Trial Outcomes & Findings for A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee (NCT NCT00379236)
NCT ID: NCT00379236
Last Updated: 2011-12-28
Results Overview
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.
COMPLETED
NA
588 participants
Weeks 0, 26
2011-12-28
Participant Flow
A total of 821 patients were screened.
Participant milestones
| Measure |
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.
|
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.
|
EUFLEXXA™ Extension Study
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 26, 27 and 28. Patients were followed for 26 additional weeks (to week 52) following the first injection.
|
|---|---|---|---|
|
Double-blind
STARTED
|
293
|
295
|
0
|
|
Double-blind
COMPLETED
|
257
|
259
|
0
|
|
Double-blind
NOT COMPLETED
|
36
|
36
|
0
|
|
Open-label Extension
STARTED
|
0
|
0
|
433
|
|
Open-label Extension
COMPLETED
|
0
|
0
|
378
|
|
Open-label Extension
NOT COMPLETED
|
0
|
0
|
55
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
EUFLEXXA™ Extension Study
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 26, 27 and 28. Patients were followed for 26 additional weeks (to week 52) following the first injection.
|
|---|---|---|---|
|
Double-blind
Adverse Event
|
11
|
6
|
0
|
|
Double-blind
Protocol Violation
|
3
|
3
|
0
|
|
Double-blind
Withdrawal by Subject
|
12
|
13
|
0
|
|
Double-blind
Lost to Follow-up
|
4
|
3
|
0
|
|
Double-blind
Use of exclusionary medication
|
1
|
2
|
0
|
|
Double-blind
Other
|
3
|
7
|
0
|
|
Double-blind
Data could not be retrieved
|
2
|
2
|
0
|
|
Open-label Extension
Adverse Event
|
0
|
0
|
13
|
|
Open-label Extension
Protocol Violation
|
0
|
0
|
7
|
|
Open-label Extension
Withdrawal by Subject
|
0
|
0
|
13
|
|
Open-label Extension
Lost to Follow-up
|
0
|
0
|
12
|
|
Open-label Extension
Use of exclusionary medication
|
0
|
0
|
3
|
|
Open-label Extension
Other
|
0
|
0
|
7
|
Baseline Characteristics
A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee
Baseline characteristics by cohort
| Measure |
EUFLEXXA™ Double-blind
n=293 Participants
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.
|
Placebo Double-blind
n=295 Participants
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.
|
Total
n=588 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
62.5 years
STANDARD_DEVIATION 10.62 • n=5 Participants
|
60.8 years
STANDARD_DEVIATION 10.31 • n=7 Participants
|
61.6 years
STANDARD_DEVIATION 10.50 • n=5 Participants
|
|
Sex: Female, Male
Female
|
185 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
371 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
108 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
217 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
231 participants
n=5 Participants
|
228 participants
n=7 Participants
|
459 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
26 participants
n=5 Participants
|
33 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
29 participants
n=5 Participants
|
25 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
293 participants
n=5 Participants
|
295 participants
n=7 Participants
|
588 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
32.36 kilograms/meters square
STANDARD_DEVIATION 7.446 • n=5 Participants
|
33.03 kilograms/meters square
STANDARD_DEVIATION 7.444 • n=7 Participants
|
32.70 kilograms/meters square
STANDARD_DEVIATION 7.446 • n=5 Participants
|
|
Weight
|
91.0 kilograms
STANDARD_DEVIATION 21.95 • n=5 Participants
|
92.8 kilograms
STANDARD_DEVIATION 21.68 • n=7 Participants
|
91.9 kilograms
STANDARD_DEVIATION 21.81 • n=5 Participants
|
PRIMARY outcome
Timeframe: Weeks 0, 26Population: Intent to treat (ITT) population.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=291 Participants
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.
|
Placebo Double-blind
n=295 Participants
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.
|
|---|---|---|
|
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
|
54.7 units on a scale
Standard Deviation 21.81
|
|
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
|
36.1 units on a scale
Standard Deviation 28.55
|
PRIMARY outcome
Timeframe: Weeks 0 and 26Population: Intent to treat population.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=251 Participants
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.
|
Placebo Double-blind
n=259 Participants
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.
|
|---|---|---|
|
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 117.20
|
-14.9 percent change from baseline value
Standard Deviation 114.87
|
PRIMARY outcome
Timeframe: weeks 26 and 52Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=375 Participants
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.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
PRIMARY outcome
Timeframe: weeks 26 and 52Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=377 Participants
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.
|
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.
