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

NCT ID: NCT00379236

Last Updated: 2011-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 588 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2008-05-31

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.

Conditions

Osteoarthritis, Knee

Keywords

osteoarthritis; knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

EUFLEXXA™ Double-blind

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.

Group Type: EXPERIMENTAL

EUFLEXXA™

Intervention Type: DEVICE

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.

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DEVICE

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.

EUFLEXXA™ Open Label

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.

Group Type: EXPERIMENTAL

EUFLEXXA™

Intervention Type: DEVICE

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.

Interventions

EUFLEXXA™

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.

Intervention Type: DEVICE

placebo

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.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ferring Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Development Support

Role: STUDY_DIRECTOR

Ferring Pharmaceuticals

Locations

Investigational site

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21820521 (View on PubMed)

Other Identifiers

2005-01D

Identifier Type: -

Identifier Source: org_study_id