Study to Evaluate the Efficacy and Safety of EP-104IAR in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, efficacy and pharmacokinetics (PK) of EP-104IAR in patients with osteoarthritis (OA) of the knee

Detailed Description
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This is a randomized, double-blind, placebo-controlled, single injection, 24-week study to evaluate the safety, efficacy and PK of EP-104IAR in subjects with osteoarthritis knee pain Following screening and baseline assessments to determine eligibility, each participant will receive a single IA injection of either EP-104IAR or placebo (vehicle). Participants will be followed up for 24 weeks following the injection for safety, PK and efficacy assessments.

Official Title
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A Phase 2, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety, Efficacy and Pharmacokinetics of Single Dose EP-104IAR for 24 Weeks in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: EP-104IAR 25 mg
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or females, aged ≥40 years Body Mass Index (BMI) ≤ 40.0 kg/m2 Diagnosis of primary OA of the Index knee, with symptoms present for at least 6 months OA severity Grade 2 or 3 (based on Kellgren Lawrence Grading Scale) Unsatisfactory pain relief from at least 2 prior standard OA treatments Qualifying pain in the Index knee during the baseline period Ambulatory (without the need for a cane/other walking aide) Female subjects willing to use highly effective birth control methods to prevent pregnancy Willing and able to comply with study procedures and restrictions, including abstaining from use of restricted medications. Key Exclusion Criteria: OA of the Index knee due to acute injury or trauma, or unstable joint X-ray evidence of chondrocalcinosis Diagnosed or suspected ipsilateral hip OA Knee pain that is not attributable to OA of the knee Any other disorders that impact mobility, strength or sensation, or are a co-existent source of pain or inflammation that interfere with assessment of knee pain and function History of infection in the Index knee Skin breakdown on the Index knee where the injection will take place Total Knee Replacement, or any other surgery (including arthroscopy) for the Index knee within prior 12 months, or planned surgery during the study Total Knee Replacement Surgery of the non-Index knee within prior 6 months, or planned surgery (any location) during the study that would require a restricted medication IA injection of corticosteroids in any joint within prior 3 months or IA injection of extended-release corticosteroids in any joint within prior 6 months IA injection in the Index knee of platelet rich plasma, or other prolotherapy within prior 3 months, or hyaluronic acid within prior 6 months Recent, current or planned use of corticosteroids for any indication (except for permitted uses) Recent, current or planned use of prohibited medications (including analgesics, marijuana, investigational drugs and devices, immunosuppressive therapy), or unwilling or unable to stop using prohibited medications during the study. Conditions including: sarcoidosis, amyloidosis, osteomyelitis, Cushing's Syndrome, hepatic or renal disease, Psychotic disorder, bipolar disorder, symptomatic depressive or anxiety disorders. Current malignancy of any type, or history of a malignancy within prior 12 months Active or quiescent systemic fungal, bacterial (including tuberculosis) viral (including HIV, Hepatitis B or C) or parasitic infections, or ocular herpes simplex, or any recent infection requiring IV or oral antibiotics Laboratory results indicative of adrenal insufficiency, diabetes or renal or hepatic disease. Positive urine drug screen for a substance of abuse Females who are pregnant, lactating Known or suspected hypersensitivity or contraindication to ingredients in the study drug

Ages Eligible for Study
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Minimum Age: 40 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: Subjects will be randomized to received either EP-104IAR or placebo (vehicle) in a parallel group fashion.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EP-104IAR 25 mg<br>A single use intra-articular injection containing 25 mg of EP-104IAR | Drug: EP-104IAR 25 mg<br>* Single 5 mL intra-articular injection<br>|
| Placebo Comparator: Placebo (vehicle)<br>A single use intra-articular injection containing no active ingredients | Drug: Vehicle<br>* Single 5 mL intra-articular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in change from baseline between EP-104IAR and vehicle in WOMAC Pain subscale | WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Pain subscale includes 5 questions related to the pain of osteoarthritis (score range 0-20). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in change from baseline between EP-104IAR and vehicle in WOMAC Function subscale | WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Function subscale includes 17 questions related to the physical functioning of osteoarthritis e.g. stair use, standing, walking etc. (score range 0-68) | 12 weeks | 
| Difference between EP-104IAR and vehicle in the area under the curve (AUC) of WOMAC Pain subscale | WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Pain subscale includes 5 questions related to the pain of osteoarthritis (score range 0-20). | 12 weeks | 
| Difference in change from baseline between EP-104IAR and vehicle in WOMAC Pain subscale | WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. Pain subscale includes 5 questions related to the pain of osteoarthritis (score range 0-20). | 24 weeks | 
| Difference between EP-104IAR and vehicle in OMERACT-OARSI strict responders | OMERACT-OARSI = Outcome Measures in Rheumatology-Osteoarthritis Research Society International | 12 weeks |