Osteoarthritis, Knee
Conditions
Keywords
osteoarthritis, knee
Brief summary
This multicenter, randomized, double-blind study will be performed in approximately 600 subjects with chronic idiopathic osteoarthritis (OA) of the knee. An open-label safety extension will follow.
Interventions
DEVICEEUFLEXXA™
EUFLEXXA™ is supplied in a single-dose syringe containing 20 mg/2 ml of 1% sodium hyaluronate (molecular weight 2.4-3.6 MD); sodium chloride, 17 mg; disodium hydrogen phosphate dodecahydrate, 1.12 mg; sodium dihydrogen phosphate dihydrate, 0.1 mg; enough water for injection to make 2.0 ml. EUFLEXXA™ is supplied in 2.25 ml nominal volume, disposable prefilled glass syringes containing 2 mL of EUFLEXXA™. Only the contents of the syringe are sterile. EUFLEXXA™ is nonpyrogenic. See package insert for further details.
DEVICEplacebo
Placebo is supplied in a disposable prefilled glass syringe. Each single-dose syringe will contain 2 mL of phosphate buffered saline. Only the contents of the syringe are sterile.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Chronic OA of target knee confirmed by ACR Criteria 2. Pain due to OA in target knee present for at least 6 months: • Moderate to severe pain score of 41 mm to 90 mm recorded on a 100 mm VAS immediately following a 50-foot walk 3. A bilateral standing AP X-ray confirming OA of the target knee-obtained within a 6-month period prior to the Screening Visit-and a grade of 2 or 3 according to the Kellgren and Lawrence Grading Scale 4. Ability and willingness to use only acetaminophen as the analgesic (rescue) study medication * The acetaminophen dose must not exceed 4 grams/day (4000 mg) * If subject has known chronic liver disease, the maximum dose of acetaminophen must not exceed 2 grams/day (2000 mg) * The subject must be willing and able to discontinue acetaminophen at least 24 hours prior to all study-specific visits * The study specific acetaminophen provided will only be used for knee pain. 5. Ability to perform procedures required of the pain index evaluations (unassisted walking 50 feet on a flat surface and going up and down stairs). 6. Willingness and ability to complete efficacy and safety questionnaires and ability to read and understand study instructions 7. Signed study-specific Subject Informed Consent Form
Exclusion criteria
1. Any major injury (including sports injuries) to the target knee within the 12 months prior to the Screening Visit 2. Any surgery to the target knee within the 12 months prior to the Screening Visit, or surgery to the contralateral knee or other weight-bearing joint if it will interfere with knee assessments 3. Prior articular procedures, such as transplants or ligament reconstruction to the target knee 4. Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis 5. Gout or calcium pyrophosphate (pseudogout) diseases that have flared within the previous 6 months prior to the Screening Visit 6. X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee 7. Osteonecrosis of either knee 8. Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication 9. Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee 10. Significant target knee joint infection or skin disorder/infection within the previous 6 months prior to study enrollment 11. Symptomatic OA of the hips, spine, or ankle, if it would interfere with the evaluation of the target knee 12. Known hypersensitivity to acetaminophen, EUFLEXXA™, or Phosphate buffered saline solution 13. Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the entire study period 14. Recurrent medical history of severe allergic or immune-mediated reactions or other immune disorders 15. Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation 16. Current treatment or treatment within the previous 2 years prior to the Screening Visit for any malignancy unless specific written permission is provided by the Sponsor (excluding basal cell or squamous cell carcinoma of the skin) 17. Active liver disease based on liver profile of AST, ALT, and conjugated bilirubin \>2 times the upper limit of normal 18. Renal insufficiency based on serum creatinine \>2.0 mg/dL 19. Any clinically significant laboratory value based on clinical history that the Investigator feels may affect the study evaluation 20. Any intercurrent chronic disease or condition that may interfere with the completion of the 6-month (or 12-month) follow-up of the study, such as liver disease, severe coronary disease, drug abuse, disordered mental state, or other clinically significant condition 21. Current alcoholism, and/or any known current addiction to pain medications 22. Any clinically significant finding that would place the patient at health risk, impact the study, or affect the completion of the study 23. Any psychiatric illness that would prevent comprehension of the details and nature of the study 24. Participation in any experimental drug or device study within the 6 months prior to the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Weeks 0, 26 | The level of pain is estimated by the participant following a walk of 50 feet in length which is observed by the investigator. Pain estimates were evaluated on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed. |
| Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Weeks 0 and 26 | The percent difference in participant pain recorded by the participant during a walk of 50 feet in length between the baseline (week 0) and week 26 scores. Scores are measured on a visual analog scale of 100 millimeters; a score of 0 millimeters meaning no pain was observed; a score of 100 millimeters meaning extreme pain was observed. |
| Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | weeks 26 and 52 | Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Range of motion indicates the flexibility of the knee, and is measured by the number of degrees between when the knee is hyper-extended and when the knee is flexed. |
| Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | weeks 26 and 52 | Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Tenderness of the knee was subjectively rated by participants as none, mild, moderate or severe. |
| Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52 | weeks 26 and 52 | Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Local warmth of the target knee was recorded as Yes (warmth present) or No (knee was not warmer than expected). |
| Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52 | weeks 26 and 52 | Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Redness of the knee was subjectively rated as Yes (knee was red) and No (knee was not red). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient Global Assessment of Knee Pain at Week 26 | Weeks 0 and 26 | Participant assessment of knee pain evaluated on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain; a score of 100 millimeters means extreme pain. |
| Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26. | Weeks 0 and 26 | The change in the number of tablets of 500 milligram acetaminophen used in a week as rescue medication is compared at weeks 0 and weeks 26. |
| Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26 | Weeks 0, 26 | The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' physical function. The questionnaire is completed by participants. |
| Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26 | weeks 0 and 26 | The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' bodily pain scores. The questionnaire is completed by participants. |
| Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26 | weeks 0 and 26 | The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' general health scores. The questionnaire is completed by participants. |
| Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | weeks -1 and 26 | The percent difference in participant pain recorded by the participant during a walk of 50 feet in length between the screening (week -1) and week 26 scores. Scores are measured on a visual analog scale of 100 millimeters; a score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed. |
| Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test | Weeks 0 and 26 | Yes represents the number of participants whose pain during a walk of 50 feet in length was improved at week 26 over baseline by at least 20 millimeters. Pain was evaluated on a 100 millimeter visual analog scale by participants. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed. |
| Observed Pain Scores on the 50-foot Walk Test During the Extension Study | Baseline (week 26), week 52 | Participant pain during a walk of 50 feet in length was evaluated by participants on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed. |
| Mean Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Extension Study | Extension baseline (week 26), week 52 | The mean difference in participant pain as measured by participants during a walk of 50 feet in length between the baseline (week 26 pre-dose) and week 52 scores. Scores are measured on a visual analog scale of 100 millimeters, with a score of 0 millimeters meaning there was no pain observed; a score of 100 millimeters meaning extreme pain was observed. |
| Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52 | Week 52 (Extension Study) | Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer:YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter. |
| Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52. | Extension baseline (week 26 pre-dose), week 52 | The change in the number of tablets of study-specific acetaminophen taken per week as a rescue medication from knee pain. |
| Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26 | Weeks 0, 26 | The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. The questionnaire is completed by participants. This table summarizes the change from baseline in participants' physical health. |
| Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study for a Subpopulation of Participants With More Severe Knee Pain | weeks -1, 0, and 26 | Percent difference in participant pain during a walk of 50 feet in length between the mean screening (week -1) and baseline(week 0) scores, and week 26 scores. Scores are recorded by participants and measured on a visual analog scale of 100 millimeters, with 0 millimeters meaning there was no pain observed; 100 millimeters meaning extreme pain was observed. |
| Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12 | Week 12 | Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter. |
| Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26 | Week 26 | Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter. |
| Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12 | Week 12 | Responders are identified based on a calculation of three scales: WOMAC (A) pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter. |
| Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26 | week 26 | Responders are identified based on a calculation of three scales: WOMAC (A) pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter. |
Countries
United States
Participant flow
Pre-assignment details
A total of 821 patients were screened.
