A Study to Evaluate the Efficacy of Amniotic Suspension Allograft in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This study is being conducted to evaluate the efficacy and safety of ASA compared to placebo in the management of osteoarthritis (OA) symptoms of the knee.

Detailed Description
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This is a prospective, multicenter, randomized, double-blind, placebo-controlled Phase 3 study of ASA in patients with OA of the knee. Initially, 474 subjects are planned for inclusion in this study using a group sequential design with an interim analyses and a final analysis. Patients will be randomly assigned in a 1:1 ratio to receive a single intra-articular (IA) injection of 2 mL of ASA (plus 2 mL of normal saline) or 4 mL of normal saline on Day 1. They will have serial assessments of knee pain, function, and symptoms scores, as well as safety assessments for up to 52 weeks after administration of the study drug.

Official Title
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A Phase 3 Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy of Amniotic Suspension Allograft (ASA) in Patients With Osteoarthritis of the Knee

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: Amniotic Suspension Allograft
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 18 years of age or older Diagnosis of OA of the index knee by a combination of clinical and radiographic findings. OA of the index knee with Kellgren and Lawrence radiographic classification (Grades 2-4 inclusive), Patients who have failed to adequately respond for at least 6 months to at least two osteoarthritis therapies within the last 12 months Overall index knee pain score above minimum required WOMAC Pain scale. Body mass index < 40 kg/m2 Using birth control, sterile or post-menopausal. Able to understand and provide written informed consent Exclusion Criteria: Kellgren and Lawrence radiographic grade 1 OA of the knee Use of pain medication less than 5 days before the baseline visit Regular use of anticoagulants Symptoms that could indicate meniscal displacement or an IA loose body. Corticosteroid injection into the index knee within 3 months prior to screening. Viscosupplement or any other autologous or allogeneic product into the index knee within 6 months prior to screening. Patients with known hypersensitivity reactions to ASA or any of its constituents. Knee surgery on the index knee within 12 months prior to screening and/or planned knee surgery during the study Knee surgery on the contralateral knee within 6 months prior to screening and/or planned knee surgery during the study Acute index knee trauma within 3 months prior to screening Knee effusion requiring aspiration of the index or contralateral knee within 3 months prior to screening. Contralateral knee pain above limits defined in the protocol Current therapy with any immunosuppressive therapy or medical conditions likely to require systemic steroids during the study. Any active or systemic infection including infection of the index knee joint or breakdown or disease of the index knee skin/soft tissues. Clinically significant intercurrent illness, medical condition, non-knee pain, or medical history that would jeopardize patient safety, limit participation, or compromise interpretation of data derived from the patient Active alcohol or substance use disorder, or any other reason that would make it unlikely that the patient will comply with study procedures Females who are pregnant or lactating Participation in another clinical trial within the 30 days (or 5 half-lives of the investigational compound, whichever is longer) before screening.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a prospective, multicenter, randomized, double-blind, placebo-controlled study of ASA in patients with OA of the knee. Patients will be randomly assigned in a 1:1 ratio to receive a single IA injection of 2 mL of ASA (plus 2 mL of normal saline) or 4 mL of normal saline.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASA<br>Participants receive a single IA injection of 2 mL of ASA (plus 2 mL of normal saline) | Biological: Amniotic Suspension Allograft<br>* This investigational product is a cryopreserved product derived from human amnion and cells from the amniotic fluid.<br>|
| Placebo Comparator: Placebo<br>Participants receive a single IA injection of 4 mL of normal saline | Drug: Placebo<br>* Matching placebo is 0.9% normal saline: 4 mL to be injected IA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in change from baseline in WOMAC Pain scale at 6 months between ASA- and placebo-treated patients | The WOMAC is widely used in the evaluation of hip and knee OA. It is a self-administered questionnaire consisting of 24 items divided into 3 subscales: pain, stiffness, and physical function. The WOMAC measure has been used in clinical trials to evaluate the efficacy of surgical treatments, medicinal and biological products, devices, and physical therapies. | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference between changes from baseline for ASA- and placebo- treated patients in WOMAC Function at 6 months | The WOMAC is widely used in the evaluation of hip and knee OA. It is a self-administered questionnaire consisting of 24 items divided into 3 subscales: pain, stiffness, and physical function. The WOMAC measure has been used in clinical trials to evaluate the efficacy of surgical treatments, medicinal and biological products, devices, and physical therapies. | Baseline to Week 26 | 
| The difference between changes from baseline for ASA- and placebo-treated patients in the OMERACT-OARSI responder rate at 6 months | The OMERACT-OARSI core domain set for clinical trials in hip and/or knee osteoarthritis responder criteria will be used to assess whether a patient is a responder or not. | Baseline to Week 26 | 
| The difference between changes from baseline for ASA- and placebo-treated patients in WOMAC Pain at 3 months | The WOMAC is widely used in the evaluation of hip and knee OA. It is a self-administered questionnaire consisting of 24 items divided into 3 subscales: pain, stiffness, and physical function. The WOMAC measure has been used in clinical trials to evaluate the efficacy of surgical treatments, medicinal and biological products, devices, and physical therapies. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Knee, Arthritis, Joint Disease, Musculoskeletal Diseases, Rheumatic Diseases