|
|---|---|---|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
None week 26 / none week 52
|
129 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Mild week 26 / none week 52
|
44 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Moderate week 26 / none week 52
|
5 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Severe week 26 / none week 52
|
0 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
None week 26 / mild week 52
|
61 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Mild week 26 / mild week 52
|
75 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Moderate week 26 / mild week 52
|
17 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Severe week 26 / mild week 52
|
0 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
None week 26 / moderate week 52
|
18 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Mild week 26 / moderate week 52
|
15 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Moderate week 26 / moderate week 52
|
9 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Severe week 26 / moderate week 52
|
1 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
None week 26 / severe week 52
|
1 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Mild week 26 / severe week 52
|
1 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Moderate week 26 / severe week 52
|
1 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
Severe week 26 / severe week 52
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: weeks 26 and 52Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
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).
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=377 Participants
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.
|
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.
|
|---|---|---|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
Yes week 26 / yes week 52
|
2 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
No week 26 / yes week 52
|
11 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
Yes week 26 / no week 52
|
11 participants
|
—
|
|
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 outcome
Timeframe: weeks 26 and 52Population: Safety population which includes all participants who received at least one injection during the extension phase of the study.
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).
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=377 Participants
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.
|
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.
|
|---|---|---|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
Yes week 26 / yes week 52
|
0 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
No week 26 / yes week 52
|
0 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
Yes week 26 / no week 52
|
4 participants
|
—
|
|
Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
No week 26 / no week 52
|
373 participants
|
—
|
SECONDARY outcome
Timeframe: weeks -1 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=249 Participants
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.
|
Placebo Double-blind
n=259 Participants
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.
|
|---|---|---|
|
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
|
-38.4 percent change from screening value
Standard Deviation 55.25
|
SECONDARY outcome
Timeframe: weeks -1, 0, and 26Population: 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.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=239 Participants
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.
|
Placebo Double-blind
n=254 Participants
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.
|
|---|---|---|
|
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
|
-36.8 percentage change from baseline score
Standard Deviation 53.71
|
SECONDARY outcome
Timeframe: Week 12Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=263 Participants
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.
|
Placebo Double-blind
n=274 Participants
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.
|
|---|---|---|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12
Yes
|
173 participants
|
167 participants
|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12
No
|
90 participants
|
107 participants
|
SECONDARY outcome
Timeframe: Week 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=254 Participants
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.
|
Placebo Double-blind
n=264 Participants
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.
|
|---|---|---|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26
Yes
|
169 participants
|
155 participants
|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26
No
|
85 participants
|
109 participants
|
SECONDARY outcome
Timeframe: Week 12Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=262 Participants
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.
|
Placebo Double-blind
n=273 Participants
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.
|
|---|---|---|
|
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
|
155 participants
|
|
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
|
118 participants
|
SECONDARY outcome
Timeframe: week 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=253 Participants
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.
|
Placebo Double-blind
n=264 Participants
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.
|
|---|---|---|
|
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
|
137 participants
|
|
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
|
127 participants
|
SECONDARY outcome
Timeframe: Weeks 0 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=253 Participants
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.
|
Placebo Double-blind
n=263 Participants
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.
|
|---|---|---|
|
Change From Baseline in Patient Global Assessment of Knee Pain at Week 26
|
-22.0 units on a scale
Standard Deviation 30.38
|
-17.8 units on a scale
Standard Deviation 28.82
|
SECONDARY outcome
Timeframe: Weeks 0 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=232 Participants
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.
|
Placebo Double-blind
n=240 Participants
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.
|
|---|---|---|
|
Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26.
|
12.7 tablets per week
Standard Deviation 14.56
|
12.9 tablets per week
Standard Deviation 15.23
|
SECONDARY outcome
Timeframe: Weeks 0, 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=253 Participants
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.
|
Placebo Double-blind
n=264 Participants
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.
|
|---|---|---|
|
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
|
3.18 units on a scale
Standard Deviation 9.05
|
SECONDARY outcome
Timeframe: weeks 0 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=254 Participants
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.
|
Placebo Double-blind
n=265 Participants
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.
|
|---|---|---|
|
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
|
2.94 units on a scale
Standard Deviation 9.56
|
SECONDARY outcome
Timeframe: weeks 0 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=253 Participants
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.
|
Placebo Double-blind
n=265 Participants
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.
|
|---|---|---|
|
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
|
0.19 units on a scale
Standard Deviation 6.75
|
SECONDARY outcome
Timeframe: Weeks 0, 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=251 Participants
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.
|
Placebo Double-blind
n=263 Participants
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.