Participants by arm
| Arm | Count |
|---|---|
| EUFLEXXA™ Double-blind Each subject received 3 single-dose injections of EUFLEXXA™ (20 milligram/2 milliliter 1 percent sodium hyaluronate) into the target knee; one injection per week at weeks 0, 1 and 2. Patients were followed for 26 weeks following the first injection. | 293 |
| Placebo Double-blind Each subject received 3 single-dose injections of placebo into the target knee; one injection per week at weeks 0, 1 and 2. Patients were followed for 26 weeks following the first injection. | 295 |
| Total | 588 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind | Adverse Event | 11 | 6 | 0 |
| Double-blind | Data could not be retrieved | 2 | 2 | 0 |
| Double-blind | Lost to Follow-up | 4 | 3 | 0 |
| Double-blind | Other | 3 | 7 | 0 |
| Double-blind | Protocol Violation | 3 | 3 | 0 |
| Double-blind | Use of exclusionary medication | 1 | 2 | 0 |
| Double-blind | Withdrawal by Subject | 12 | 13 | 0 |
| Open-label Extension | Adverse Event | 0 | 0 | 13 |
| Open-label Extension | Lost to Follow-up | 0 | 0 | 12 |
| Open-label Extension | Other | 0 | 0 | 7 |
| Open-label Extension | Protocol Violation | 0 | 0 | 7 |
| Open-label Extension | Use of exclusionary medication | 0 | 0 | 3 |
| Open-label Extension | Withdrawal by Subject | 0 | 0 | 13 |
Baseline characteristics
| Characteristic | EUFLEXXA™ Double-blind | Placebo Double-blind | Total |
|---|---|---|---|
| Age Continuous | 62.5 years STANDARD_DEVIATION 10.62 | 60.8 years STANDARD_DEVIATION 10.31 | 61.6 years STANDARD_DEVIATION 10.5 |
| Body Mass Index (BMI) | 32.36 kilograms/meters square STANDARD_DEVIATION 7.446 | 33.03 kilograms/meters square STANDARD_DEVIATION 7.444 | 32.70 kilograms/meters square STANDARD_DEVIATION 7.446 |
| Race/Ethnicity, Customized African American | 26 participants | 33 participants | 59 participants |
| Race/Ethnicity, Customized Asian | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized Caucasian | 231 participants | 228 participants | 459 participants |
| Race/Ethnicity, Customized Hispanic | 29 participants | 25 participants | 54 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 participants | 4 participants | 6 participants |
| Region of Enrollment United States | 293 participants | 295 participants | 588 participants |
| Sex: Female, Male Female | 185 Participants | 186 Participants | 371 Participants |
| Sex: Female, Male Male | 108 Participants | 109 Participants | 217 Participants |
| Weight | 91.0 kilograms STANDARD_DEVIATION 21.95 | 92.8 kilograms STANDARD_DEVIATION 21.68 | 91.9 kilograms STANDARD_DEVIATION 21.81 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 27 / 293 | 35 / 295 | 43 / 433 |
| serious Total, serious adverse events | 10 / 293 | 9 / 295 | 12 / 433 |
Outcome results
Primary
Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
The level of pain is estimated by the participant following a walk of 50 feet in length which is observed by the investigator. Pain estimates were evaluated on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed.
Time frame: Weeks 0, 26
Population: Intent to treat (ITT) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EUFLEXXA™ Double-blind | Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Baseline (Week 0) (n=291,295) | 55.6 units on a scale | Standard Deviation 22.06 |
| EUFLEXXA™ Double-blind | Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Week 26 (n=251,259) | 30.0 units on a scale | Standard Deviation 26.06 |
| Placebo Double-blind | Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Baseline (Week 0) (n=291,295) | 54.7 units on a scale | Standard Deviation 21.81 |
| Placebo Double-blind | Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | Week 26 (n=251,259) | 36.1 units on a scale | Standard Deviation 28.55 |
Primary
Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
The percent difference in participant pain recorded by the participant during a walk of 50 feet in length between the baseline (week 0) and week 26 scores. Scores are measured on a visual analog scale of 100 millimeters; a score of 0 millimeters meaning no pain was observed; a score of 100 millimeters meaning extreme pain was observed.
Time frame: Weeks 0 and 26
Population: Intent to treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | -30.9 percent change from baseline value | Standard Deviation 117.2 |
| Placebo Double-blind | Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | -14.9 percent change from baseline value | Standard Deviation 114.87 |
p-value: 0.002ANCOVA
Primary
Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Range of motion indicates the flexibility of the knee, and is measured by the number of degrees between when the knee is hyper-extended and when the knee is flexed.
Time frame: weeks 26 and 52
Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | >135 degrees week 26 / >135 degrees week 52 | 76 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 90-135 degrees week 26 / >135 degrees week 52 | 33 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 45-89 degrees week 26 / >135 degrees week 52 | 6 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 45-89 degrees week 26 / 45-89 degrees week 52 | 17 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | <45 degrees week 26 / 45-89 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | >135 degrees week 26 / <45 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 90-135 degrees week 26 / <45 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 45-89 degrees week 26 / <45 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | <45 degrees week 26 / <45 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | <45 degrees week 26 / >135 degrees week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | >135 degrees week 26 / 90-135 degrees week 52 | 42 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 90-135 degrees week 26/ 90-135 degrees week 52 | 171 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 45-89 degrees week 26/ 90-135 degrees week 52 | 15 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | <45 degrees week 26/ 90-135 degrees week 52 | 2 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | >135 degrees week 26 / 45-89 degrees week 52 | 1 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52 | 90-135 degrees week 26 / 45-89 degrees week 52 | 12 participants |
Primary
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Local warmth of the target knee was recorded as Yes (warmth present) or No (knee was not warmer than expected).
