Effect of ZILRETTA Versus CELESTONE on Quality of Life, Pain, Neuromuscular Function, and Physical Performance

NCT05058209 | Completed Phase 4 FDA Drug

• 1 other identifier: 1657878
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the pre, post, and follow up effects of a single ZILRETTA knee injection vs a single CELESTONE SOLUSPAN knee injection on physiological measure of self-reported quality of life, pain, physical function, and physical performance in individuals with osteoarthritis (OA) knee pain. The Primary Investigator (PI) will recruit 20 symptomatic knee OA patients for this study. Patients will be randomized into one of two treatment arms, Arm 1 (ZILRETTA injection) or Arm 2 (CELESTONE SOLUSPAN injection). Patients in Arm 1 will receive a single 5 mL IV injection of 32 mg ZILRETTA into the affected knee joint. Patients in Arm 2 will receive a 5ml IV injection of 6mg/ml CELESTONE SOLUSPAN into the affected knee joint. Each study arm will include 10 patients. All data will be collected prior to injection (baseline), as well as at 6-week (post 1) and 12-week follow-ups (post 2). Patients will blinded to treatment arm until after they complete their 12-week follow up.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (18)

• OARSI - 30-second Chair Stand

  The maximum number of chair stand repetitions possible in a 30 second period (2-4).

  Baseline (removed due to COVID)

• OARSI - 30-second Chair Stand

  The maximum number of chair stand repetitions possible in a 30 second period (2-4).

  6 week (removed due to COVID)

• OARSI - 30-second chair standing test

  The maximum number of chair stand repetitions possible in a 30 second period (2-4).

  12 week (removed due to COVID)

• OARSI - 40m Fast Paced Walk

  A fast-paced walking test that is timed over 4 x 10m (33 ft) for a total 40 m (132 ft) (2).

  Baseline (removed due to COVID)

• OARSI - 40m Fast Paced Walk

  A fast-paced walking test that is timed over 4 x 10m (33 ft) for a total 40 m (132 ft) (2).

  6 week (removed due to COVID)

• OARSI - 40m Fast Paced Walk

  A fast-paced walking test that is timed over 4 x 10m (33 ft) for a total 40 m (132 ft) (2).

  12 week (removed due to COVID)

• OARSI - stair ascent

  The time (in seconds) it takes to ascend and descend a flight of stairs (2-6). The number of stairs will depend on individual environmental situations. Where possible, the 9-step stair test with 20cm (8 inch) step height and handrail is recommended.

  Baseline (removed due to COVID)

• OARSI - stair ascent

  The time (in seconds) it takes to ascend and descend a flight of stairs (2-6). The number of stairs will depend on individual environmental situations. Where possible, the 9-step stair test with 20cm (8 inch) step height and handrail is recommended.

  6 week (removed due to COVID)

• OARSI - stair ascent

  The time (in seconds) it takes to ascend and descend a flight of stairs (2-6). The number of stairs will depend on individual environmental situations. Where possible, the 9-step stair test with 20cm (8 inch) step height and handrail is recommended.

  12 week (removed due to COVID)

• KOOS-PS (Physical Function Shortform)

  Scoring: Never/none=0, Monthly/mild=1, Weekly/moderate=2, Daily/severe=3, Always/extreme=4. Calculate the mean score for the 11 items, and divide by the maximum possible score for each item (i.e. 4). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard. Please use the formula provided below. 100 - \[(mean score PF1-PF11)/4 \*100\]

  6 week

• KOOS-PS (Physical Function Shortform)

  Scoring: Never/none=0, Monthly/mild=1, Weekly/moderate=2, Daily/severe=3, Always/extreme=4. Calculate the mean score for the 11 items, and divide by the maximum possible score for each item (i.e. 4). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard. Please use the formula provided below. 100 - \[(mean score PF1-PF11)/4 \*100\]

  Baseline

• KOOS-PS (Physical Function Shortform)

  Scoring: Never/none=0, Monthly/mild=1, Weekly/moderate=2, Daily/severe=3, Always/extreme=4. Calculate the mean score for the 11 items, and divide by the maximum possible score for each item (i.e. 4). Traditionally in orthopedics, 100 indicates no problems and 0 indicates extreme problems. The normalized score is transformed to meet this standard. Please use the formula provided below. 100 - \[(mean score PF1-PF11)/4 \*100\]

  12 week

• KOOS-Quality of life subscale (QoL)

  The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.

