A Study of the Safety and Efficacy of Subcutaneously Administered REGN475 in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This is a double-blind, prospective, randomized study in which patients will be randomized to 1 of 5 treatment arms (4 active and 1 placebo). Each patient will receive one SC injection of REGN475 or placebo and 1 IV infusion of either REGN475 or placebo, on day 1 (baseline) In order to preserve the blind, patients receiving REGN475 SC will also receive placebo IV, and patients receiving REGN475 IV will also receive placebo SC.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Parallel Group, Single Dose Study of the Safety and Efficacy of Subcutaneously Administered REGN475 in Patients With Osteoarthritis of the Knee

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: REGN475
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of OA of the knee according to American College of Rheumatology (ACR) criteria, and experiencing moderate to severe pain in the index knee for at least 3 months prior to the screening visit. Kellgren-Lawrence grade 2-3 radiographic severity of the index knee at or within 6 months prior to Screening. Exclusion Criteria: Significant concomitant illness including, but not limited to, cardiac, renal, neurological, endocrinological, metabolic or lymphatic disease that would adversely affect the patient's participation in the study. Patients with joint replacement in the affected knee. Intra-articular injection of corticosteroids or hyaluronic acid in the affected knee within the 3 months prior to the screening visit. Women who are pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>SC REGN475 Dose 1 and IV Placebo | Biological: REGN475<br> <br> |
| Experimental: Dose 2<br>SC REGN475 Dose 2 and IV Placebo | Biological: REGN475<br> <br> |
| Experimental: Dose 3<br>SC REGN475 Dose 3 and IV Placebo | Biological: REGN475<br> <br> |
| Experimental: Dose 4<br>SC Placebo and IV REGN475 Dose 4 | Biological: REGN475<br> <br> |
| Placebo Comparator: Dose 5<br>SC Placebo and IV Placebo | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment-emergent adverse events (TEAEs) in patients treated with REGN475 or placebo. |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-integrated change from baseline in walking knee pain using the Numeric Rating Scale (NRS). |  | 8 weeks | 
| Change from baseline in walking knee pain using the Numeric Rating Scale (NRS). |  | 8 weeks | 
| Time-integrated change from baseline in The Western Ontario and McMaster Osteoarthritis Index (WOMAC) |  | 8 weeks | 
| Change from baseline in The Western Ontario and McMaster Osteoarthritis Index (WOMAC) |  | 8 weeks | 
| Patient assessment of response to treatment over time using the Patient Global Impression of Change. |  | 16 weeks | 
| Change from baseline in patient-rated QOL using the Short-Form 12-Item Questionnaire (SF-12). |  | 8 weeks |