The Effect of Intra-articular Bilateral Knee Injections of Zilretta on Performance Measures in Adults With Knee OA

Sponsor
University of Kansas Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT03895840
Collaborator
(none)
70
1
1
37.5
1.9

Study Details

Study Description

Brief Summary

This study will be an open-label trial to determine the functional effects of bilateral IA injections of Zilretta into knee joints of 70 subjects with bilateral KL grade 2-4 symptomatic knee osteoarthritis (OA). Measurement and evaluation of outcomes at baseline, 6, 12 and 24 weeks will allow assessment of short and long-term effects, consistent with Osteoarthritis Research Society International (OARSI) and Outcome Measures in Rheumatology (OMERACT) recommendations.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The primary aim of the proposed study is to demonstrate the effect of IA injection of Zilretta on physical performance measures in adults with bilateral knee OA. The primary study endpoint will be the change in OARSI recommended physical performance tests (30-second chair standing test, 40m fast-paced walking test, stair ascent) 12 weeks after treatment.

The secondary outcome will be the change in Knee Injury and Osteoarthritis Outcome Score (KOOS-PS) patient-reported physical function short form.

The tertiary outcomes will be the change in KOOS-Quality of life subscale (QoL) and Numerical Rating Scale (NRS) for pain. All outcomes will be assessed at 6- and 24-week follow-up as well to define the course and trajectory of effects.

Specific Aim 1: To determine the extent to which intra-articular (IA) injection of Zilretta in patients with bilateral knee OA improves physical performance (OARSI recommended physical performance measures).

Primary Hypothesis 1: Bilateral knee intra-articular injection of Zilretta results in improved physical performance detectable at 6 weeks, 12 weeks (primary), and 24 weeks.

Specific Aim 2: To determine the extent to which IA injection of Zilretta in patients with bilateral knee OA improves physical function (KOOS-PF).

Hypothesis 2: Bilateral knee IA injection of Zilretta results in improved patient-reported physical function (KOOS-PS) at 6 weeks,12 weeks (primary), and 24 weeks.

Specific Aim 3: To determine the extent to which bilateral knee IA injection of Zilretta in patients with bilateral knee OA improves quality of life (KOOS-QoL).

Hypothesis 3: Intra-articular (IA) bilateral knee injection of Zilretta in patients with bilateral knee osteoarthritis results in improved quality of life (KOOS-QoL) detectable at 6 weeks, 12 weeks (primary), and 24 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
70 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This will be an open-label study to determine the functional effects of IA injection of Zilretta into bilateral knees of 70 subjects with KL grade 2-4 symptomatic knee OA. Measurement of OARSI recommended physical performance measures, patient-reported physical function, quality of life and pain at baseline, 6, 12 and 24 weeks will allow assessment of short and long-term effects, consistent with OARSI and OMERACT recommendationsThis will be an open-label study to determine the functional effects of IA injection of Zilretta into bilateral knees of 70 subjects with KL grade 2-4 symptomatic knee OA. Measurement of OARSI recommended physical performance measures, patient-reported physical function, quality of life and pain at baseline, 6, 12 and 24 weeks will allow assessment of short and long-term effects, consistent with OARSI and OMERACT recommendations
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Effect of Intra-articular Bilateral Knee Injections of Zilretta on Osteoarthritis Research Society International (OARSI) Recommended Physical Performance Measures in Adults With Knee Osteoarthritis
Actual Study Start Date :
Mar 19, 2018
Actual Primary Completion Date :
May 3, 2021
Actual Study Completion Date :
May 3, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intra-articular Zilretta injection

32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines

Drug: Zilretta
Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
Other Names:
  • FX006
  • Triamcinolone acetonide extended-release
  • Outcome Measures

    Primary Outcome Measures

    1. 30 Second Chair Standing Test [12 weeks]

      The 30 second Chair Standing Test is one of three Osteoarthritis Research Society International (OARSI) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.In this test, the subject will stand up completely from the sitting position so hips and knees are fully extended, then completely back in the seated position. This will be repeated for 30 seconds and the total number of chair stands will be recorded (up and down equals one stand).

    2. 40m Fast Paced Walking Test (40m FPWT) [12 weeks]

      The 40-meter fast paced walk test is one of the three Osteoarthritis Research Society International recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The subjects will be timed to complete a 40 m track course.

    3. Timed Stair Climb [12 weeks]

      The stair climb test is one of the three Osteoarthritis Research Society International recommended minimal core set of performance-based outcome measures in OA research and clinical practice. The subject will be timed while ascending and descending 9 steps of stairs.

    Secondary Outcome Measures

    1. KOOS-PS (Knee Osteoarthritis Outcome Score - Physical Function Short Form) [12 weeks]

      KOOS-Physical Function (KOOS-PS) Short Form is a parsimonious measure of physical function derived from the KOOS, which is a self-reported outcome score. The KOOS-Physical Function Short Form ranges from 0 to 100 where higher values represents a worse outcome.

