Ankle Osteoarthritis
Conditions
Keywords
Osteoarthritis, Biologic, Amniotic Fluid
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALAxolotl Ambient
Axolotl Ambient is an allogeneic amniotic intra-articular injection therapy consisting of a growth factor and cytokine-rich fluid derived from human amnion cells.
DRUG"Drug/Placebo: 0.9% Normal Saline"
"Drug/Placebo: 0.9% Normal Saline"
Sponsors
Axolotl Biologix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Subjects, investigators, and outcome assessors will be blinded to the treatment allocation until completion of the 6-month follow-up visit.
Intervention model description
Randomized, Placebo-controlled, Double-blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ankle Osteoarthritis Scale (AOS; 48 hr Recall) Pain Subscale | 4-weeks, 3-months, and 6-months | The Ankle Osteoarthritis Scale (AOS) pain subscale goes from 0 (No pain) -100 (The worst imaginable). |
| Change From Baseline for Ankle Osteoarthritis Scale (AOS; 48 hr Recall) Function Subscale | 4-week, 3 Months, 6-months | The Ankle Osteoarthritis Scale (AOS) functions subscale goes from 0 (No difficulty) -100 (So difficult, unable). |
| Change From Baseline for Foot and Ankle Outcome Score (FAOS) for Pain Subscale | 4-weeks, 3-months, 6-months | A score of 100 represents no pain. A score of 0 constant pain. |
| Change From Baseline for Foot and Ankle Outcome Score (FAOS) for Function Subscale | 4-weeks, 3-months, 6-months | 100 represents perfect health and 0 represents extreme problems and complete functional limitation. . |
| Proportion of Patients Achieving Composite Clinical Success (CCS). | 4-weeks, 3-months, 6-months | CCS defined as a patient meeting all of the three following criteria: 1. Improvement in AOS (Pain and Function) or FAOS scores (Pain and ADL) of at least 20% from baseline 2. No surgical intervention or prescription pain medications for ankle OA 3. No treatment or procedure-related serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Post-procedure follow-up assessments: 4 weeks (+/-7days), 3 Months (+/- 14 days), 6 Months (+/- 30 days), 12 Months (+/- 60 days), and unscheduled visits (up to 19 months) | Proportion of subjects experiencing at least (1) adverse events. |
| FAOS Subscales Quality of Life (QoL) | 4-week, 3-month, 6-month | 0 (most severe problems) to 100 (no problems/best possible qualify of life) |
| Visual Analog Scale (VAS) for Ankle Pain (Average During Last 48 Hours) | 4 weeks, 3-months, 6-months | 100 millimeter scale 0mm - No Pain and 100mm - Worst Imaginable Pain |
| VAS Ankle Pain (Worst During Last 48 Hours) | 4-weeks, 3-months, 6-months | 100 millimeter scale 0mm - No Pain and 100mm - Worst Imaginable Pain |
| EuroQOL-5 Dimension-5 Level (EQ-5D-5L) Quality of Life Scale | 4-weeks, 3-months, 6-months | 0 to 100 scale - 0 the worst health you can imagine to 100 the best health you can imagine. |
| Working Status | Baseline, 4-weeks, 3-months, 6-months | Not working, unrelated to ankle Not working, related to ankle Working with major limitations related to ankle Working without limitations related to ankle |
| K-L Grade From Weightbearing X-ray at Baseline and 6 Months | Baseline, 6-months | Grade 2 Definite osteophytes with mild to moderate joint space narrowing; early radiographic OA Grade 3a Significant osteophytes and joint space narrowing, but greater than 50% of the joint space remains preserved Grade 3b Severe joint space narrowing with less than 50% remaining joint space, approaching end-stage disease but not completely bone-on-bone Grade 4 Near complete or complete loss of joint space with substantial deformity (end-stage OA) |
Countries
United States
Contacts
STUDY_DIRECTORRobert S. Kellar, PhD
Chief Science Officer (CSO)
STUDY_DIRECTORAaron J. Tabor, PhD, CTBS
V.P. of Clinical Operations
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 6 participants |
| Sex/Gender, Customized Male or Female | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
None listed