Trial Comparing Three Single Dose Injections for Knee Osteoarthritis

Study Overview
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Brief Summary
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This study is a 3-arm, double-blind, randomized trial comparing the clinical outcomes of Zilretta, Synvisc One, and Monovisc for knee OA.

Detailed Description
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Knee osteoarthritis (OA) is a leading cause of disability worldwide.1,2 Standard of care treatments for knee OA include activity modification, weight loss, therapeutic exercise and medications like non-steroidal anti-inflammatory drugs (NSAIDs). If these measures fail, injections like corticosteroids and hyaluronate (HA) can be helpful for pain control.3 The aforementioned injections have unique mechanisms of action. Steroid injections work through reducing joint inflammation, while HA works by lubricating and cushioning the joint. There are several varieties of steroids and HA injections that have been approved by the Food and Drug Administration for use in knee OA. Among these variations are extended-release triamcinolone (Zilretta), hylan GF-20 (synvisc one), and hyaluronan (monovisc). While each are FDA approved and commonly used in orthopedic and sports medicine clinics, they have never been directly compared in any study. Therefore, when selecting a treatment for a patient, it is largely based on provider preference, not clinical data. This study is a 3-arm, double-blind, randomized trial comparing the clinical outcomes of Zilretta, Synvisc One, and Monovisc for knee OA.

Official Title
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A Double-blind, Randomized Trial Comparing Three Single Dose Injections for Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Zilretta
* Drug: Synvisc-One 48 MG in 6 ML Prefilled Syringe
* Drug: Monovisc 88 MG Per 4 ML Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-85 years BMI < 40 Diagnosis of unilateral knee OA Radiographic evidence of OA of the target knee (Kellgren-Lawrence grades 2-4) Continued OA pain in the target knee despite at least 6 weeks of: physical therapy and at least one of the following: activity modification (such as reducing impact on the knee), weight loss, and a 2 week trial of NSAID / acetaminophen. Knee Osteoarthritis Outcomes Score (KOOS)-Pain subscale 20-65 Working knowledge of English language (to be able to complete all outcome scores) Ability to attend all follow-up appointments Exclusion Criteria: 3+ effusion of the target knee (stroke test grading system) Prior injection therapy: Steroid injection in target knee in the last 3 months Viscosupplementation in target knee in the last 6 months PRP in the target knee in the last 6 months Cellular treatments in index knee (bone marrow, amniotic suspensions etc) 1 year Participation in any experimental device or drug study within 1 year before screening visit Oral or IM steroids in the last 3 months (Inhaled steroids used in the treatment of asthma/allergies are permitted) Medical condition that may impact outcomes of procedure including: Systemic inflammatory disorders that impact the joints like rheumatoid arthritis, lupus, etc Undergoing current cancer treatment (other than non-melanoma skin malignancies) Taking immunosuppressants Previous cartilage repair procedure on the injured cartilage surface (ie, OATS, ACI, MFX) in the last 5 years Previous surgery at the target knee within the past 1 year Any degree of cognitive impairment Symptomatic OA of any other joint in the lower limbs Pregnancy, lactating, or intent to become pregnant during treatment period (Female participants will be asked if they are pregnant, lactating, or intend to become pregnant during treatment) Gout, Pseudogout (including radiographic evidence of chondrocalcinosis) History of infection or current infection at the affected joint Smoking (Former smokers< 1 year from quit date)

Ages Eligible for Study
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Minimum Age: 25 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 |
| --- | --- |
| Active Comparator: Zilretta<br>Generic Name: Triamcinolone acetonide Zilretta is an extended-release synthetic corticosteroid indicated as an intra-articular injection for the management ofosteoarthritis pain of the knee. 5mL suspension of 32 mg of triamsinolone administered as a 1 dose parapatellar intra-articular injection. | Drug: Zilretta<br>* Intra-articular injection to treat knee osteoarthritis<br>|
| Active Comparator: Synvisc One<br>Generic Name: Hylan G-F 20 Synvisc-One combines the three doses of SYNVISC (hylan G-F 20) which consists of hylan A (average molecular weight6,000,000 daltons) and hylan B hydrated gel in a buffered physiological sodium chloride solution, pH 7.2. Each 10 mL syringe of Synvisc-One combines the three 2-mL doses (16 mg each) of a complete SYNVISC treatment regimen (48 mg). Synvisc-One belongs to a class of drugs called Intra-Articular Agents; Rheumatologics, Other. 10mL of Hylan G-F 20 administered as a 1 dose parapatellar intra-articular injection. | Drug: Synvisc-One 48 MG in 6 ML Prefilled Syringe<br>* Intra-articular injection to treat knee osteoarthritis<br>|
| Active Comparator: Monovisc<br>Generic Name: Hyaluronan The Monovisc™ device is a proprietary high molecular weight hyaluronic acid (HA) viscosupplementation intended for the treatment of pain in patients with moderate osteoarthritis (OA) of the knee who have failed conservative non-pharmacological therapy and simple analgesics. The device is administered by a single injection via the para-patellar approach under sterile conditions. 4mL injection of Hyaluronan administered as a 1 dose parapatellar intra-articular injection. | Drug: Monovisc 88 MG Per 4 ML Prefilled Syringe<br>* Intra-articular injection to treat knee osteoarthritis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee injury and Osteoarthritis Outcome Score (KOOS) Pain patient reported outcome questionnaire | KOOS Pain evaluates short-term and long-term pain in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee pain. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms patient reported outcome | KOOS symptoms evaluates short-term and long-term symptoms in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee symptoms. | Baseline, 3 month, 6 month | 
| Knee injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) patient reported outcome | KOOS ADL evaluates short-term and long-term function in daily living in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to daily living activity. | Baseline, 3 month, 6 month | 
| Knee injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation (Sport/Rec) patient reported outcome | KOOS Sport/Rec evaluates short-term and long-term function in sports and recreation in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to sports or recreation activity. | Baseline, 3 month, 6 month | 
| Knee injury and Osteoarthritis Outcome Score (KOOS) knee related quality of life (QOL) patient reported outcome | KOOS QOL evaluates short-term and long-term knee quality of life in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee related issues in regards to quality of life. | Baseline, 3 month, 6 month | 
| Knee injury and Osteoarthritis Outcome Score (KOOS) Pain patient reported outcome | KOOS Pain evaluates short-term and long-term pain in subjects with knee injury and osteoarthritis. Scores range from 0-100 where 100 represents no knee pain. | Baseline, 3 month |