Patient and evaluator blinded non-inferiority study on safety, tolerability and lumbar fusion efficacy of a single administration of Osteogrow (rhBMP6 in autologous blood coagulum (ABC) carrier) in adult patients treated by posterolateral lumbar interbody fusion (PLIF) for degenerative disc disease

INTERVENTION: Product Name: Osteogrow Product Code: rhBMP6 Pharmaceutical Form: Powder and solvent for implantation paste INN or Proposed INN: Not yet available Current Sponsor code: rhBMP6 Other descriptive name: RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ CONDITION: Lumbar spine single segment destabilization caused by degenerative disc disease ; MedDRA version: 20.0 Level: PT Classification code 10050505 Term: Spinal fusion surgery System Organ Class: 10042613 ‐ Surgical and medical procedures Therapeutic area: Body processes [G] ‐ Bones and nerves physological processes [G11] SECONDARY OUTCOME: Secondary end point(s): Superiority in the primary endpoint of either Osteogrow+Allograft group over the control group at 24 months after surgery and to demonstrate non‐inferiority (and possibly superiority) in the individual effectiveness variables (radiographic fusion and Oswestry pain/disability status), as well as maintenance or improvement in neurological status. Superiority is expected to be established in at least fusion success rate (radiological success). Timepoint(s) of evaluation of this end point: Patients will be evaluated preoperatively (within 6 months of surgery), intra‐operatively, and postoperatively at 3 and 6 weeks, 3, 6, 12, and 24 months. Fusion will be evaluated at 6, 12, and 24 months. Complications and adverse events will be evaluated over the course of the clinical trial. The protocol also includes plasma measurements of antibodies to rhBMP6 screening in both investigational and control patients pre‐operatively and at 3, 6, and 12 months. At each evaluation time‐point, the primary and secondary clinical and radiographic outcome parameters will be assessed. Success will be determined from data collected during the initial 24 months of follow‐up. INCLUSION CRITERIA: Patients meeting ALL of the following criteria at screening will be eligible for participation in the study: 1. Willing and able to provide informed consent. A signed informed consent form must be provided before any study assessments are done. Patients must be fluent in the language that is spoken by the investigator and the trial staff and in which the informed consent is written. 2. Male or female, age =18 years. Females of childbearing potential must be using a highly effective method of birth control within 2 years following surgery and must have a negative urine pregnancy test prior to the randomization. 3. Degenerative disc disease (DDD) of L3‐S1 segment accompanied by back pain of corresponding segment, with or without leg pain, with degeneration of the disc confirmed by patient history and radiographic analyses. Patients are non‐responsive to conservative treatment (e.g., bed rest, physical therapy, medications, spinal injections, manipula PRIMARY OUTCOME: Main Objective: Evaluate safety and composite endpoint non‐inferiority of two doses of Osteogrow+Allograft delivered bilaterally between transverse processes of a single lumbar spine segment in comparison to autologous iliac crest bone graft (with a non‐inferiority absolute margin of 10% as patient success at 24 months after surgery) Primary end point(s): Composite endpoint non‐inferiority of two doses of Osteogrow+Allograft delivered bilaterally between transverse processes of a single lumbar spine segment in comparison to autologous iliac crest bone graft (with a non‐inferiority margin of 10 percentage (%) points absolute difference) in the primary endpoint (patient success) at 24 months after surgery.; Safety outcomes ‐ Safety assessment will be based on clinical signs, vital signs assessments, laboratory assessments, spontaneously reported adverse events defined as absence of "implant associated or implant/surgical procedure associated" adverse events and freedom from additional surgical intervention defined as revision, non‐elective removal or supplemental fixation/fusion at the affected level. Local safety/tolerability will be assessed by clinical inspection (e.g., signs of inflammation), pain and functional assessment, and radiological assessment with a particular focus on possible distant soft tissue ossification.; Lumbar spine fusion efficacy ‐ Individual patient success (i.e., overall success) will be determined at 24 months and will be defined as a composite endpoint. A patient will be considered a success if all of the following criteria regarding safety and efficacy will be met: ; 1. Fusion defined as: evidence of bridging trabecular bone (continuous bony connection from superior transverse process to the inferior transverse process on both sides, based on radiographs and CT scans, no evidence of motion, no more than 3 mm difference in translation on lateral flexion/extension radiographs, less than 5° difference in angular motion between flexion and extension. Fusion outcomes will be used to indicate radiographic success.; 2. Function defined as: improvement of at least 15 points on the Oswestry Disability Index (ODI, version 2) graded on a 100 point scale as compared to baseline ; 3. Maintenance or improvement in neurological status with no new permanent neurological deficits as compared to baseline.; Secondary Objective: Demonstrate the fusion success superiority of a single administration of Osteogrow+Allograft delivered bilaterally between transverse processes of a single lumbar spine segment. ; Explore improvement and show superiority in ODI, pelvic pain (autologous bone donor site), general health status and patient satisfaction Explore the rhBMP6 antibody level in plasma. ; Timepoint(s) of evaluation of this end point: Patients will be evaluated preoperatively (within 6 months of surgery), intra‐operatively, and postoperatively at 3 and 6 weeks, 3, 6, 12, and 24 months. Fusion will be evaluated at 6, 12, and 24 months. Complications and adverse events will be evaluated over the course of the clinical trial. The protocol also includes plasma measurements of antibodies to rhBMP6 screening in both investigational and control patients pre‐operatively and at 3, 6, and 12 months. At each evaluation time‐point, the primary and secondary clinical and radiographic outcome parameters will be assessed. Success will be determined from data collected during the initial 24 months of follow‐up.;