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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ankle Osteoarthritis

Intervention / Treatment
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* Biological: Axolotl Ambient
* Drug: Drug/Placebo: 0.9% Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Willing to be randomized to either the investigational or control group Male or female at least 18 years of age and less than 80 Clinical diagnosis of symptomatic tibiotalar (ankle) OA (primary idiopathic OA or post-traumatic OA), modified K-L grade 1-3a One ankle is the most symptomatic lower extremity joint and the only lower extremity joint currently planned for treatment Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations 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 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 Chronic ankle pain for ≥ 6 months SAOS Pain score ≥ 30 and ≤ 80 and AOS Function score ≥ 30 and ≤ 80 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: 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. Modified K-L Grade 3b or 4 osteoarthritis of the index joint Diagnosis of ipsilateral peri-articular arthritis (e.g. subtalar joint) that the investigator determines may significantly confound the study results Received intra-articular hyaluronic acid injection in the index joint within the last 6 months Received intra-articular steroid injection in the index joint within the last 3 months Prior major surgical repair or reconstruction of the ankle that the investigator determines may significantly confound the study results Baseline pain catastrophizing score ≥ 23 Any surgery of the index ankle within the last 12 months Planned arthroscopy or other procedure on the ankle during the study Bilateral ankle OA requiring treatment of both ankles Pregnancy, breastfeeding, or woman of child-bearing potential not using adequate contraception Bone deficit Charcot foot disease Radiographic evidence of open epiphyses Systemic inflammatory condition Substantial vascular insufficiency Current treatment with anticoagulants Deformity in coronal, axial or sagittal plane greater the 30° Patients weighing less than 47 kg. BMI greater than 45 kg/m2 Documented medical history of, or radiographic evidence of, a bone disease (e.g. severe osteoporosis or avascular necrosis) or other condition (e.g., osteolysis) Comorbidity that would limit the ability to administer any functional measurements Has at the time of injection, a systemic or local infection at the site of injection 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) Known hypersensitivity to penicillin Known allergy to phenol red 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] Medical condition requiring radiation, chemotherapy or immunosuppression Have an active history of malignancy (except for basal cell carcinoma of the skin) 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 Has obvious or documented alcohol or illicit drug addictions Is a prisoner in a correctional institution/facility Actively involved in litigation or workman's compensation Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization Bedridden, confined to a wheelchair, or unable to walk 50 m without the help of a walker, crutches, or cane Is currently taking prescription pain medication for any conditions other than ankle osteoarthritis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Placebo-controlled, Double-blinded
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Single dose, 2.0 mL of 0.9% normal saline, administered via intra-articular injection administered to the affected tibiotalar joint. | Drug: Drug/Placebo: 0.9% Normal Saline<br>* Drug/Placebo: 0.9% Normal Saline<br>|
| Experimental: Investigational Group<br>Biological/Vaccine: Axolotl Ambient Axolotl Ambient is an allogeneic amniotic intraarticular injection therapy consisting of a growth factor and cytokine-rich fluid derived from human amnion cells. Other Names: • CA20 | Biological: Axolotl Ambient<br>* Axolotl Ambient is an allogeneic amniotic intra-articular injection therapy consisting of a growth factor and cytokine-rich fluid derived from human amnion cells.<br>* Other names: CA20;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving Composite Clinical Success | Changes from baseline to each follow-up timepoint (4 weeks, 3 and 6 months) will be calculated for each outcome metric and statistical significance of changes will be assessed through repeated measures ANOVA or a mixed effects model to accommodate missing data points. Two options (based on either AOS or FAOS scores) for CCS will be defined as: Improvement in AOS (Pain and Function, independently) or FAOS (Pain and ADL, independently) subdomain scores of at least 20% from baseline AND No medical or surgical intervention beyond allowed rescue medication AND Absence of treatment-related SAEs | 4 Weeks | 
| Proportion of patients achieving Composite Clinical Success | Changes from baseline to each follow-up timepoint (4 weeks, 3 and 6 months) will be calculated for each outcome metric and statistical significance of changes will be assessed through repeated measures ANOVA or a mixed effects model to accommodate missing data points. Two options (based on either AOS or FAOS scores) for CCS will be defined as: Improvement in AOS (Pain and Function, independently) or FAOS (Pain and ADL, independently) subdomain scores of at least 20% from baseline AND No medical or surgical intervention beyond allowed rescue medication AND Absence of treatment-related SAEs | 3 Months | 
| Proportion of patients achieving Composite Clinical Success | Changes from baseline to each follow-up timepoint (4 weeks, 3 and 6 months) will be calculated for each outcome metric and statistical significance of changes will be assessed through repeated measures ANOVA or a mixed effects model to accommodate missing data points. Two options (based on either AOS or FAOS scores) for CCS will be defined as: Improvement in AOS (Pain and Function, independently) or FAOS (Pain and ADL, independently) subdomain scores of at least 20% from baseline AND No medical or surgical intervention beyond allowed rescue medication AND Absence of treatment-related SAEs | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | An Adverse Event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in study subjects whether or not considered related to the investigational product. This definition includes events related to the investigational product or the comparator and events related to the procedures involved. | Baseline (Day 0) to 12 Months | 
| Symptoms, Quality of Life and Sports and Recreation subscales of the FAOS | The FAOS score was developed to reflect a foot and ankle version of the Knee Osteoarthritis Outcomes Score (KOOS). The FAOS score includes symptoms, quality of life and sports and recreation subscales. | Baseline (Day 0), 4 Weeks, 3 Months, 6 Months, and 12 Months | 
| Visual Analog Scale for average ankle pain and worst ankle pain | The Visual Analog Scale (VAS) is a measure of pain intensity. It is a continuous scale comprised of a horizontal visual analog scale anchored by two verbal descriptors (one for each symptom extreme). | Baseline (Day 0), 4 Weeks, 3 Months, 6 Months, and 12 Months | 
| EuroQOL-5 dimension-5 level quality of life scale | EQ-5D-5L is a self-completed health status questionnaire that assesses quality of life. | Baseline (Day 0), 4 Weeks, 3 Months, 6 Months, and 12 Months | 
| Pain Catastrophizing Scale | The pain catastrophizing scale (PCS) is a 13-item questionnaire that asks participants to grade each item on a 5-point scale. | Baseline (Day 0), 4 Weeks, 3 Months, 6 Months, and 12 Months | 
| Current Working Status | Percent of subject responses, for each of the following work status categories, by the treatment and control groups, at each timepoint. Current Working status, at each timepoint will be collected as: Not working, unrelated to ankle Not working, related to ankle Working with major limitations related to ankle Working without limitations related to ankle | Baseline (Day 0), 4 Weeks, 3 Months, 6 Months, and 12 Months | 
| Modified Kellgren and Lawrence Grade | The modified Kellgren and Lawrence Grade (K-L Grade) classifies osteoarthritis using five grades based on evaluation of x-ray of the affected joint. | Baseline (Day 0), 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Biologic, Amniotic Fluid