  Baseline

• KOOS-Quality of life subscale (QoL)

  The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.

  6 week

• KOOS-Quality of life subscale (QoL)

  The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as common in orthopaedic scales and generic measures. Scores between 0 and 100 represent the percentage of total possible score achieved.

  12 week

• Numerical Rating Scale (NRS)

  patient to rate their pain on a defined scale. For example, 0-10 where 0 is no pain and 10 is the worst pain imaginable

  Baseline

• Numerical Rating Scale (NRS)

  patient to rate their pain on a defined scale. For example, 0-10 where 0 is no pain and 10 is the worst pain imaginable

  6 week

• Numerical Rating Scale (NRS)

  patient to rate their pain on a defined scale. For example, 0-10 where 0 is no pain and 10 is the worst pain imaginable

  12 week

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

Triamcinolone acetonide extended-release injectable suspension. Single intra-articular extended-release injection of triamcinolone acetonide, to deliver 32 mg (5 mL). For intra-articular use only and should not be administered by the following routes: epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, subcutaneous.

Drug: Triamcinolone acetonide extended-release injectable suspension

Arm 2

ACTIVE COMPARATOR

Betamethasone sodium phosphate and betamethasone acetate Injectable Suspension, USP 6 mg per mL, 3 mg per milliliter betamethasone, as betamethasone sodium phosphate, and 3 mg per milliliter betamethasone acetate. When oral therapy is not feasible, the Injectable Suspension is indicated for intramuscular use only.

Drug: Betamethasone sodium phosphate and betamethasone acetate Injectable Suspension

Interventions

Triamcinolone acetonide extended-release injectable suspension DRUG

Zilretta (Triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of pain due to knee OA. The most commonly reported adverse reactions (incidence ≥1%) in clinical studies included sinusitis (2%), cough (2%), contusions (2%) and joint swelling (3%). For additional details, please see Package Insert (http://www.zilrettalabel.com/PI.pdf). The website for Zilretta additionally lists: joint pain, headache, back pain, sore throat and runny nose, and bruising as common side effects of receiving a Zilretta injection.

Also known as: Zilretta

Arm 1

Betamethasone sodium phosphate and betamethasone acetate Injectable Suspension DRUG

Celestone (betamethasone sodium phosphate and betamethasone acetate Injectable Suspension, USP 6 mg per mL) is indicated as an intra-articular injection for the management of chronic or long-term inflammation associated with multiple conditions including severe allergies, dermatological diseases, endocrine disorders, gastrointestinal diseases, hematologic disorders, neoplastic diseases, nervous system disorders, ophthalmologic diseases, renal diseases, respiratory diseases and rheumatic disorders, and others that may not be listed. Celestone Soluspan is available in generic form. The most commonly reported adverse reactions include acne, increased hunger, and weight gain.

Also known as: Celestone

Arm 2

Eligibility Criteria

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

You may qualify if:

• Men and women age 18 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)
• Ambulatory
• Willing and able to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ROC Foundation: lead

Study Sites (1)

Reno Orthopedic Center

Reno, Nevada, 89503, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Triamcinolone; betamethasone sodium phosphate; Betamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienetriols

Study Officials

• Sara C DePaoli

  ROC Foundation

  STUDY DIRECTOR

• Timothy J Bray, MD

  ROC Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Investigator and participant were blinded to study arm until the end of thier final visit/phone call. Medical assistant prepping injections and CCRC were not blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized and Controlled Blinded Clinical Trial

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 27, 2021
• Study Start: November 30, 2020
• Primary Completion: April 28, 2021
• Study Completion: April 28, 2021
• Last Updated: September 27, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)