A Study to Evaluate Safety of Three Intra-articular Injections of Ampion in the Knee of Adults With Osteoarthritis Pain

Study Overview
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Brief Summary
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Phase 1 will evaluate the safety of 3 intra-articular injections of Ampion™ administered 2 weeks apart to adults with osteoarthritis of the knee. In the absence of serious drug-related Adverse Events (AEs) of unanticipated drug-related AEs, enrollment will be initiated in Phase 2 of the study. Phase 2 will evaluate the efficacy of 3 intra-articular injections, given 2 weeks apart, of Ampion™ in Adults with pain due to osteoarthritis of the knee.

Detailed Description
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Phase 1: An open-label study to evaluate the safety of 3 intra-articular injections of of Ampion™ 4 mL at Baseline (Day 0) and Weeks 2 and 4 to adults with osteoarthritis (OA) knee pain. Enrollment will be initiated in Phase 2 if no serious drug-related adverse events or unanticipated drug-related adverse events are observed. Phase 2: A randomized, placebo-controlled, double-blind, study to evaluate the safety and efficacy of 3 intra-articular (IA) injections of Ampion™ 4 mL at Baseline (Day 0) and Weeks 2 and 4 in adults with OA knee pain. Study Objectives Phase 1: To evaluate the safety of Ampion™ 4 mL administered as 3 intra-articular injections, two weeks apart, in subjects suffering from OA of the knee from Baseline to Week 20. Phase 2: The primary study objective is to evaluate the safety and efficacy of Ampion™ 4 mL versus placebo injection from Baseline to Week 20, when administered as three intra-articular (IA) injections (at Baseline (Day 0) and Weeks 2 and 4), in improving knee pain in subjects suffering from OA of the knee.

Official Title
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A Prospective Phase 1/2 Study to Evaluate the Safety and Exploratory Efficacy of Three Intra-articular Injections of Ampion™ (4 mL) Administered Two Weeks Apart 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
* Drug: 4 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) Ambulatory Index knee must have been symptomatic for greater than 6 months with a clinical diagnosis of OA and supported by radiological evidence (Kellgren Lawrence Grade II-IV) acquired at Screening Moderate to moderately severe OA pain in the index knee (rating of at least 1.5 on the WOMAC Pain Subscale) assessed at Screening and confirmed at randomization Moderate to moderately severe OA pain in the index knee (even if chronic doses of nonsteroidal anti-inflammatory drugs [NSAIDs], which have not changed in the 4 weeks prior to Screening, had been used) No analgesia taken 24 hours before efficacy measure Exclusion Criteria: As a result of medical review and screening investigation, the Principal Investigator considered the subject unfit for the study Previous Ampion injection Known clinically significant liver abnormality (eg, cirrhosis, transplant, etc.) History of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin was not an exclusion criterion) History of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate) Presence of tense effusions in the index knee Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the index knee, as assessed locally by the Principal Investigator Isolated patella femoral syndrome, also known as chondromalacia in the index knee Any other disease or condition interfering with the free use and evaluation of the index knee for the duration of the trial (eg, 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 (eg, 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 treatment or likely to be changed during the duration of the study Use of any of the following medications: IA-injected pain medications in the index knee during the study Analgesics containing opioids (NSAIDs were allowed at the levels preceding the study and acetaminophen was available as rescue medication during the study from the provided supply) Topical prescription treatment on the index knee during the study Significant anticoagulant therapy (eg, heparin or enoxaparin) during the study (aspirin and clopidogrel were allowed) Systemic treatments that could interfere with safety or efficacy assessments during the study Immunosuppressants Corticosteroids >10 mg prednisolone equivalent per day or corticosteroids at doses ≤10 mg prednisolone equivalent that had been changed during the study 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> <br> * Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events and Serious Adverse Events (Phase 1) | Incidence and severity of adverse events and serious adverse events evaluated at 24 weeks | 24 Weeks | 
| Change in Knee Pain (Phase 2) | 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 20 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Knee Function (Phase 2) | 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 20 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