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CompletedNCT00988091Updated Jun 15, 2012Results posted

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

A Phase 3 interventional study of 1.2% Sodium Hyaluronate and Buffered Saline in Osteoarthritis of the Knee, sponsored by Ferring Pharmaceuticals. Completed at 34 sites in United States. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2012-06-15.

Sponsored by Ferring Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
596
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Osteoarthritis of the Knee
03

In context

Osteoarthritis

4,398 studies on the registry are indexed under Osteoarthritis; 582 are open to participants now.

This study's enrollment of 596 is above the median of 70 across 3,440 interventional studies indexed under Osteoarthritis.

Browse Osteoarthritis studies →

Lead sponsor

Ferring Pharmaceuticals is the lead sponsor of 244 studies on the registry; 4 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 13 (93%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
596 participants (actual)

Study arms

  • Placebo comparator
    IA-SA

    Each participant received a single intra-articular (IA) injection of buffered saline (SA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they could receive a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and be followed for an additional 26 weeks.

    Device: Buffered Saline

  • Experimental
    IA-BioHA

    Each participant received a single intra-articular (IA) injection of 1.2% sodium hyaluronate (BioHA) into the target knee, and was followed for a total of 26 weeks in the double-blind period. Participants had the option of continuing into the open-label period in which they received a single intra-articular injection of 1.2% sodium hyaluronate (IA-BioHA) into the target knee and were followed for an additional 26 weeks.

    Device: 1.2% Sodium Hyaluronate

Interventions

  • Device1.2% 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).

    Also known as: sodium hyaluronate

  • DeviceBuffered 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.

    Also known as: saline

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Day 0 (baseline) through Week 26

Secondary outcomes

  1. 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.

    Time frame: Day 0 (baseline), week 26

  2. 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.

    Time frame: Day 0 (baseline), Week 26

  3. 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.

    Time frame: Week 26

  4. 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.

    Time frame: Day 1 to week 26

  5. 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.

    Time frame: Day 0 (baseline), Week 26

  6. 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.

    Time frame: Day 0 (baseline), week 26

07

Results

Posted Jun 4, 2012

Participant flow

A total of 1007 subjects were screened for the double-blind period of the study, and 596 subjects were randomized and treated (safety population).

Double-blind Period
Participant flow — Double-blind Period
MilestoneIA-SAIA-BioHA
Started298298
Intent to treat population294295
Completed255251
Not completed4347
Withdrew: Withdrawal by subject1513
Withdrew: Lost to follow-up1214
Withdrew: Other88
Withdrew: Adverse event69
Withdrew: Use of exclusionary medication23
Open-label Period
Participant flow — Open-label Period
MilestoneIA-SAIA-BioHA
Started229225
Completed208192
Not completed2133
Withdrew: Adverse event47
Withdrew: Use of exclusionary medication11
Withdrew: Protocol violation11
Withdrew: Withdrawal by subject1016
Withdrew: Lost to follow-up35
Withdrew: Other23

Outcome measures

PrimaryChange 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.

Time frame:
Day 0 (baseline) through Week 26
Reported as:
Least squares mean · units on a scale
Change From Baseline in the Visual Analogue Score (VAS) Pain Score of the 50-foot Walk Test at Week 26
units on a scaleIA-SAIA-BioHA
Change From Baseline in the Visual Analogue Score (VAS) Pain Score of the 50-foot Walk Test at Week 26-33.48 ± 1.81-28.15 ± 1.82
Statistical analysis
  • IA-SA vs IA-BioHA · Mixed Models Repeated Measures ANCOVA · p = 0.034 (The p-value was not adjusted for multiple comparisons because there was a single treatment comparison for the primary endpoint. The a priori threshold for statistical significance was p \<0.05.) · Adjusted mean difference: 5.33 · 95% CI 0.41 to 10.24The analysis included baseline score as a covariate and study center as a stratification variable.
SecondaryChange 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.

