Evaluating Intra-articular Injection of Axolotl Ambient Compared to Saline in Subjects With Ankle Osteoarthritis

A Double-blind, Multi-Center, Prospective, Randomized Placebo-controlled Pilot Study Evaluating Intra-articular Injection of Axolotl Ambient Compared to Saline in Subjects with Ankle Osteoarthritis. The goal of this pilot study and subsequent pivotal trial is to evaluate the safety and effectiveness of Axolotl Ambient intra-articular injection for ameliorating the pain and dysfunction associated with ankle OA.

This pilot study is a double-blind multi-center, prospective, randomized, placebo-controlled trial. Upon randomization, patients will receive 1 intraarticular injection of the investigational product or control fluid. Follow-up will be conducted at 4 weeks, 3 and 6 months, with 6 months serving as the primary endpoint. The primary outcomes will consist of patient reported outcomes of pain and functional assessment by the physician, specific to the foot and ankle. Subjects will be monitored for an additional 6 months to establish safety over a 1-year follow-up and evaluate the durability of benefit.

Eligibility Criteria:
Inclusion Criteria:

1. Signed written informed consent
2. Willing to be randomized to either the investigational or control group
3. Male or female at least 18 years of age and less than 80
4. Clinical diagnosis of symptomatic tibiotalar (ankle) OA (primary idiopathic OA or post-traumatic OA), modified K-L grade 1-3a
5. One ankle is the most symptomatic lower extremity joint and the only lower extremity joint currently planned for treatment
6. Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations
7. For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and on the day of procedure, prior to injection
8. Male and female trial participants must commit to adequate birth control (e.g., surgically sterilized, oral contraceptive, two methods of barrier birth control, or abstinence) through the final follow-up
9. Chronic ankle pain for ≥ 6 months
10. SAOS Pain score ≥ 30 and ≤ 80 and AOS Function score ≥ 30 and ≤ 80
11. Willing to discontinue all prescription and over-the-counter pain medications being used for ankle OA symptoms for the duration of the study, except for acetaminophen, which is not allowed for the 3 days preceding each scheduled follow-up visit and the day of the follow-up visit.

Exclusion Criteria:

1. Previously received intra-articular injections in the index joint of Axolotl Ambient, bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), or other biologic-based products within the last 12 months.
2. Modified K-L Grade 3b or 4 osteoarthritis of the index joint
3. Diagnosis of ipsilateral peri-articular arthritis (e.g. subtalar joint) that the investigator determines may significantly confound the study results
4. Received intra-articular hyaluronic acid injection in the index joint within the last 6 months
5. Received intra-articular steroid injection in the index joint within the last 3 months
6. Prior major surgical repair or reconstruction of the ankle that the investigator determines may significantly confound the study results
7. Baseline pain catastrophizing score ≥ 23
8. Any surgery of the index ankle within the last 12 months
9. Planned arthroscopy or other procedure on the ankle during the study
10. Bilateral ankle OA requiring treatment of both ankles
11. Pregnancy, breastfeeding, or woman of child-bearing potential not using adequate contraception
12. Bone deficit
13. Charcot foot disease
14. Radiographic evidence of open epiphyses
15. Systemic inflammatory condition
16. Substantial vascular insufficiency
17. Current treatment with anticoagulants
18. Deformity in coronal, axial or sagittal plane greater the 30°
19. Patients weighing less than 47 kg.
20. BMI greater than 45 kg/m2
21. Documented medical history of, or radiographic evidence of, a bone disease (e.g. severe osteoporosis or avascular necrosis) or other condition (e.g., osteolysis)
22. Comorbidity that would limit the ability to administer any functional measurements
23. Has at the time of injection, a systemic or local infection at the site of injection
24. Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease)
25. Known hypersensitivity to penicillin
26. Known allergy to phenol red
27. Currently receiving treatment with a drug known to interfere with bone or cartilage metabolism \[e.g., systemic steroid therapy (topical steroid therapy is permissible), methotrexate\]
28. Medical condition requiring radiation, chemotherapy or immunosuppression
29. Have an active history of malignancy (except for basal cell carcinoma of the skin)
30. Has a history of autoimmune disease known to affect bone or cartilage. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, rheumatoid arthritis, Grave's disease, and Hashimoto's thyroiditis
31. Has obvious or documented alcohol or illicit drug addictions
32. Is a prisoner in a correctional institution/facility
33. Actively involved in litigation or workman's compensation
34. Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization
35. Bedridden, confined to a wheelchair, or unable to walk 50 m without the help of a walker, crutches, or cane
36. Is currently taking prescription pain medication for any conditions other than ankle osteoarthritis.