Time frame: weeks 26 and 52
Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52 | Yes week 26 / yes week 52 | 2 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52 | No week 26 / yes week 52 | 11 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52 | Yes week 26 / no week 52 | 11 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52 | No week 26 / no week 52 | 353 participants |
Primary
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Redness of the knee was subjectively rated as Yes (knee was red) and No (knee was not red).
Time frame: weeks 26 and 52
Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52 | Yes week 26 / no week 52 | 4 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52 | No week 26 / no week 52 | 373 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52 | Yes week 26 / yes week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52 | No week 26 / yes week 52 | 0 participants |
Primary
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Number of participants in various categories of target knee joint examination findings from baseline (week 26 pre-injection) to week 52. Tenderness of the knee was subjectively rated by participants as none, mild, moderate or severe.
Time frame: weeks 26 and 52
Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | None week 26 / none week 52 | 129 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Moderate week 26 / moderate week 52 | 9 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Severe week 26 / moderate week 52 | 1 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | None week 26 / severe week 52 | 1 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Mild week 26 / none week 52 | 44 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Moderate week 26 / none week 52 | 5 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Severe week 26 / none week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | None week 26 / mild week 52 | 61 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Mild week 26 / mild week 52 | 75 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Moderate week 26 / mild week 52 | 17 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Severe week 26 / mild week 52 | 0 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | None week 26 / moderate week 52 | 18 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Mild week 26 / moderate week 52 | 15 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Mild week 26 / severe week 52 | 1 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Moderate week 26 / severe week 52 | 1 participants |
| EUFLEXXA™ Double-blind | Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52 | Severe week 26 / severe week 52 | 0 participants |
Secondary
Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52.
The change in the number of tablets of study-specific acetaminophen taken per week as a rescue medication from knee pain.
Time frame: Extension baseline (week 26 pre-dose), week 52
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52. | 9.5 tablets per week | Standard Deviation 11.9 |
Secondary
Change From Baseline in Patient Global Assessment of Knee Pain at Week 26
Participant assessment of knee pain evaluated on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain; a score of 100 millimeters means extreme pain.
Time frame: Weeks 0 and 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Change From Baseline in Patient Global Assessment of Knee Pain at Week 26 | -22.0 units on a scale | Standard Deviation 30.38 |
| Placebo Double-blind | Change From Baseline in Patient Global Assessment of Knee Pain at Week 26 | -17.8 units on a scale | Standard Deviation 28.82 |
Secondary
Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26.
The change in the number of tablets of 500 milligram acetaminophen used in a week as rescue medication is compared at weeks 0 and weeks 26.
Time frame: Weeks 0 and 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26. | 12.7 tablets per week | Standard Deviation 14.56 |
| Placebo Double-blind | Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26. | 12.9 tablets per week | Standard Deviation 15.23 |
Secondary
Mean Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Extension Study
The mean difference in participant pain as measured by participants during a walk of 50 feet in length between the baseline (week 26 pre-dose) and week 52 scores. Scores are measured on a visual analog scale of 100 millimeters, with a score of 0 millimeters meaning there was no pain observed; a score of 100 millimeters meaning extreme pain was observed.
Time frame: Extension baseline (week 26), week 52
Population: Intent to treat population. No imputation for missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Mean Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Extension Study | -7.8 units on a scale | Standard Deviation 23.59 |
Secondary
Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26
The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' bodily pain scores. The questionnaire is completed by participants.
Time frame: weeks 0 and 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26 | 3.85 units on a scale | Standard Deviation 9.93 |
| Placebo Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26 | 2.94 units on a scale | Standard Deviation 9.56 |
Secondary
Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26
The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' general health scores. The questionnaire is completed by participants.
Time frame: weeks 0 and 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26 | 1.38 units on a scale | Standard Deviation 6.22 |
| Placebo Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26 | 0.19 units on a scale | Standard Deviation 6.75 |
Secondary
Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26
The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. The questionnaire is completed by participants. This table summarizes the change from baseline in participants' physical health.
Time frame: Weeks 0, 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26 | 4.55 units on a scale | Standard Deviation 8.5 |
| Placebo Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26 | 2.71 units on a scale | Standard Deviation 8.58 |
Secondary
Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26
The SF-36 questionnaire yields a score for each domain of health. All domains are scored on a scale from 0 (negative health) to 100 (positive health), with 100 representing the best possible health state. This table summarizes the change from baseline in participants' physical function. The questionnaire is completed by participants.
