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

Degenerative Spondylolisthesis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04378543
• Other study ID #: ART-SPF-ART352L-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 30, 2020
• Est. completion date: October 2023

Study information

• Verified date: October 2020
• Source: Ankasa Regenerative Therapeutics, Inc.
• Contact: Gloria Matthews, DVM, PhD
• Phone: 404-947-6472
• Email: gmatthews[@]wnt3.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: October 2023
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Degenerative Spondylolisthesis
• Spondylolisthesis

Intervention

Biological:
• ART352-L
recombinant human Wnt3a protein delivered on liposomes to local autologous bone graft during posterolateral fusion procedures

Locations

Country	Name	City	State
United States	Wexner Medical Center, The Ohio State University	Columbus	Ohio
United States	Keck School of Medicine, University of Southern California	Los Angeles	California
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Ankasa Regenerative Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	Incidence of adverse events and adverse events of special interest	2 weeks
Primary	Safety and Tolerability	Incidence of adverse events and adverse events of special interest	8 weeks
Primary	Safety and Tolerability	Incidence of adverse events and adverse events of special interest	26 weeks
Primary	Safety and Tolerability	Incidence of adverse events and adverse events of special interest	52 weeks
Primary	Safety and Tolerability	Incidence of adverse events and adverse events of special interest	104 weeks
Secondary	Rate of early fusion	Rate of early fusion using Lenke scoring of computed tomography (CT) scans	26 weeks
Secondary	Rate of fusion	Rate of fusion using Lenke scoring of CT scans	52 weeks
Secondary	Rate of fusion	Rate of fusion using Lenke scoring of CT scans	104 weeks
Secondary	Oswestry Disability Index	Change from baseline in Oswestry Disability Index	8 weeks
Secondary	Oswestry Disability Index	Change from baseline in Oswestry Disability Index	26 weeks
Secondary	Oswestry Disability Index	Change from baseline in Oswestry Disability Index	52 weeks
Secondary	Oswestry Disability Index	Change from baseline in Oswestry Disability Index	104 weeks
Secondary	Short Form-36 (SF-36)	Change from baseline in Short Form-36 (SF-36) score	8 weeks
Secondary	Short Form-36 (SF-36)	Change from baseline in Short Form-36 (SF-36) score	26 weeks
Secondary	Short Form-36 (SF-36)	Change from baseline in Short Form-36 (SF-36) score	52 weeks
Secondary	Short Form-36 (SF-36)	Change from baseline in Short Form-36 (SF-36) score	104 weeks
Secondary	Visual Analog Scale (VAS) Pain	Change from baseline in Visual Analog Scale (VAS) Pain assessment	8 weeks
Secondary	Visual Analog Scale (VAS) Pain	Change from baseline in Visual Analog Scale (VAS) Pain assessment	26 weeks
Secondary	Visual Analog Scale (VAS) Pain	Change from baseline in Visual Analog Scale (VAS) Pain assessment	52 weeks
Secondary	Visual Analog Scale (VAS) Pain	Change from baseline in Visual Analog Scale (VAS) Pain assessment	104 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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