Effect of Zilretta Injection

NCT04261049 | Completed Phase 1 FDA Drug

• 1 other identifier: 19-3562
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the pre-post effects of a single ZILRETTA knee injection on physiological measures of self-reported pain and disability, physical performance, and physical activity in individuals with knee osteoarthritis (OA). The investigators will recruit 35 symptomatic knee OA patients for this study. All data will be collected prior to injection (baseline), as well as at 4 (post 1) and 8-week follow-ups (post 2).

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (11)

• Percentage Change in Mean Maximal Quadriceps Strength as Measured by the Maximal Isometric Voluntary Contractions Normalized to Body Weight from Baseline to the 8-week follow-up.

  Quadriceps strength was measured in Newton Meters normalized to body weight of the individuals. Strength was assessed in 90 degrees of knee flexion.

  Baseline and 8-week follow-up

• Percentage Change in Mean Voluntary Quadriceps Activation as Measured by the Central Activation Ratio Expressed as a Percent of Full Activation from Baseline to the 8-week follow-up.

  The investigators assessed voluntary quadriceps central activation ratio as a representative variable of lower extremity neuromuscular activation using the supra imposition technique. Quadriceps central activation ratio has been demonstrated to be significantly decreased in knee osteoarthritis (OA) compared to healthy, matched controls, and the investigators have reported acceptable measurement reliability (ICC2,k = 0.85)

  Baseline and 8-week follow-up

• Percentage Change in Mean Knee Flexion Angle During Walking Gait Measured in Degrees of Knee Flexion from Baseline to the 8-week follow-up.

  The peak Knee Flexion Angle was calculated using using inverse dynamics calculations in the first 50% of the stance phase of gait and during self selected gait speed.

  Baseline and 8-week follow-up

• Percentage Change in Mean Internal Knee Extension Moment During Walking Gait Measured in Nm/ Body Weight*m from Baseline to the 8-week follow-up.

  The peak internal knee extension moment was calculated using using inverse dynamics calculations in the first 50% of the stance phase of gait and normalized to the Body Weight\* height (m) of the individual during self selected gait speed.

  Baseline and 8-week follow-up

• Percentage Change in Mean of Self-reported Disability Score as Measured by the Western Ontario and McMasters Universities Index from Baseline to the 8-week follow-up.

  The Western Ontario and McMasters Universities Index is reliable and valid measure of self reported disability. The physical function consists of 17 items and asks about the magnitude of difficulty when ascending and descending stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on and taking off socks, rising from bed, lying in bed, getting in and out of the bath, sitting, getting on and off the toilet, completing heavy household duties, and completing light household duties. Each item is presented in a 5 point Likert-type format and uses the following descriptors for possible answer choices none, mild moderate, severe, and extreme. Each descriptor corresponds to an ordinal scale of 0-4. The scores are summed for the items in each subscale, with total possible ranges as 0-68. Higher scores on the WOMAC indicate greater amounts of functional limitations.

  Baseline and 8-week follow-up

• Percentage Change in mean of self-reported Disability Score as Measured by the Knee Injury and Osteoarthritis Outcome Score from Baseline to the 8-week follow-up.

  The Knee Injury and Osteoarthritis Outcomes Score (KOOS) consists of five subscales: Pain (9 items), Symptoms (7 items), Function in Activities of Daily Living (17 items), Function in Sport and Recreation (5 items) and Knee Related Quality of Life (4 items). Each item is presented in a 5 point Likert-type format that ranges from 0 (no problems) to 4 (extreme problems). Totals from each subscale are transformed to a 0-100 score. Lower scores on the KOOS indicate greater amounts of functional limitations.

  Baseline and 8-week follow-up

• Percentage Change in Physical Activity Scale for the Elderly from baseline to the 8-week follow-up.

  Physical Activity Scale for the Elderly (PASE) scores are calculated from weights and frequency values for each of 12 types of activity. Responses to the first question about sitting activities are not scored. The scale is continuous with higher scores indicating greater physical activity.

  Baseline and 8-week follow-up

• Percentage Change in 30-s chair-stand test from Baseline to the 8-week follow-up.

  The number of times that an individual can sit and stand in 30 seconds.

