Clinical trial NCT00379236: A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee
Official title: A Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee, With an Open-Label Safety Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: osteoarthritis
knee
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2006-09-21
Enrollment: 588
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
timeFrame: Weeks 0, 26
measure: Percent Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
timeFrame: Weeks 0 and 26
measure: Shifts From Extension Study Baseline (Week 26) in Range of Motion Findings at Week 52
timeFrame: weeks 26 and 52
measure: Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Tenderness at Week 52
timeFrame: weeks 26 and 52
measure: Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Local Warmth at Week 52
timeFrame: weeks 26 and 52
measure: Shifts From Extension Study Baseline (Week 26) in Ratings of Knee Redness at Week 52
timeFrame: weeks 26 and 52
Secondary outcomes:
measure: Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study
timeFrame: weeks -1 and 26
measure: 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
timeFrame: weeks -1, 0, and 26
measure: Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12
timeFrame: Week 12
measure: Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26
timeFrame: Week 26
measure: Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 12
timeFrame: Week 12
measure: Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Western Ontario McMaster University Osteoarthritis Index (WOMAC A) Pain Scale at Week 26
timeFrame: week 26
measure: Change From Baseline in Patient Global Assessment of Knee Pain at Week 26
timeFrame: Weeks 0 and 26
measure: Change From Baseline in the Number of Tablets of Rescue Medication Used at Week 26.
timeFrame: Weeks 0 and 26
measure: Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Function (PF) Score at Week 26
timeFrame: Weeks 0, 26
measure: Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Bodily Pain(BP) Score at Week 26
timeFrame: weeks 0 and 26
measure: Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) General Health(GH) Score at Week 26
timeFrame: weeks 0 and 26
measure: Mean Change From Baseline in Short Form 36 Questionnaire (SF-36) Physical Component Summary (PCS) Score at Week 26
timeFrame: Weeks 0, 26
measure: Number of Participants With 20 Millimeter or Greater Improvement in Pain Scores on the 50-foot Walk Test
timeFrame: Weeks 0 and 26
measure: Observed Pain Scores on the 50-foot Walk Test During the Extension Study
timeFrame: Baseline (week 26), week 52
measure: Mean Change From Baseline in Observed Pain Scores on 50-foot Walk Test During the Extension Study
timeFrame: Extension baseline (week 26), week 52
measure: Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 52
timeFrame: Week 52 (Extension Study)
measure: Change From Baseline (Extension Study Week 26) in Use of Rescue Medication at Week 52.
timeFrame: Extension baseline (week 26 pre-dose), week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Investigational site
state: California
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References:
citation: Altman RD, Rosen JE, Bloch DA, Hatoum HT. Safety and efficacy of retreatment with a bioengineered hyaluronate for painful osteoarthritis of the knee: results of the open-label Extension Study of the FLEXX Trial. Osteoarthritis Cartilage. 2011 Oct;19(10):1169-75. doi: 10.1016/j.joca.2011.07.001. Epub 2011 Jul 23.