pAF for the Treatment of Osteoarthritis

Study Overview
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Brief Summary
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This is a Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis

Detailed Description
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This study will look at blinded standard of care (SOC) steroid injection vs. amniotic fluid injection (pAF) to treat and reduce osteoarthritis (OA) inflammation and pain. The main objectives of this study are to establish the safety and tolerability of allogeneic intra-articular pAF injections. Secondary objectives include pain levels and functional outcome scoring in patients over a 12 month time frame.

Official Title
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A Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Biological: Amniotic Fluid Injection
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are between the ages of 18-70 years A confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings consistent with Kellgren-Lawrence Stage 2-3 disease Patients who have failed conservative treatment (e.g. steroid, activity modification, therapy, etc.) within 3 months Unilateral or bilateral chronic knee joint pain >4 months Patients who are able to ambulate (i.e. not wheelchair bound) Patient reported a typical pain of at least 4 out of 10 during the past week using VAS numeric pain scale (0-10) Patients who are of childbearing potential must agree to use adequate contraception for 90 days after study drug injection Exclusion Criteria: Subjects who have had a previous injection (i.e. steroid, platelet rich plasma, or other) within the last 3 months A focal chondral defect, defined by x-ray evaluation BMI >40 as defined by NIH Clinical Guidelines Body Mass Index Concurrent participation in another investigational trial involving systemic administration of agents (within the previous 30 days) or plans to participate in any other allogeneic stem cell therapy trial during the 12 month follow-up period Clinical suspicion of infection at injection site Any surgeries within 4 weeks, other than diagnostic surgery Insulin or self-reported non-insulin dependent diabetic evident of HgA1c ≥8% among known diabetics Unable to consent to an English Language Consent Form Frank mechanical issues (i.e. locking of the knee) Workman's Compensation cases Rheumatoid arthritis Patients with a known allergy to local anesthetics or components of the study drug (pAF or steroid injection) Patients with vascular claudication or neurologic disorders affecting the index lower limb Patients with inflammatory arthropathies or connective tissue disorders; or Patients with known alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or have used medical marijuana within 7 days of study enrollment Patients with history of active cancer/malignancy within 2 years of screening, apart from adequately treated basal cell or squamous cell carcinoma of the skin not associated with the target knee Women who are nursing or pregnant Patients of childbearing potential who are unwilling to use adequate contraception for 90 days after study drug injection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amniotic Fluid Injection<br>Amniotic Fluid Injection, 3ml, one time dose. | Biological: Amniotic Fluid Injection<br>* Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis<br>* Other names: Human Amniotic Fluid, hAF;|
| Active Comparator: Standard of Care Steroid Injection<br>Corticosteroids, 3ml, one time dose. | Other: Standard of Care<br>* Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis<br>* Other names: Corticosteriods 3ml, one time dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repeat allogeneic intra-articular injection within 6 months. | Participants in both the SOC and pAF treatment arms may require and/or request rescue medication (i.e. SOC injection) at any time and will be given per PI discretion as part of standard of care. The clinicians will not know which study arm the study participant is in but will treat the participant with the SOC injection. This information will be documented and collected in the Electronic Medical Record (EMR), as well as the study's electronic data capture system. Participants will not be given any additional pAF injections throughout the study period. The participant will continue to be treated with SOC injections as needed. The outcome will be an indicator of whether or not a subject received a rescue medication within 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | Scale 0-100, where higher numbers indicate less problems. The KOOS is a survey that assesses joint symptoms, pain, pain during daily activities, physical function in daily living, as well as physical function during sports or recreational activities. | 6 months | 
| Visual Analog Scale for pain (VAS Pain) | Scale 0-10, where higher numbers indicate more pain. Pain will be measured by the Visual Analog Scale for pain (VAS Pain). This will consist of a comparison of mean values for VAS scoring scales pre-injection and at the 6 month follow-up assessment. Clinically significant outcomes will be determined based on the minimal clinically important difference (MCID) occurring for each respective scale, which is defined as the smallest reported measurement tool used to quantify perceived level of pain, graded on a scale from 0 to 10 with 0 representing no pain and 10 representing the worse pain possible, and with precise measurement of the marked pain level's distance from 0 comprising the pain level. | 6 months | 
| Single Assessment Numerical Evaluation (SANE) | Scale 0-100, where higher numbers indicate more pain. The SANE asks the patient to evaluate their percentage of normal on the affected joint of region of interest. This is a one-question survey. | 6 months | 
| Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT) | Scale 0-100, where higher numbers indicate better physical functioning. The PF-CAT is a bank of questions related to physical function. It is a computerized adaptive test that asks the patient to self-report capabilities rather than actual performance of physical activities. It includes functioning of upper extremities, lower extremities, and central regions and also assess instrumental activities of daily living, such as running errands. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteo Arthritis, Amniotic Fluid