  Baseline and 8-week follow-up

• Percentage Change in 20 meter fast-paced walk test from Baseline to the 8-week follow-up.

  The investigators will time the amount of seconds it takes to walk 20 meters.

  Baseline and 8-week follow-up

• Percentage Change in Stair-climb test from Baseline to the 8-week follow-up.

  The investigators will time the amount of seconds it takes to walk up and down a flight of stairs.

  Baseline and 8-week follow-up

• The percentage change in steps per day from Baseline to the 8-week follow-up.

  Physical activity will be measured in the form of steps per day using an ActiGraph accelerometer. Participants will wear the ActiGraph for 7 days following each testing session.

  Baseline and 8-week follow-up

Study Arms (1)

ZILRETTA Injection

EXPERIMENTAL

All patients upon enrolling in the study will receive a single 5 mL injection of 32 mg ZILRETTA into the affected knee joint.

Drug: Triamcinolone Acetonide Extended-Release Injectable Suspension

Interventions

Triamcinolone Acetonide Extended-Release Injectable Suspension DRUG

A single ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) intra-articular knee injection.

Also known as: Zilretta Injectable Product

ZILRETTA Injection

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between the ages of 40 and 75 years old who:
• Exhibit symptomatic knee OA, defined as a normalized WOMAC function subscale score \>31(out of 100 points, indicating highest degree of dysfunction)
• Have radiographic evidence of tibiofemoral OA (2-4 on the Kellgren-Lawrence scale)
• Provide written informed consent and the ability to comply with the requirements of the study.
• Be willing to abstain from use of the following protocol-restricted medications during the study:
• Corticosteroid injections into the knee or any lower extremity joint will be restricted for 3 months prior to the screening visit (based on the drug half-life) and throughout the entirety of the study period including the 8-week follow-up test. Information about when the latest corticosteroid injection occurred for each participant prior to screening in order to determine when each participant can attend the screening visit.
• Hyaluronic acid injections into the knee or any lower extremity joint will be restricted for 6 months prior to the screening visit (based on the drug half-life) and throughout the entirety of the study period including the 8-week follow-up test. Information about when the latest hyaluronic acid injection occurred for each participant prior to screening in order to determine when each participant can attend the screening visit.
• Prescription Depressants (Examples: opiates and opioids, barbiturates, tranquilizers and benzodiazepines) will be restricted 4-weeks prior to screening and throughout the study period as these medications may affect the neuromuscular function.
• Prescription Stimulants (Example: amphetamines) will be restricted 4-weeks prior to screening and throughout the study period as these medications may affect the neuromuscular function
• Non-steroidal anti-inflammatory drugs (NSAIDs) will be restricted 24 hours prior to screening or follow-up testing sessions. NSAID use will be tracked and patients instructed not to change their NSAIDs usage during the 8-weeks of the study.
• Acetaminophen will be restricted 24 hours prior to screening or follow-up testing sessions. Acetaminophen use will be tracked and patients instructed not to change their Acetaminophen usage during the 8-weeks of the study.

You may not qualify if:

• Potential participants meeting any of the following criteria (based on the electronic medical record or in laboratory screening) will be excluded if they:
• Are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product
• Have other intra-articular investigational drug/biologic use in the previous 6-months
• Have been diagnosed with a cardiovascular condition restricting exercise
• Have had a corticosteroid injection in the involved knee in the previous 3-months or hyaluronic acid injection in the involved knee in the previous 6-months
• Have a pacemaker
• Have a neurodegenerative condition
• Have rheumatoid arthritis
• Have diabetes
• Have cancer
• Have a neural sensory dysfunction over the knee
• Have a body mass index (BMI) over 35
• Have a history of lower extremity orthopaedic surgery in the past year
• Have a history of a traumatic knee injury in the past 6 months
• Have any history of total knee arthroplasty in either extremity

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Pacira Pharmaceuticals, Inc: collaborator

Study Sites (1)

MOTION Science Institute

Chapel Hill, North Carolina, 27516, United States

Location

Related Publications (30)

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MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Brian Pietrosimone, PhD, ATC

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: August 1, 2020
• Primary Completion: January 10, 2022
• Study Completion: January 10, 2022
• Last Updated: May 20, 2022

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)