A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee

Ferring

Status: Completed

Conditions: Osteoarthritis, Knee

Treatments: Device: placebo; Device: EUFLEXXA™

Study type: Interventional

Funder types: Industry

Identifiers

NCT00379236

2005-01D

Details and patient eligibility

About

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.

Enrollment: 588 patients

Sex: All

Ages: 40+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

588 participants in 3 patient groups, including a placebo group

EUFLEXXA™ Double-blind

Experimental group

Description:

Each subject received 3 single-dose injections of EUFLEXXA™ into the target knee; one injection per week at weeks 0, 1 and 2. Patients were followed for 26 weeks following the first injection.

Treatment:

Device: EUFLEXXA™

Placebo Double-blind

Placebo Comparator group

Description:

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.

Treatment:

Device: placebo

EUFLEXXA™ Open Label

Experimental group

Description:

All patients who participated in the 26 week double-blind study (including participants randomized to the placebo treatment group) and elected to participate in the open label extension, received three injections of EUFLEXXA™ in the target knee. Injections were given once a week on weeks 26, 27 and 28.

Treatment:

Device: EUFLEXXA™