; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: CS-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No