Safety Study of a Long-Acting Injectable Steroid to Treat Knee Osteoarthritis

Study Overview
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Brief Summary
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The main purpose of this study is to understand the pharmacokinetics of EP-104IAR and to determine whether it is safe to use in patients with osteoarthritis (OA) of the knee. The study will also provide some preliminary insights into whether the experimental treatment reduces pain in the knee. Osteoarthritis is the most common joint disease, affecting over 20 million people in the US alone. Currently, pain treatments that are injected directly into the knee often work for only a short time and may also have side effects within the rest of the body. The experimental treatment is a steroid that is in the same family of drugs as the most common current injectable treatments for knee osteoarthritis. For this study, the drug is coated with a polymer intended to prolong the time it stays inside the knee and lessen potential side effects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial Evaluating the Pharmacokinetics, Safety and Preliminary Efficacy of EP-104IAR (Long-Acting Fluticasone Propionate) in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: EP-104IAR
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OA of Index Knee Kellgren Lawrence Grade 2 or 3 Patient-reported pain (PtPain) of Index Knee ≥4 but ≤9 PtPain of non-Index Knee <6 BMI ≦ 40 kg/m2 Exclusion Criteria: Intra-articular joint injection in the Index Knee within the past 8 weeks for glucocorticoids and 6 months for hyaluronic acid Insulin-dependent diabetes Active infection Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 40 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: EP-104IAR<br>15mg EP-104IAR in 4 mL carrier fluid | Drug: EP-104IAR<br>* Single, ultrasound-guided injection of EP-104IAR into the knee<br>|
| Placebo Comparator: Vehicle<br>4 mL carrier fluid | Drug: Vehicle<br>* Single, ultrasound-guided injection of vehicle placebo into the knee<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of fluticasone propionate |  | Up to 42 weeks | 
| Fluticasone propionate concentrations in synovial fluid |  | Up to 30 weeks | 
| Area under the plasma concentration versus time curve (AUC) of fluticasone propionate |  | 12 weeks | 
| Incidence of treatment-emergent adverse events |  | Up to 42 weeks | 
| Change from baseline in clinical laboratory parameters: hematology, chemistry (including cortisol) and urinalysis |  | Up to 42 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to baseline pain in patient-reported Pain Numerical Rating Scale for Index knee |  | Weekly up to 42 weeks | 
| Change from baseline in patient-reported Pain Numerical Rating Scale for Index knee |  | Weekly up to 42 weeks | 
| Change from baseline in patient-reported Global Assessment of Arthritis |  | Up to 42 weeks | 
| Change from baseline in patient-reported Western Ontario and McMaster Universities Arthritis Index (WOMAC) |  | Up to 42 weeks | 
| Change from baseline in patient-reported Short Form - 36 quality of life scores |  | Up to 42 weeks | 
| Change from baseline in Physician's Global Assessment of Arthritis |  | Up to 42 weeks | 

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