Cingal Study for Knee Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this study is to see if a single injection of Cingal into the knee provides safe relief of pain caused by osteoarthritis.

Detailed Description
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This study compared three groups of subjects. Group One received a single injection of Cingal (Hyaluronic Acid plus Triamcinolone Hexacetonide). Group Two received a single injection of Monovisc (Hyaluronic Acid). Group Three received a single injection of saline as a placebo.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Multi-Center Study of a Single Injection Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Hyaluronic Acid and TH (Cingal®)
* Device: Hyaluronic Acid (Monovisc®)
* Device: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is 40 - 75 years old with a Body Mass Index (BMI)≤ 40 kg/m2 Subject has Kellgren-Lawrence (K-L) severity grade I, II, or III in the index knee as determined by X-Ray. Contralateral knee: K-L severity grade 0, I, or II. Exclusion Criteria: Subject received an intra-articular (IA) injection of Hyaluronic Acid (HA) and/or steroid in either knee within 6 months of signing the informed consent form (ICF). Subject had an arthroscopy of either knee within 3 months of signing the informed consent form (ICF).

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Single injection of 0.9% saline supplied as a 4 milliliter (mL) unit dose in a 5mL glass syringe | Device: Saline<br>* Saline placebo packaged to look identical to comparator syringes. Injection into knee.<br>|
| Experimental: Hyaluronic Acid and TH (Cingal®)<br>Single injection of sodium hyaluronate with triamcinolone hexacetonide (TH) supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe | Device: Hyaluronic Acid and TH (Cingal®)<br>* Injection into knee<br>* Other names: Cingal®;|
| Active Comparator: Hyaluronic Acid (Monovisc®)<br>Single injection of sodium hyaluronate supplied as a 4 milliliter (mL) unit dose in a 5 mL glass syringe | Device: Hyaluronic Acid (Monovisc®)<br>* Injection into knee<br>* Other names: Monovisc®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT) | The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 12 Weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (PP) | The change in knee pain from baseline to 12 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT) | The change in knee pain from baseline to 1 week post treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 1 Week | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT) | The change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (ITT population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the change from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 3 Weeks | 
| OMERACT-OARSI Responder Index Comparing Cingal® to Saline (ITT) | The post treatment Responder Rate at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome. | 12 Weeks | 
| Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT) | The change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 mm = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 12 Weeks | 
| Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT) | The change from baseline to 1 week in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 1 Week | 
| Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT) | Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (ITT population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 3 Weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT) | Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group. The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 26 Weeks | 
| Evaluator Global Assessment Comparing Cingal® to Saline (ITT) | Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 12 Weeks | 
| Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT) | Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 1 Week | 
| Evaluator Global Assessment Comparing Cingal® to Monovisc® (ITT) | Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 3 Week | 
| Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT) | Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (ITT population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 26 Weeks | 
| Evaluator Global Assessment Comparing Cingal® to Saline (ITT) | Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (ITT population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 26 Weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP) | Mean change in knee pain from baseline to 1 week as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 1 Week | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (PP) | Mean change in knee pain from baseline to 3 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Monovisc® group (PP population). The WOMAC Pain Score is a validated visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 3 Weeks | 
| OMERACT-OARSI Responder Index Comparing Cingal® to Saline (PP) | The post treatment Responder Rate comparing Cingal® and Saline at 12 weeks is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. The criteria for response are (1) improvement in pain or physical function ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. A higher percentage of subjects responding indicates a better outcome. | 12 Weeks | 
| Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP) | Mean change from baseline to 12 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 12 Weeks | 
| Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP) | The post treatment Responder Rate comparing Cingal® and Monovisc® at 1 week is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index (PP population). The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder. A higher percentage of subjects responding indicates a better outcome. | 1 Week | 
| Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (PP) | Mean change from baseline to 3 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Monovisc® arms (PP population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 3 Weeks | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline. (PP) | Mean change in knee pain from baseline to 26 weeks as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal® group to the Saline group (PP population). The WOMAC Pain Score is a validated 100mm visual analog scale from 0 mm = no pain to 100 mm = highest pain level. A negative number for the difference from baseline indicates reduction in pain. A greater negative difference from baseline means a better outcome. | 26 Weeks | 
| Evaluator Global Assessment Comparing Cingal® to Saline (PP) | Mean change from baseline to 12 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 12 Weeks | 
| Evaluator Global Assessment Comparing Cingal® and Monovisc® (PP). | Mean change from baseline to 1 week in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 1 Week | 
| Evaluator Global Assessment Comparing Cingal® to Monovisc® (PP) | Mean change from baseline to 3 weeks in the Evaluator Global Assessment comparing the Cingal® and Monovisc® arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 3 Week | 
| Patient Global Assessment (PGA) Comparing Cingal® to Saline (PP) | Mean change from baseline to 26 weeks in the Patient Global Assessment (PGA) comparing the Cingal® and Saline arms (PP population). The PGA is completed by the subject answering the question Considering all the ways the osteoarthritis in your STUDY knee affects you, what is your assessment of how much your STUDY knee is bothering you today? The PGA is scored on a 100mm visual analog scale, where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates an improvement in the patient assessment. A greater negative difference means a better outcome. | 26 Weeks | 
| Evaluator Global Assessment Comparing Cingal® to Saline (PP) | Mean change from baseline to 26 weeks in the Evaluator Global Assessment comparing the Cingal® and Saline arms (PP population). The Evaluator Global Assessment is completed by the Outcomes Assessor, and answers the question Considering all the ways the osteoarthritis in the patient's index knee bothers him/her, what is your assessment of how much the patient's knee is bothering him/her today? The Evaluator Global Assessment is scored on a visual analog scale where 0 = the patient is not bothered, to 100 mm = the patient is bothered to the highest degree. A negative number for the difference from baseline indicates improvement in the assessment. A greater negative difference means a better outcome. | 26 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee osteoarthritis, Hyaluronic acid, HA Injection, Steroid Injection, Knee injection