Time frame: Weeks 0, 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26 | 4.77 units on a scale | Standard Deviation 9.65 |
| Placebo Double-blind | Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26 | 3.18 units on a scale | Standard Deviation 9.05 |
Secondary
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12
Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter.
Time frame: Week 12
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12 | Yes | 173 participants |
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12 | No | 90 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12 | Yes | 167 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12 | No | 107 participants |
p-value: 0.202Chi-squared
Secondary
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26
Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter.
Time frame: Week 26
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26 | No | 85 participants |
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26 | Yes | 169 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26 | Yes | 155 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26 | No | 109 participants |
p-value: 0.047Chi-squared
Secondary
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52
Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer:YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter.
Time frame: Week 52 (Extension Study)
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52 | Yes | 144 participants |
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52 | No | 230 participants |
Secondary
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12
Responders are identified based on a calculation of three scales: WOMAC (A) pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter.
Time frame: Week 12
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12 | Yes | 153 participants |
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12 | No | 109 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12 | Yes | 155 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12 | No | 118 participants |
p-value: 0.618Chi-squared
Secondary
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26
Responders are identified based on a calculation of three scales: WOMAC (A) pain, function and global assessment scales. Each of the individual scales was completed by the participant. A participant was a responder (answer: YES) if there was high improvement in pain or function (\>=50 percent and absolute change of \>=20 millimeters), or improvement in at least two of three categories: Pain and/or Function and/or Patient Global Assessment scales of \>=20 percent and absolute change \>=10 millimeter.
Time frame: week 26
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26 | Yes | 155 participants |
| EUFLEXXA™ Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26 | No | 98 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26 | Yes | 137 participants |
| Placebo Double-blind | Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26 | No | 127 participants |
p-value: 0.028Chi-squared
Secondary
Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test
Yes represents the number of participants whose pain during a walk of 50 feet in length was improved at week 26 over baseline by at least 20 millimeters. Pain was evaluated on a 100 millimeter visual analog scale by participants. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed.
Time frame: Weeks 0 and 26
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test | Yes | 145 participants |
| EUFLEXXA™ Double-blind | Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test | No | 106 participants |
| Placebo Double-blind | Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test | Yes | 120 participants |
| Placebo Double-blind | Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test | No | 139 participants |
p-value: 0.006Chi-squared
Secondary
Observed Pain Scores on the 50-foot Walk Test During the Extension Study
Participant pain during a walk of 50 feet in length was evaluated by participants on a 100 millimeter visual analog scale. A score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed.
Time frame: Baseline (week 26), week 52
Population: Intent to treat population. No imputation for missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EUFLEXXA™ Double-blind | Observed Pain Scores on the 50-foot Walk Test During the Extension Study | Extension baseline (week 26) (n=418) | 33.1 units on a scale | Standard Deviation 27.26 |
| EUFLEXXA™ Double-blind | Observed Pain Scores on the 50-foot Walk Test During the Extension Study | Week 52 (n=372) | 24.7 units on a scale | Standard Deviation 24.88 |
Secondary
Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study for a Subpopulation of Participants With More Severe Knee Pain
Percent difference in participant pain during a walk of 50 feet in length between the mean screening (week -1) and baseline(week 0) scores, and week 26 scores. Scores are recorded by participants and measured on a visual analog scale of 100 millimeters, with 0 millimeters meaning there was no pain observed; 100 millimeters meaning extreme pain was observed.
Time frame: weeks -1, 0, and 26
Population: Intent to treat population. A subpopulation of patients with more severe knee pain, as measured by having a greater than or equal to 41 millimeter screening score on the 50-foot walk test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study for a Subpopulation of Participants With More Severe Knee Pain | -50.5 percentage change from baseline score | Standard Deviation 42.26 |
| Placebo Double-blind | Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study for a Subpopulation of Participants With More Severe Knee Pain | -36.8 percentage change from baseline score | Standard Deviation 53.71 |
p-value: 0.001ANCOVA
Secondary
Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
The percent difference in participant pain recorded by the participant during a walk of 50 feet in length between the screening (week -1) and week 26 scores. Scores are measured on a visual analog scale of 100 millimeters; a score of 0 millimeters means there was no pain observed; a score of 100 millimeters means extreme pain was observed.
Time frame: weeks -1 and 26
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EUFLEXXA™ Double-blind | Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | -29.3 percent change from screening value | Standard Deviation 277.14 |
| Placebo Double-blind | Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study | -38.4 percent change from screening value | Standard Deviation 55.25 |
p-value: 0.008ANCOVA