Time frame:
Day 0 (baseline), week 26
Reported as:
Least squares mean · units on a scale
Change From Baseline in Western Ontario McMaster University Osteoarthritis Index (WOMAC) Disability Scores at Week 26
units on a scaleIA-SAIA-BioHA
Change From Baseline in Western Ontario McMaster University Osteoarthritis Index (WOMAC) Disability Scores at Week 26-21.72 ± 1.55-18.82 ± 1.57
Statistical analysis
  • IA-SA vs IA-BioHA · Mixed Models Repeated Measures ANCOVA · p = 0.175 (For secondary outcome measures, fixed-sequence testing was used in a sequentially rejective fashion. The a priori threshold for statistical significance was p \<0.05.) · Adjusted mean difference: 2.89 · 95% CI -1.29 to 7.08The analysis included baseline score as a covariate and study center as a stratification variable.
SecondaryPercentage 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.

Time frame:
Day 0 (baseline), Week 26
Reported as:
Number · percentage of participants
Percentage of Participants With a >=20mm Improvement Between Baseline and Week 26 on the 50 Foot Walk Visual Analogue Scale (VAS) Pain Score.
percentage of participantsIA-SAIA-BioHA
Percentage of Participants With a >=20mm Improvement Between Baseline and Week 26 on the 50 Foot Walk Visual Analogue Scale (VAS) Pain Score.66.860.9
Statistical analysis
  • IA-SA vs IA-BioHA · Regression, Logistic · p = 0.193 (For secondary outcome measures, fixed-sequence testing was used in a sequentially rejective fashion. The a priori threshold for statistical significance was p \<0.05.) · Odds ratio (or): 0.777 · 95% CI 0.532 to 1.136The analysis included study center as a stratification variable.
SecondarySubjective 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.

Time frame:
Week 26
Reported as:
Mean · units on a scale
Subjective Patient Assessment of Treatment at Week 26
units on a scaleIA-SAIA-BioHA
Subjective Patient Assessment of Treatment at Week 262.71 ± 1.0962.70 ± 1.115
Statistical analysis
  • IA-SA vs IA-BioHA · Cochran-Mantel-Haenszel · p = 0.887 (For secondary outcome measures, fixed-sequence testing was used in a sequentially rejective fashion. The a priori threshold for statistical significance was p \<0.05.)The analysis included study center as a stratification variable.
SecondaryNumber 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.

Time frame:
Day 1 to week 26
Reported as:
Mean · tablets

No measurements were reported for this outcome.

SecondaryChange 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.

Time frame:
Day 0 (baseline), Week 26
Reported as:
Least squares mean · units on a scale
Change From Baseline in Patient Global Assessment at Week 26
units on a scaleIA-SAIA-BioHA
Change From Baseline in Patient Global Assessment at Week 26-27.41 ± 1.83-23.41 ± 1.85
Statistical analysis
  • IA-SA vs IA-BioHA · Mixed Models Repeated Measures ANCOVA · p = 0.116 (For secondary outcome measures, fixed-sequence testing was used in a sequentially rejective fashion. The a priori threshold for statistical significance was p \<0.05.) · Adjusted mean difference: 4.00 · 95% CI -0.99 to 8.98The analysis included baseline score as a covariate and study center as a stratification variable.
SecondaryPercentage 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.

Time frame:
Day 0 (baseline), week 26
Reported as:
Number · percentage of participants
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
percentage of participantsIA-SAIA-BioHA
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 2670.062.2
Statistical analysis
  • IA-SA vs IA-BioHA · Regression, Logistic · p = 0.081 (For secondary outcome measures, fixed-sequence testing was used in a sequentially rejective fashion. The a priori threshold for statistical significance was p \<0.05.) · Odds ratio (or): 0.710 · 95% CI 0.483 to 1.044The analysis included study center as a stratification variable.

