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

• ClinicalTrials.gov Identifier: NCT04378543
• Recruitment Status: Recruiting
• First Posted: May 7, 2020
• Last Update Posted: October 12, 2020
• Sponsor: Ankasa Regenerative Therapeutics, Inc.
• Information provided by (Responsible Party): Ankasa Regenerative Therapeutics, Inc.

Tracking Information

• First Submitted Date: April 30, 2020
• First Posted Date: May 7, 2020
• Last Update Posted Date: October 12, 2020
• Actual Study Start Date: September 30, 2020
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 4, 2020)

• Safety and Tolerability [ Time Frame: 2 weeks ]
  Incidence of adverse events and adverse events of special interest
• Safety and Tolerability [ Time Frame: 8 weeks ]
  Incidence of adverse events and adverse events of special interest
• Safety and Tolerability [ Time Frame: 26 weeks ]
  Incidence of adverse events and adverse events of special interest
• Safety and Tolerability [ Time Frame: 52 weeks ]
  Incidence of adverse events and adverse events of special interest
• Safety and Tolerability [ Time Frame: 104 weeks ]
  Incidence of adverse events and adverse events of special interest

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 4, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Degenerative Spondylolisthesis

Intervention

Biological: ART352-L

recombinant human Wnt3a protein delivered on liposomes to local autologous bone graft during posterolateral fusion procedures

Study Arms

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

Intervention: Biological: ART352-L

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 4, 2020): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gloria Matthews, DVM, PhD; 404-947-6472; gmatthews@wnt3.com

Contact: Sanford Madigan, PhD; smadigan@wnt3.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04378543
• Other Study ID Numbers: ART-SPF-ART352L-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ankasa Regenerative Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ankasa Regenerative Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ankasa Regenerative Therapeutics, Inc.
• Verification Date: October 2020