Safety Evaluation of ART352-L in Subjects Undergoing Posterolateral Spinal Fusion

Study Overview
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Brief Summary
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Ankasa Regenerative Therapeutics, Inc. (Ankasa) is developing ART352-L, a liposomal formulation of recombinant human Wnt3A protein, that is applied ex vivo, to harvested autologous bone grafts (autograft) to enhance the osteogenic properties of the autograft prior to reimplantation in orthopedic surgeries. This is a phase 1/2 open label safety evaluation of ART352-L treated autologous bone grafts in patients undergoing posterolateral lumbar spinal fusion to treat single level degenerative spondylolisthesis. The primary objective of the study is to evaluate the safety and tolerability of ART352-L treated local bone autografts in patients being treated for this condition, with the secondary objective to evaluate the rates of early and overall spinal fusion. Additionally, changes in patient mobility and quality of life measures from baseline following treatment with ART352-L will be evaluated.

Official Title
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A Phase 1b/2a Safety Evaluation of ART352-L in Subjects Undergoing Posterolateral Spinal Fusion

Conditions
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Degenerative Spondylolisthesis

Intervention / Treatment
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* Biological: ART352-L


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥50 years of age scheduled to undergo single level posterolateral lumbar spinal fusion surgery in conjunction with local autograft bone for degenerative spondylolisthesis Psychosocially, mentally, and physically able to fully comply with this protocol including the required follow-up visits, the filling out of required forms, and have the ability to understand and give written informed consent Willing and able to undergo diagnostic imaging, inclusive of X-rays and CT scans with contrast Persistent, disabling pain after at least 6 months of non-surgical intervention (e.g., anti-inflammatory medication, physical therapy, chiropractic care) prior to providing informed consent Pre-operative Oswestry Disability Index (ODI) Score ≥30 Grade 1 or less spondylolisthesis or retrolisthesis Absence of neurological motor deficit Agree to use a highly reliable method of birth control (male and female subjects) for at least 90 days after administration of Investigational Product (IP) - Women of childbearing potential must have a negative pregnancy test at screening and again ≤7 days prior to surgery. Perimenopausal women must be amenorrheic for at least 12 months prior to the time of providing informed consent to be considered of non-childbearing potential. Agree to remain nicotine-free for the duration of their participation in the study Exclusion Criteria: Multiple level spondylolistheses or a primary diagnosis of low back pain syndrome secondary to diseases other than degenerative spondylolisthesis Concurrent medications that affect bone homeostasis including, but not limited to, bisphosphonates Ongoing / existing infections in or around the surgical site or spine Prior lumbar spine arthrodesis Concurrent clinically significant autoimmune disorder or systemic inflammatory disease Known hypersensitivity to recombinant Wnt proteins Use of tobacco; subjects must be nicotine-free at screening and agree to remain nicotine free for the duration of the study Use of medications that may impair cell proliferation and bone healing including: chemotherapy, radiation, chronic steroids and immunosuppressive drugs. Note: Medications that may impair cell proliferation are to be discussed with the protocol medical monitor prior to enrollment Severe established osteoporosis requiring active treatment e.g., with bone density more than 2.5 standard deviations below the young adult mean with one or more osteoporotic fractures A Body Mass index (BMI) ≥ 40 unless documentation clearly demonstrates why BMI is not a primary factor in the subject's decreased mobility Chronic opioid use History of deep vein thrombosis (DVT) or blood clotting abnormalities Uncontrolled diabetes mellitus Pre-operative/anesthesia evaluations deeming the subject ineligible for surgery Female subjects who are pregnant or intend to become pregnant during the course of the study Male subjects, if not infertile or surgically sterilized, who will not agree to use highly-effective contraception or to not donate sperm from screening until at least 90 days after receiving IP Active malignancy ≤5 years prior to providing informed consent. EXCEPTIONS: Non-melanotic skin cancer, carcinoma-in-situ of the cervix. NOTE: If there is a history of prior malignancy, the subject must not be receiving other specific treatment for their cancer. Concurrent participation in another investigational drug, biologic or device study that could confound study data Involvement in or plans to engage in litigation or receiving Worker's Compensation related to neck, back, or leg pain

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ART252-L<br>local autologous bone graft will be treated ex vivo once with ART352-L prior to re-implantation into the site of spinal fusion | Biological: ART352-L<br>* recombinant human Wnt3a protein delivered on liposomes to local autologous bone graft during posterolateral fusion procedures<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Incidence of adverse events and adverse events of special interest | 2 weeks | 
| Safety and Tolerability | Incidence of adverse events and adverse events of special interest | 8 weeks | 
| Safety and Tolerability | Incidence of adverse events and adverse events of special interest | 26 weeks | 
| Safety and Tolerability | Incidence of adverse events and adverse events of special interest | 52 weeks | 
| Safety and Tolerability | Incidence of adverse events and adverse events of special interest | 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of early fusion | Rate of early fusion using Lenke scoring of computed tomography (CT) scans | 26 weeks | 
| Rate of fusion | Rate of fusion using Lenke scoring of CT scans | 52 weeks | 
| Rate of fusion | Rate of fusion using Lenke scoring of CT scans | 104 weeks | 
| Oswestry Disability Index | Change from baseline in Oswestry Disability Index | 8 weeks | 
| Oswestry Disability Index | Change from baseline in Oswestry Disability Index | 26 weeks | 
| Oswestry Disability Index | Change from baseline in Oswestry Disability Index | 52 weeks | 
| Oswestry Disability Index | Change from baseline in Oswestry Disability Index | 104 weeks | 
| Short Form-36 (SF-36) | Change from baseline in Short Form-36 (SF-36) score | 8 weeks | 
| Short Form-36 (SF-36) | Change from baseline in Short Form-36 (SF-36) score | 26 weeks | 
| Short Form-36 (SF-36) | Change from baseline in Short Form-36 (SF-36) score | 52 weeks | 
| Short Form-36 (SF-36) | Change from baseline in Short Form-36 (SF-36) score | 104 weeks | 
| Visual Analog Scale (VAS) Pain | Change from baseline in Visual Analog Scale (VAS) Pain assessment | 8 weeks | 
| Visual Analog Scale (VAS) Pain | Change from baseline in Visual Analog Scale (VAS) Pain assessment | 26 weeks | 
| Visual Analog Scale (VAS) Pain | Change from baseline in Visual Analog Scale (VAS) Pain assessment | 52 weeks | 
| Visual Analog Scale (VAS) Pain | Change from baseline in Visual Analog Scale (VAS) Pain assessment | 104 weeks | 
| Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10 | Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Global-10 Score | 8 weeks | 
| Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10 | Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Global-10 Score | 26 weeks | 
| Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10 | Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Global-10 Score | 52 weeks | 
| Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10 | Change from baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Global-10 Score | 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spine, spondylolisthesis, degenerative disc disease, back pain