Investigation of 1.2% Sodium Hyaluronate for Treatment of Painful Chronic Osteoarthritis of the Knee

Osteoarthritis of the Knee Clinical Trial

Official title:

A 26 Week, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Single Intra-Articular Injection 1.2% Sodium Hyaluronate for Treatment of Painful Osteoarthritis of the Knee, With Optional 26-Week Open-Label Safety Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00988091
• Other study ID #: 2009-03
• Status: Completed
• Phase: Phase 3
• First received: September 29, 2009
• Last updated: June 13, 2012
• Start date: September 2009
• Est. completion date: April 2011

Study information

• Verified date: June 2012
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Subjects with chronic osteoarthritis of the knee will be assigned to receive an injection of either 1.2% sodium hyaluronate or buffered saline to evaluate its effectiveness and safety for 26 weeks. After 26 weeks, subjects can elect to receive a second injection of 1.2% sodium hyaluronate and be followed for another 26 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 596
• Est. completion date: April 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Chronic osteoarthritis (OA) of target knee confirmed by American College of Rheumatology (ACR) Criteria.

• Pain due to OA in target knee present for at least 6 months.

• During Screening and Baseline visits, subjects will require a visual analog scale (VAS) score (100 mm) of = 41 mm and = 90 mm, recorded immediately following a 50-foot walk, AND at Baseline, cannot have decreased >10mm (improvement) from Screening.

• A bilateral standing anteroposterior (AP) X-ray confirming OA of the target knee.

• Ability and willingness to use only acetaminophen as the analgesic (rescue) study medication

• 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 Subject Informed Consent Form

Exclusion Criteria:

• Any major injury (including sports injuries) to the target knee within the prior 12 months.

• Any surgery to the target knee, hip and contralateral hip within the prior 12 months.

• Major and minor articular procedures

• Inflammatory arthropathies such as rheumatoid arthritis, lupus arthropathy, or psoriatic arthritis.

• Gout or calcium pyrophosphate (pseudogout) diseases of the target knee that have flared within the previous 6 months.

• 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, sodium hyaluronate, 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.

• Current treatment or treatment within the previous 2 years prior to Screening for any malignancy unless specific written permission is provided by the Sponsor (excluding basal cell or squamous cell carcinoma of the skin).

• Chronic liver disease and active liver disease based on liver profile of aspartate aminotransferase (AST), alanine transaminase (ALT), and conjugated bilirubin >2 times the upper limit of normal.

• Renal insufficiency based on serum creatinine >2.0 mg/dL.

• Any clinically significant laboratory value based on clinical history that the Investigator feels may affect the study evaluation.

• 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.

• Current alcoholism, and/or any known current addiction to pain medications.

• Any clinically significant finding that would place the patient at health risk, impact the study, or affect the completion of the study.

• Any psychiatric illness that would prevent comprehension of the details and nature of the study.

• Participation in any experimental device study within 6 months prior to the Screening, or an experimental drug study within 1 month prior to the Screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis of the Knee
• Osteoarthritis, Knee

Intervention

Device:
• 1.2% Sodium Hyaluronate
IA-BioHA is supplied in a disposable 7 ml nominal volume glass syringe containing 60 mg/5 ml of 1.2% sodium hyaluronate. Participants are given a single injection in the target knee on Day 1 of the double-blind period and optionally on the first day of the open-label period (approximately week 27).
• Buffered Saline
IA-SA is supplied in a disposable 7 ml nominal volume glass syringe containing 5 ml of phosphate buffered saline. Participants are given a single injection in the target knee on Day 1 of the double-blind period.

