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

NCT00379236 | Completed Results

• 1 other identifier: 2005-01D
• Study Type: interventional
• Target: 588
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (6)

• 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.

  Weeks 0, 26

• 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.

  Weeks 0 and 26

• 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.

  weeks 26 and 52

• 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.

  weeks 26 and 52

• 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).

  weeks 26 and 52

• 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).

  weeks 26 and 52

Secondary Outcomes (17)

• Percent Change From Screening in Observed Pain Scores on 50-foot Walk Test During the Double-blind Study

  weeks -1 and 26

• 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

• Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 12

  Week 12

• Number of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the 50-Foot Walk Test at Week 26

  Week 26

• 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

Study Arms (3)

EUFLEXXA™ Double-blind

EXPERIMENTAL

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.

Device: EUFLEXXA™

Placebo Double-blind

PLACEBO COMPARATOR

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.

Device: placebo

EUFLEXXA™ Open Label

EXPERIMENTAL

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.

Device: EUFLEXXA™

Interventions

EUFLEXXA™ 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.

EUFLEXXA™ Double-blind; EUFLEXXA™ Open Label

placebo 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.

Placebo Double-blind

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic OA of target knee confirmed by ACR Criteria
• 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
• 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
• 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.
• Ability to perform procedures required of the pain index evaluations (unassisted walking 50 feet on a flat surface and going up and down stairs).
• Willingness and ability to complete efficacy and safety questionnaires and ability to read and understand study instructions
• Signed study-specific Subject Informed Consent Form

You may not qualify if:

• Any major injury (including sports injuries) to the target knee within the 12 months prior to the Screening Visit
• 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
• Prior articular procedures, such as transplants or ligament reconstruction to the target knee
• Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis
• Gout or calcium pyrophosphate (pseudogout) diseases that have flared within the previous 6 months prior to the Screening Visit
• X-ray findings of acute fractures, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee
• Osteonecrosis of either knee
• Fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication
• Significant anterior knee pain due to diagnosed isolated patella-femoral syndrome or chondromalacia in the target knee
• Significant target knee joint infection or skin disorder/infection within the previous 6 months prior to study enrollment
• Symptomatic OA of the hips, spine, or ankle, if it would interfere with the evaluation of the target knee
• Known hypersensitivity to acetaminophen, EUFLEXXA™, or Phosphate buffered saline solution
• 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
• Recurrent medical history of severe allergic or immune-mediated reactions or other immune disorders
• Vascular insufficiency of lower limbs or peripheral neuropathy severe enough to interfere with the study evaluation

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (1)

Investigational site

Los Angeles, California, 90025-1670, United States

Location

Related Publications (1)

• 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.

  PMID: 21820521 RESULT

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Results Point of Contact

• Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2006
• First Posted: September 21, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: May 1, 2008
• Last Updated: December 28, 2011
• Results First Posted: December 10, 2009

Record last verified: 2011-12

Locations

US (1)