|
|---|---|---|
|
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 8.50
|
2.71 units on a scale
Standard Deviation 8.58
|
SECONDARY outcome
Timeframe: Weeks 0 and 26Population: Intent to treat population
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=251 Participants
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.
|
Placebo Double-blind
n=259 Participants
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.
|
|---|---|---|
|
Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test
Yes
|
145 participants
|
120 participants
|
|
Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test
No
|
106 participants
|
139 participants
|
SECONDARY outcome
Timeframe: Baseline (week 26), week 52Population: Intent to treat population. No imputation for missing values.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=425 Participants
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.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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 outcome
Timeframe: Extension baseline (week 26), week 52Population: Intent to treat population. No imputation for missing values.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=367 Participants
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.
|
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.
|
|---|---|---|
|
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 outcome
Timeframe: Week 52 (Extension Study)Population: Intent to treat population.
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.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=374 Participants
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.
|
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.
|
|---|---|---|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52
Yes
|
144 participants
|
—
|
|
Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52
No
|
230 participants
|
—
|
SECONDARY outcome
Timeframe: Extension baseline (week 26 pre-dose), week 52Population: Intent to treat population
The change in the number of tablets of study-specific acetaminophen taken per week as a rescue medication from knee pain.
Outcome measures
| Measure |
EUFLEXXA™ Double-blind
n=311 Participants
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.
|
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.
|
|---|---|---|
|
Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52.
|
9.5 tablets per week
Standard Deviation 11.90
|
—
|
Adverse Events
EUFLEXXA™ Double-blind
Placebo Double-blind
EUFLEXXA™ Extension Study
Serious adverse events
| Measure |
EUFLEXXA™ Double-blind
n=293 participants at risk
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.
|
Placebo Double-blind
n=295 participants at risk
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.
|
EUFLEXXA™ Extension Study
n=433 participants at risk
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 26, 27 and 28. Patients were followed for 26 additional weeks (to week 52) following the first injection.
|
|---|---|---|---|
|
Cardiac disorders
acute myocardial infarction
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Cardiac disorders
angina unstable
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Cardiac disorders
arrhythmia
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Gastrointestinal disorders
abdominal pain
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Gastrointestinal disorders
salivary gland mass
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Gastrointestinal disorders
umbilical hernia
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Infections and infestations
pneumonia
|
0.68%
2/293 • Number of events 2
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Infections and infestations
appendicitis
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Infections and infestations
gastroenteritis salmonella
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Injury, poisoning and procedural complications
ankle fracture
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Injury, poisoning and procedural complications
injury
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.23%
1/433 • Number of events 1
|
|
Injury, poisoning and procedural complications
lower limb fracture
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Injury, poisoning and procedural complications
spinal compression fracture
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Metabolism and nutrition disorders
hyponatraemia
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.23%
1/433 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
pancreatic carcinoma
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Nervous system disorders
transient ischaemic attack
|
0.34%
1/293 • Number of events 1
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Skin and subcutaneous tissue disorders
erythema
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Surgical and medical procedures
hysterectomy
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Surgical and medical procedures
oophorectomy bilateral
|
0.34%
1/293 • Number of events 1
|
0.00%
0/295
|
0.00%
0/433
|
|
Vascular disorders
deep vein thrombosis
|
0.00%
0/293
|
0.34%
1/295 • Number of events 1
|
0.00%
0/433
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Cardiac disorders
atrial fibrillation
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Cardiac disorders
mitral valve incompetence
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Cardiac disorders
myocardial infarction
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Ear and labyrinth disorders
vertigo
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Hepatobiliary disorders
cholelithiasis
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Infections and infestations
bacterial bronchitis
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Nervous system disorders
cerebrovascular accident
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Psychiatric disorders
depression
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
asthma
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pneumothorax
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Surgical and medical procedures
cholecystectomy
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Surgical and medical procedures
intervertebral disc operation
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Surgical and medical procedures
spinal fusion surgery
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
|
Vascular disorders
hypertension
|
0.00%
0/293
|
0.00%
0/295
|
0.23%
1/433 • Number of events 1
|
Other adverse events
| Measure |
EUFLEXXA™ Double-blind
n=293 participants at risk
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.
|
Placebo Double-blind
n=295 participants at risk
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.
|
EUFLEXXA™ Extension Study
n=433 participants at risk
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 26, 27 and 28. Patients were followed for 26 additional weeks (to week 52) following the first injection.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.2%
27/293 • Number of events 27
|
11.9%
35/295 • Number of events 35
|
9.9%
43/433 • Number of events 43
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript.
- Publication restrictions are in place
Restriction type: OTHER