    Other Outcome Measures

    1. KOOS-QoL (Knee Osteoarthritis Outcome Score - Quality of Life) [12 weeks]

      KOOS-QoL a self-reported measure consisting of 4 questions assessing quality of life, which is part of the five patient-relevant subscales of KOOS.The sub scale ranges from 0 to 100 where higher values represents a better outcome

    2. NRS for Pain [12 weeks]

      The Numeric Rating Scale for Pain (NRS for Pain) is a measure of pain intensity. The subject will rate their knee pain bilaterally on a scale from no pain (0) to worst pain imaginable (10).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Men and women age 30 years or older with symptomatic bilateral knee OA

    • Symptomatic knee OA will be defined as the presence of a definite osteophyte or joint space narrowing (KL Grade ≥2) on posteroanterior (PA) fixed flexion knee radiographs in subjects limited by bilateral pain rated on a Numerical Rating Scale as ≥ 4/10 on more than half of the days over the past month. Radiographic change must be visible at standard image size, irrespective of capability to detect more subtle changes through digital enhancement.

    • Bilateral knee symptoms for ≥ 3 months prior to screening

    • Has undergone at least one prior conservative osteoarthritis treatment (e.g. Physical therapy, analgesics)

    • Body Mass Index ≤ 41 kg/m2

    • Ambulatory

    • Willing and able to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.

    • Willingness to abstain from the use of protocol-restricted medications during the study after signing informed consent and also willing to abstain from use of all analgesics other than acetaminophen 1 week prior to beginning of treatment.

    Exclusion Criteria:
    • Current consumption of more than 14 alcoholic drinks per week

    • Clinical signs and symptoms of active knee infection or crystal disease of either knee within 1 month of screening

    • Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; HIV, viral hepatitis; chondrocalcinosis, Paget's disease, or villonodular synovitis

    • Diagnosed with leukemia, known presence of metastatic malignant cells, or ongoing or planned chemotherapeutic treatment.

    • A gout attack in the past 2 years.

    • Diseases of the spine, hip or other lower extremity joints judged by the investigator to be contributing to the pain in either knee (i.e. sciatica, nerve pain, hip OA). Note: Patients with hip replacement in either hip may be enrolled provided there is sufficient pain relief after hip replacement that analgesics are not required.

    • Untreated symptomatic injury of either knee (e.g., acute traumatic injury, anterior cruciate ligament injury, clinically symptomatic meniscus injury characterized by a mechanical issue such as locking or catching).

    • Uncontrolled diabetes (HbA1c >7.2)

    • Women who report pregnancy or childbearing potential and not using acceptable contraceptive measures (oral contraceptive, long acting reversible contraceptive therapy) (due to the potential for change in body mass and distribution to alter knee symptoms over the period of follow-up).

    • Presence of surgical hardware or other foreign body intended to treat arthritis or cartilage-related pathology in either knee.

    • Arthroscopy or open surgery of either knee within 6 months of screening.

    • Planned/anticipated surgery of either knee during the study period.

    • Use of systemic immunosuppressant within 6 weeks of screening.

    • Oral corticosteroids (investigational or marketed) within 2 weeks of screening (unless on chronic stable dose for >3 months).

    • IA corticosteroid (investigational or marketed) in either knee within 3 months of screening.

    • IV or IM (Intramuscular) Corticosteroid injection (investigational or marketed) within 3 months of screening.

    • Any other IA drug/biologic use within 6 months of screening or 5 half-lives (whichever is longer) (e.g., hyaluronic acid, platelet-rich plasma (PRP) injection, stem cells, prolotherapy and amniotic fluid injection).

    • Any documented clinically significant degree of cognitive impairment or other condition, finding, or psychiatric illness at screening which, in the opinion of the investigator, could compromise subject safety.

    • Any condition other than OA of the knee which, in the opinion of the investigator, affects the ability to ambulate to a sufficient degree to interfere with the assessment of the safety and treatment effects of the study injection.

    • Participated in any interventional drug or device trial within 30 days prior to screening or concurrent participation in another research study that could complicate interpretation of the study findings.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Kansas Medical Center Kansas City Kansas United States 66160

    Sponsors and Collaborators

    • University of Kansas Medical Center

    Investigators

    • Principal Investigator: Neil A Segal, MD, University of Kansas Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    University of Kansas Medical Center
    ClinicalTrials.gov Identifier:
    NCT03895840
    Other Study ID Numbers:
    • STUDY00142926
    First Posted:
    Mar 29, 2019
    Last Update Posted:
    May 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Period Title: Overall Study
    STARTED 70
    6-Week Follow-Up 70
    12-Week Follow-Up 65
    24-Week Follow-Up 49
    COMPLETED 49
    NOT COMPLETED 21