Locations

Country	Name	City	State
United States	International Physicians Research	Aventura	Florida
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Southbay Pharma Research	Buena Park	California
United States	Providence Clinical Research	Burbank	California
United States	Colorado Arthritis Center, PC	Englewood	Colorado
United States	Investigational Site	Ft. Lauderdale	Florida
United States	Texas Orthopedic Specialists, PA	Grapevine	Texas
United States	Apex Clinical Trials, LLC	Homewood	Alabama
United States	St. Joseph's Mercy Clinic	Hot Springs	Arkansas
United States	Memorial Bone & Joint Research Foundation	Houston	Texas
United States	Holston Medical Group	Kingsport	Tennessee
United States	Triwest Research Associates	La Mesa	California
United States	Sunrise Medical Research	Lauderdale Lakes	Florida
United States	Tri-County Orthopaedic Center	Leesburg	Florida
United States	Rx Medical Research of Arkansas, Inc	Little Rock	Arkansas
United States	UCLA-Division of Rheumatology	Los Angeles	California
United States	Georgia Institute for Clinical Research	Marietta	Georgia
United States	Pinnacle Orthopaedics and Sports Medicine	Marietta	Georgia
United States	McKenzie Medical Center	McKenzie	Tennessee
United States	Palmetto Medical Research	Mt. Pleasant	South Carolina
United States	Research Department, Bone & Joint Hospital at St. Anthony	Oklahoma City	Oklahoma
United States	New Jersey Physicians, LLC	Passaic	New Jersey
United States	Black Hills Orthopedic & Spine Center	Rapid City	South Dakota
United States	Discovery Clinical Trials (DCT) - Stone Oak, LLC	San Antonio	Texas
United States	Investigational Site	Santa Barbara	California
United States	Lee Research Institute	Shawnee	Kansas
United States	Palmetto Clinical Trial Services, LLC	Simpsonville	South Carolina
United States	New England Research Associates, LLC	Trumball	Connecticut
United States	Tucson Orthopaedic Institute	Tucson	Arizona
United States	Omega Medical Research	Warwick	Rhode Island
United States	Clinical Research Center LLC	Wellington	Florida
United States	Front Range Clinical Research	Wheatridge	Colorado
United States	Professional Research Network of Kansas	Wichita	Kansas
United States	National Pain Research Institute, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Visual Analogue Score (VAS) Pain Score of the 50-foot Walk Test at Week 26	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 recorded 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. Change from baseline is calculated: week 26 VAS Pain Score - Baseline VAS Pain Score.	Day 0 (baseline) through Week 26	No
Secondary	Change From Baseline in Western Ontario McMaster University Osteoarthritis Index (WOMAC) Disability Scores at Week 26	Adjusted mean of all WOMAC pain, stiffness and physical function subscores on Visual Analog Scale (VAS) of 100 mm; 0 mm = no pain, stiffness and difficulty; 100 mm = extreme pain, stiffness and difficulty. Change from baseline calculated as: Week 26 minus baseline.	Day 0 (baseline), week 26	No
Secondary	Percentage of Participants With a >=20mm Improvement Between Baseline and Week 26 on the 50 Foot Walk Visual Analogue Scale (VAS) Pain Score.	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 recorded 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. Change from baseline is calculated: week 26 VAS Pain Score - Baseline VAS Pain Score. The percent of participants who showed a 20mm or greater improvement in the pain scores at week 26 compared to baseline are reported.	Day 0 (baseline), Week 26	No
Secondary	Subjective Patient Assessment of Treatment at Week 26	At the end of the double-blind period (week 26), participants were asked: "Are you satisfied with the results of the injection?" Answers could be: 1=dissatisfied; 2=slightly satisfied; 3=satisfied; or 4=very satisfied.	Week 26	No
Secondary	Number of Tablets of Rescue Medication Used Between Visits	Acetaminophen (500-mg tablets) was provided to study participants as a rescue medication in case they needed a pain medication during the study. The mean number of tablets of rescue medication should have been summarized, however the data was not captured in a reliable way and is therefore not reported.	Day 1 to week 26	No
Secondary	Change From Baseline in Patient Global Assessment at Week 26	Participants were asked to mark along a 100mm visual analog scale (VAS) indicating the point best representing the severity of the knee pain that day. The left side of the VAS was 0=no pain and the right side was 100 = extreme pain. Change from baseline was calculated as Week 26 - Baseline.	Day 0 (baseline), Week 26	No
Secondary	Percentage of Observed Osteoarthritis Research Society International (OARSI30) Responders Using the Visual Analogue Scale (VAS) to Assess Pain Following a 50-foot Walk at Week 26	Responders are identified based on a calculation of three scales: 50-foot walk test for pain, function (WOMAC Disability score) and global assessment (Patient Global Assessment Score) scales. Each of the individual scales was completed by the participant. A responder showed considerable 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. Response at Week 26 is compared to baseline.	Day 0 (baseline), week 26	No