Adverse events

Collected over Double-blind period is day 1 to week 26. The open-label period is week 27 to week 52.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
IA-SA: Double-blind Period—6/298 (2%)25/298 (8.4%)
IA-BioHA: Double-blind Period—13/298 (4.4%)29/298 (9.7%)
IA-BioHA: Open-label Period—12/454 (2.6%)32/454 (7%)
Most frequent serious events
Showing 10 of 34
Most frequent serious events
EventIA-SA: Double-blind PeriodIA-BioHA: Double-blind PeriodIA-BioHA: Open-label Period
Atrial fibrillationCardiac disorders2/2980/2980/454
BradycardiaCardiac disorders0/2981/2980/454
Cardiac failure congestiveCardiac disorders0/2981/2980/454
MyopericarditisCardiac disorders0/2981/2980/454
Angina pectorisCardiac disorders1/2980/2981/454
Urethral intrinsic sphincter deficiencyCongenital, familial and genetic disorders0/2981/2980/454
Chest painGeneral disorders0/2981/2980/454
DeathGeneral disorders0/2981/2980/454
Intraspinal abscessInfections and infestations0/2981/2980/454
PneumoniaInfections and infestations0/2981/2981/454
Most frequent other events
Most frequent other events
EventIA-SA: Double-blind PeriodIA-BioHA: Double-blind PeriodIA-BioHA: Open-label Period
ArthralgiaMusculoskeletal and connective tissue disorders25/29829/29832/454

Baseline characteristics

Age Continuous
Age Continuous(years)IA-SAIA-BioHATotal
Mean60.30 ± 11.18060.70 ± 10.22860.50 ± 10.708
Sex: Female, Male
Sex: Female, Male(Participants)IA-SAIA-BioHATotal
Female193168361
Male105130235
08

Study locations

34 sites
  • Apex Clinical Trials, LLC
    Homewood, Alabama, United States
  • Tucson Orthopaedic Institute
    Tucson, Arizona, United States
  • St. Joseph's Mercy Clinic
    Hot Springs, Arkansas, United States
  • Rx Medical Research of Arkansas, Inc
    Little Rock, Arkansas, United States
  • Southbay Pharma Research
    Buena Park, California, United States
  • Providence Clinical Research
    Burbank, California, United States
  • Triwest Research Associates
    La Mesa, California, United States
  • UCLA-Division of Rheumatology
    Los Angeles, California, United States
  • Investigational Site
    Santa Barbara, California, United States
  • Colorado Arthritis Center, PC
    Englewood, Colorado, United States
  • Front Range Clinical Research
    Wheatridge, Colorado, United States
  • New England Research Associates, LLC
    Trumball, Connecticut, United States
  • International Physicians Research
    Aventura, Florida, United States
  • Investigational Site
    Ft. Lauderdale, Florida, United States
  • Sunrise Medical Research
    Lauderdale Lakes, Florida, United States
  • Tri-County Orthopaedic Center
    Leesburg, Florida, United States
  • Clinical Research Center LLC
    Wellington, Florida, United States
  • National Pain Research Institute, LLC
    Winter Park, Florida, United States
  • Georgia Institute for Clinical Research
    Marietta, Georgia, United States
  • Pinnacle Orthopaedics and Sports Medicine
    Marietta, Georgia, United States
  • Lee Research Institute
    Shawnee, Kansas, United States
  • Professional Research Network of Kansas
    Wichita, Kansas, United States
  • New Jersey Physicians, LLC
    Passaic, New Jersey, United States
  • Research Department, Bone & Joint Hospital at St. Anthony
    Oklahoma City, Oklahoma, United States
  • Omega Medical Research
    Warwick, Rhode Island, United States
  • Palmetto Medical Research
    Mt. Pleasant, South Carolina, United States
  • Palmetto Clinical Trial Services, LLC
    Simpsonville, South Carolina, United States
  • Black Hills Orthopedic & Spine Center
    Rapid City, South Dakota, United States
  • Holston Medical Group
    Kingsport, Tennessee, United States
  • McKenzie Medical Center
    McKenzie, Tennessee, United States
  • Texas Orthopedic Specialists, PA
    Grapevine, Texas, United States
  • Memorial Bone & Joint Research Foundation
    Houston, Texas, United States
  • Discovery Clinical Trials (DCT) - Stone Oak, LLC
    San Antonio, Texas, United States
  • Northwest Clinical Research Center
    Bellevue, Washington, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 15, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00988091
Lead sponsor
Ferring Pharmaceuticals
Responsible party
Sponsor
First posted
Oct 1, 2009
Start date
Sep 2009
Primary completion
Oct 2010
Completion
Apr 2011
Results posted
Jun 4, 2012
Last update
Jun 15, 2012

Study contacts

Clinical Development Support
study director · Ferring Pharmaceuticals

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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