Cingal Study for Knee Osteoarthritis

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.