Clinical trial NCT04378543: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Degenerative Spondylolisthesis
Keywords: spine
spondylolisthesis
degenerative disc disease
back pain
Lead sponsor: Ankasa Regenerative Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-07
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 2 weeks
measure: Safety and Tolerability
timeFrame: 8 weeks
measure: Safety and Tolerability
timeFrame: 26 weeks
measure: Safety and Tolerability
timeFrame: 52 weeks
measure: Safety and Tolerability
timeFrame: 104 weeks
Secondary outcomes:
measure: Rate of early fusion
timeFrame: 26 weeks
measure: Rate of fusion
timeFrame: 52 weeks
measure: Rate of fusion
timeFrame: 104 weeks
measure: Oswestry Disability Index
timeFrame: 8 weeks
measure: Oswestry Disability Index
timeFrame: 26 weeks
measure: Oswestry Disability Index
timeFrame: 52 weeks
measure: Oswestry Disability Index
timeFrame: 104 weeks
measure: Short Form-36 (SF-36)
timeFrame: 8 weeks
measure: Short Form-36 (SF-36)
timeFrame: 26 weeks
measure: Short Form-36 (SF-36)
timeFrame: 52 weeks
measure: Short Form-36 (SF-36)
timeFrame: 104 weeks
measure: Visual Analog Scale (VAS) Pain
timeFrame: 8 weeks
measure: Visual Analog Scale (VAS) Pain
timeFrame: 26 weeks
measure: Visual Analog Scale (VAS) Pain
timeFrame: 52 weeks
measure: Visual Analog Scale (VAS) Pain
timeFrame: 104 weeks
measure: Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10
timeFrame: 8 weeks
measure: Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10
timeFrame: 26 weeks
measure: Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10
timeFrame: 52 weeks
measure: Patient Reported Outcomes Measurement Information System (PROMIS) - Global 10
timeFrame: 104 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck School of Medicine, University of Southern California
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: Wexner Medical Center, The Ohio State University
state: Ohio
Study officials:
References: