Micronized dHACM vs. Saline in the Treatment of Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of micronized dehydrated human amnion chorion membrane as compared to the 0.9% Sodium Chloride Injection, USP placebo control for the treatment of knee osteoarthritis

Detailed Description
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Each subject will receive 1 injection (micronized dHACM or placebo) and be evaluated for efficacy and safety during a 12-month observation period. A second injection (open-label access to micronized dHACM) will be offered to all subjects at the 180-day, 270-day, and 365-day time points, it may only be used once. Blinding for the first injection treatment allocation will be maintained until the end of the study. Subjects who receive the open-label access treatment will continue to be followed for 180 days after this second injection, regardless of the time at which treatment was received.

Official Title
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A Phase 2B, Prospective, Double-blinded, Randomized Controlled Trial of the Micronized Dehydrated Human Amnion Chorion Membrane Injection as Compared to Saline Placebo Injection in the Treatment of Osteoarthritis of the Knee

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: Micronized dHACM
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 and ≤ 80 years Subject has a diagnosis of osteoarthritis (OA) defined as Grade 1 to 3 on the Kellgren Lawrence grading scale Subject is willing and able provide informed consent and participate in all procedures and follow-up evaluations necessary to complete the study Subject must have a VAS pain scale greater than 45 Exclusion Criteria: Subject has a diagnosis of osteoarthritis (OA) defined as Grade 4 on the Kellgren Lawrence grading scale BMI greater than 40 kg/m^2 Subject has active infection at the injection site Symptomatic OA of the contralateral knee or of either hip that is not responsive to acetaminophen (Tylenol®) and requires other therapy. Subject has rheumatoid arthritis, psoriatic arthritis, or have been diagnosed with any other disorders that is the primary source of their knee pain, including but not limited to: osteonecrosis, radiculopathy, bursitis, tendinitis, tumor, cancer Subject has documented history of gout or pseudo-gout Subject has autoimmune disease or a known history of having Acquired Immunodeficiency Syndromes (AIDS) or HIV Subject has received any of the following to the target knee: Intra-articular hyaluronic acid (HA) injection within 12 weeks prior to screening Steroid or platelet rich plasma (PRP) injection within 12 weeks prior to screening Has had or is planning to have major surgery or arthroscopy in the target knee within 26 weeks of treatment History of a total knee arthroplasty Subject has used an investigational drug, device or biologic within 12 weeks prior to treatment Subject has a history of immunosuppressive or chemotherapy in the last 5 years Subject has had prior radiation at the site Subject is currently taking anticoagulant therapy (excluding Plavix or Aspirin) Subject is pregnant or plans to become pregnant within 365 days of treatment Subject has any significant medical condition that, in the opinion of the Investigator, would interfere with protocol evaluation and participation Subject is a worker's compensation patient Subject is a prisoner

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Micronized dHACM<br>Injection of micronized dHACM | Biological: Micronized dHACM<br>* Injection of 40 mg micronized dehydrated human amnion chorion membrane (dHACM) suspended in 1 mL 0.9% Sodium Chloride, USP<br>|
| Placebo Comparator: Saline<br>Injection of 0.9% Sodium Chloride Injection, USP | Drug: Saline<br>* Injection of 1 mL 0.9% Sodium Chloride, USP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint: Change From Baseline in Visual Analog Scale (VAS) for Pain at 90 Days | Visual Analog Scale (VAS): 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain | 90 days | 
| Primary Efficacy Endpoint: Change From Baseline in Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 90 Days | Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: Pain (5 questions) Stiffness (2 questions) Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | 90 days | 
| Primary Safety Endpoint: Number of Participants With Adverse Events (AEs) | Number of Participants with At Least 1 Treatment Emergent Adverse Event (TEAE) Reported | 365 days | 
| Primary Safety Endpoint: Number of Participants With Serious Adverse Events (SAEs) | Number of Participants with At Least 1 Serious Treatment Emergent Adverse Event (TEAE) Reported | 365 days | 
| Primary Safety Endpoint: Number of Participants With Unanticipated Adverse Events | Number of Participants with At Least 1 Unanticipated Treatment Emergent Adverse Event (TEAE) Reported | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint: Change From Baseline in Visual Analog Scale (VAS) at 180 Days | Visual Analog Scale (VAS) : 0 to 100 mm horizontal visual analog scale with a higher score indicating greater pain | 180 days | 
| Secondary Endpoint:Change From Baseline in WOMAC at 180 Days | Western Ontario and McMaster Universities Arthritis Index (WOMAC) evaluation of Hip and Knee Osteoarthritis. Self-administered questionnaire consisting of 24 questions divided into 3 subscales: Pain (5 questions) Stiffness (2 questions) Physical Function (17 questions) The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score, with a possible total score range of 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. | 180 days |