An Efficacy and Safety Study of Two Doses of Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This study will evaluate the efficacy of two doses of Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee.

Detailed Description
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A Randomized, Placebo-controlled, Double-Blind Study to Evaluate the Efficacy and Safety of two Doses of Intra-Articular Injection of Ampion™ in Adults with pain due to osteoarthritis of the knee. The primary trial objective is to evaluate whether there is greater efficacy of 10 mL Ampion™ versus 10 mL placebo than 4 mL Ampion™ versus 4 mL placebo intra-articular (IA) injection in improving knee pain, when applied to patients suffering from OA of the knee. The secondary trial objective include: the evaluation of the safety of an intra-articular injection of Ampion™ when applied to patients suffering from OA of the knee, evaluation of the efficacy of intra-articular injection of Ampion™ and placebo on stiffness and function when applied to patients suffering from OA of the knee and evaluation of responder status defined by the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) Criteria.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy and Safety of Two Doses of Intra-Articular Injection of Ampion™ in Adults With Pain Due to Osteoarthritis of the Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Biological: 4 mL injection of Ampion
* Biological: 10 mL Injection of Ampion
* Drug: 4 mL Injection of Placebo
* Drug: 10 mL Injection of Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent to participate in the study Willing and able to comply with all study requirements and instructions of the site study staff Male or female, 40 years to 85 years old (inclusive) Must be ambulatory Index knee must be symptomatic for greater than 6 months with a clinical diagnosis of osteoarthritis (OA) and supported by radiological evidence Kellgren Lawrence Grade II to IV) that is not older than 6 months prior to the date of screening Moderate to moderately-severe OA pain in the index knee (rating of at least 1.5 on the WOMAC Index 3.1 5-point Likert Pain Subscale) assessed at screening Moderate to moderately-severe OA pain in the index knee (even if chronic doses of nonsteroidal anti-inflammatory drug (NSAID), which have not changed in the 4 weeks prior to screening, have been/are being used) No analgesia (including acetaminophen [paracetamol]) taken 12 hours prior to an efficacy measure No known clinically significant liver abnormality e.g. cirrhosis, transplant, etc.) Exclusion Criteria: As a result of medical review and screening investigation, the Principal Investigator considers the patient unfit for the study A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion) A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate) Presence of tense effusions Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee, as assessed locally by the Principal Investigator Isolated patella femoral syndrome, also known as chondromalacia Any other disease or condition interfering with the free use and evaluation of the index knee for the duration of the trial e.g. cancer, congenital defects, spine OA) Major injury to the index knee within the 12 months prior to screening Severe hip OA ipsilateral to the index knee Any pain that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee) Any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study Use of the following medications: No IA injected pain medications in the study knee during the study No analgesics containing opioids. NSAIDs may be continued at levels preceding the study and acetaminophen is available as a rescue medication during the study from the provided supply No topical treatment on osteoarthritis index knee during the study No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as Aspirin and Plavix are allowed) No systemic treatments that may interfere with safety or efficacy assessments during the study No immunosuppressants No use of corticosteroids > 10 mg prednisolone equivalent per day (if ≤ 10 mg prednisolone, the dose must be stable) Any human albumin treatment in the 3 months before randomization

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: Ampion 4 mL Dose<br>4 mL Injection of Ampion | Biological: 4 mL injection of Ampion<br>* 4 mL Injection of Ampion<br>|
| Placebo Comparator: Placebo 4 mL Dose<br>4 mL Injection of Placebo | Drug: 4 mL Injection of Placebo<br>* 4 mL Injection of Placebo<br>* Other names: Saline;|
| Experimental: Ampion 10 mL Dose<br>10 mL Injection of Ampion | Biological: 10 mL Injection of Ampion<br>* 10 mL Injection of Ampion<br>|
| Placebo Comparator: Placebo 10 mL Dose<br>10 mL Injection of Placebo | Drug: 10 mL Injection of Placebo<br>* 10 mL Injection of Placebo<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Pain | Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain. | Scored at Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Function | Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function. | Scored at Baseline and 12 weeks. | 
| Change in Knee Stiffness. | Mean Change in WOMAC B stiffness score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a reduction in stiffness. | Scored at Baseline and 12 weeks. | 
| Change in Patient's Global Assessment | Patients are asked the following question: Considering all the ways in which your arthritis affects you, please indicate how you are doing. 5-point Likert scale (0 = very well, 1 = well, 2 = fair, 3 = poor, 4 = very poor). A negative value constitutes an improvement in patient's assessment of disease severity. | Scored at Baseline and 12 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, osteoarthritis of the knee