    Baseline Characteristics

    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Overall Participants 70
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.0
    (11.7)
    Sex: Female, Male (Count of Participants)
    Female
    43
    61.4%
    Male
    27
    38.6%
    Race and Ethnicity Not Collected (Count of Participants)
    Region of Enrollment (participants) [Number]
    United States
    70
    100%
    BMI (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    31.8
    (5.7)
    Chair Stand (#) (stands) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [stands]
    7.7
    (3.6)
    Stair Climb (sec) (seconds) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [seconds]
    22.1
    (28.9)
    40m Walk Time (sec) (seconds) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [seconds]
    37.3
    (26.0)
    Physical Function (KOOS) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    50.9
    (11.3)
    Quality of Life (KOOS) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    27.4
    (16.8)

    Outcome Measures

    1. Primary Outcome
    Title 30 Second Chair Standing Test
    Description The 30 second Chair Standing Test is one of three Osteoarthritis Research Society International (OARSI) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.In this test, the subject will stand up completely from the sitting position so hips and knees are fully extended, then completely back in the seated position. This will be repeated for 30 seconds and the total number of chair stands will be recorded (up and down equals one stand).
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [stands]
    9.5
    (0.5)
    2. Primary Outcome
    Title 40m Fast Paced Walking Test (40m FPWT)
    Description The 40-meter fast paced walk test is one of the three Osteoarthritis Research Society International recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The subjects will be timed to complete a 40 m track course.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [seconds]
    35.9
    (2.6)
    3. Primary Outcome
    Title Timed Stair Climb
    Description The stair climb test is one of the three Osteoarthritis Research Society International recommended minimal core set of performance-based outcome measures in OA research and clinical practice. The subject will be timed while ascending and descending 9 steps of stairs.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [seconds]
    15.0
    (1.4)
    4. Secondary Outcome
    Title KOOS-PS (Knee Osteoarthritis Outcome Score - Physical Function Short Form)
    Description KOOS-Physical Function (KOOS-PS) Short Form is a parsimonious measure of physical function derived from the KOOS, which is a self-reported outcome score. The KOOS-Physical Function Short Form ranges from 0 to 100 where higher values represents a worse outcome.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [score on a scale]
    70.0
    (2.1)
    5. Other Pre-specified Outcome
    Title KOOS-QoL (Knee Osteoarthritis Outcome Score - Quality of Life)
    Description KOOS-QoL a self-reported measure consisting of 4 questions assessing quality of life, which is part of the five patient-relevant subscales of KOOS.The sub scale ranges from 0 to 100 where higher values represents a better outcome
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [score on a scale]
    51.9
    (3.4)
    6. Other Pre-specified Outcome
    Title NRS for Pain
    Description The Numeric Rating Scale for Pain (NRS for Pain) is a measure of pain intensity. The subject will rate their knee pain bilaterally on a scale from no pain (0) to worst pain imaginable (10).
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    Measure Participants 65
    Least Squares Mean (Standard Error) [units on a scale]
    3.3
    (0.3)

    Adverse Events

    Time Frame 24 Weeks
    Adverse Event Reporting Description
    Arm/Group Title Intra-articular Zilretta Injection
    Arm/Group Description 32 mg Zilretta in a 5ml diluent for each knee, per manufacturer guidelines Zilretta: Zilretta (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee osteoarthritis.
    All Cause Mortality
    Intra-articular Zilretta Injection
    Affected / at Risk (%) # Events
    Total 0/70 (0%)
    Serious Adverse Events
    Intra-articular Zilretta Injection
    Affected / at Risk (%) # Events
    Total 0/70 (0%)
    Other (Not Including Serious) Adverse Events
    Intra-articular Zilretta Injection
    Affected / at Risk (%) # Events
    Total 34/70 (48.6%)
    Blood and lymphatic system disorders
    Bruising 3/70 (4.3%) 3
    Epistaxis 1/70 (1.4%) 1
    Hematuria 1/70 (1.4%) 1
    Swelling 2/70 (2.9%) 2
    Ear and labyrinth disorders
    Otitis media 1/70 (1.4%) 1
    Endocrine disorders
    Hyperglycemia 1/70 (1.4%) 1
    General disorders
    Fall 8/70 (11.4%) 8
    Flu-like symptoms 1/70 (1.4%) 1
    headache 2/70 (2.9%) 2
    Immune system disorders
    Allergic rhinitis 1/70 (1.4%) 1
    Musculoskeletal and connective tissue disorders
    arthralgia 7/70 (10%) 7
    Renal and urinary disorders
    URI 4/70 (5.7%) 4
    Respiratory, thoracic and mediastinal disorders
    Rhinorrea 1/70 (1.4%) 1
    Skin and subcutaneous tissue disorders
    Blister 1/70 (1.4%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Neil Segal, MD
    Organization University of Kansas Medical Center
    Phone 9135740961
    Email segal-research@kumc.edu
    Responsible Party:
    University of Kansas Medical Center
    ClinicalTrials.gov Identifier:
    NCT03895840
    Other Study ID Numbers:
    • STUDY00142926
    First Posted:
    Mar 29, 2019
    Last Update Posted:
    May 5, 2022
    Last Verified:
    Apr 1, 2022