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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Degenerative Spondylolisthesis
• Intervention / Treatment: Biological: ART352-L

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Gloria Matthews, DVM, PhD; Phone Number: 404-947-6472; Email: gmatthews@wnt3.com
• Study Contact Backup: Name: Sanford Madigan, PhD; Email: smadigan@wnt3.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Keck School of Medicine, University of Southern California
      • Contact: Jeffrey Wang, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Brett Freedman, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Wexner Medical Center, The Ohio State University
      • Contact: Safdar Khan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. 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
3. Willing and able to undergo diagnostic imaging, inclusive of X-rays and CT scans with contrast
4. 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
5. Pre-operative Oswestry Disability Index (ODI) Score ≥30
6. Grade 1 or less spondylolisthesis or retrolisthesis
7. Absence of neurological motor deficit
8. 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.
9. Agree to remain nicotine-free for the duration of their participation in the study

Exclusion Criteria:

1. Multiple level spondylolistheses or a primary diagnosis of low back pain syndrome secondary to diseases other than degenerative spondylolisthesis
2. Concurrent medications that affect bone homeostasis including, but not limited to, bisphosphonates
3. Ongoing / existing infections in or around the surgical site or spine
4. Prior lumbar spine arthrodesis
5. Concurrent clinically significant autoimmune disorder or systemic inflammatory disease
6. Known hypersensitivity to recombinant Wnt proteins
7. Use of tobacco; subjects must be nicotine-free at screening and agree to remain nicotine free for the duration of the study
8. 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
9. 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
10. A Body Mass index (BMI) ≥ 40 unless documentation clearly demonstrates why BMI is not a primary factor in the subject's decreased mobility
11. Chronic opioid use
12. History of deep vein thrombosis (DVT) or blood clotting abnormalities
13. Uncontrolled diabetes mellitus
14. Pre-operative/anesthesia evaluations deeming the subject ineligible for surgery
15. Female subjects who are pregnant or intend to become pregnant during the course of the study
16. 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
17. 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.
18. Concurrent participation in another investigational drug, biologic or device study that could confound study data
19. Involvement in or plans to engage in litigation or receiving Worker's Compensation related to neck, back, or leg pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ART252-L; 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; recombinant human Wnt3a protein delivered on liposomes to local autologous bone graft during posterolateral fusion procedures

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ankasa Regenerative Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 30, 2020
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): October 1, 2023

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (ACTUAL): May 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: back pain; spine; spondylolisthesis; degenerative disc disease
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spondylolysis; Spondylosis; Spondylolisthesis
• Other Study ID Numbers: ART-SPF-ART352L-001

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