Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in the Context of Type II Diabetes

NCT06478186 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: STUDY00160230006-C-201
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2 Randomized Study to Evaluate the Effects of triamcinolone acetonide extended-release (TA-ER; Zilretta) vs. triamcinolone acetonide immediate-release (TA-IR; Kenalog) on Blood Glucose Levels in Diabetic Subjects with Knee Osteoarthritis. Subjects should have Type 2 Diabetes Mellitus (T2DM) with HbA1C ≤9 that is managed without insulin and have been diagnosed with symptomatic unilateral or bilateral osteoarthritis (OA) of the knee, based on clinical and radiological criteria (if bilateral, then a target knee will be selected).Total study duration for individual subject will be about 4 months, which includes 3 weeks of Screening period, 10 days of pretreatment phase, treatment day, and 12 weeks of post-treatment period.

Conditions

Osteoarthritis, Knee; Diabetes Mellitus, Type 2

Keywords

Zilretta; Kenalog

Outcome Measures

Primary Outcomes (1)

• Percent of time spent with blood glucose >180 mg/dL

  To assess continuous glucose monitoring (CGM) patterns for Time Above Range (TAR) levels of the upper limit of the recommended target range (glucose levels \>180 mg/dL) from Baseline to 72 hours following a single IA injection of 32 mg of ZILRETTA relative to 40 mg of TA-IR.

  The primary outcome will be measured up to 72 hours after treatment by a sensor automatically uploading the data

Secondary Outcomes (7)

• Area under the curve (AUC) for cortisol levels

  From baseline until the end-of-study (Day 85).

• Percentage of time spent with blood glucose above >180 mg/dL

  From baseline throughout 10 days follow-up.

• Number of blood glucose peaks ≥250 mg/dL

  From baseline throughout 10 days follow-up

• Change in 40m walk time

  Between baseline and 12 weeks.

• Change in stair climb time

  Between baseline and 12 weeks.

Other Outcomes (5)

• Change in worst daily knee pain intensity

  From baseline to Weeks 6 and 12

• Change in Average Daily Pain

  From baseline to each follow-up week from 1 to 12 weeks after treatment

• Effect of hyperglycemia on fatigue

  From baseline to time periods of 0 to 24 hours (Days 1-2); 0 to 48 hours (Days 1- 3); and 0 to 72 hours (Days 1-4), for ZILRETTA relative to TCA-IR. Diabetes Symptom Checklist - Revised (DSC-R) is scored from a low of 1 to a high of 5.

Study Arms (2)

TA-ER

ACTIVE COMPARATOR

Name: ZILRETTA (triamcinolone acetonide extended-release injectable suspension; TA-ER) Active ingredient: Extended-release formulation of TA in 75:25 poly (lactic-co-glycolic) acid (PLGA) microspheres Dosage: Nominal 32 mg TA, intra-articular (IA) injection, administered as a 5 mL injection Mode of Administration: IA Knee Injection

Drug: triamcinolone acetonide extended-release injectable suspension; TCA-ER

TA-IR

ACTIVE COMPARATOR

Name: Kenalog®-40 (triamcinolone acetonide injectable suspension) Active Ingredient: Triamcinolone Acetonide- Immediate Release (TA-IR) Dosage: 40 mg/mL, IA, administered as a 1 mL Injection: TA-IR Mode of Administration: IA Knee Injection

Drug: Triamcinolone Acetonide- Immediate Release;TCA-IR

Interventions

triamcinolone acetonide extended-release injectable suspension; TCA-ER DRUG

Mode of Administration: IA Knee Injection Nominal 32 mg TCA, intra-articular (IA) injection, administered as a 5 mL injection

TA-ER

Triamcinolone Acetonide- Immediate Release;TCA-IR DRUG

Mode of Administration: IA Knee Injection Triamcinolone Acetonide- Immediate Release (TCA-IR)

TA-IR

Eligibility Criteria

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

You may qualify if:

• \. Written consent to participate in the study. 2. Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.
• \. Male or female ≥40 years of age. 4. Females with negative pregnancy test, who are not breastfeeding and have no intention to become pregnant during the time from screening through EOS.
• \. Type 2 DM for at least 1 year prior to Screening. 6. Currently being treated with injectable (except insulin) and/or oral antidiabetic agents with stable doses for at least 1 month prior to Screening.
• \. HbA1c 6.5-9% (in past 8 weeks). 8. Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2. (in past 8 weeks) 9. Triglycerides \<500 mg/dL (in past 8 weeks) 10. Painful symptoms associated with OA of the knee for ≥6 months prior to Screening (NRS of 4-9 during most of the 30 days prior to enrollment).
• \. Currently meets modified ACR criteria (clinical and radiological) for OA (Altman et al, 1986) as follows:
• Knee pain
• At least 1 of the following:
• Stiffness \<30 minutes
• Crepitus
• Osteophytes 12. Index knee pain more than 15 days over the last month (as reported by the subject).
• \. Kellgren-Lawrence Grade 2-4. 14. Willingness to wear a CGM device uninterrupted for 24 hours per day throughout the required time during the study and comply to the correct use requirements of CGM throughout the trial and perform self BG checks as directed.
• \. Adequate BG data collected during the pretreatment phase (Day -10 through Day -1) ≥70% data available.

You may not qualify if:

• Disease-related Criteria
• Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease.
• History of infection in the index knee joint.
• Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening.
• Presence of surgical hardware or other foreign body in the index knee.
• Unstable joint (such as a torn anterior cruciate ligament) within 12 months of Screening.
• Moderate or severe kidney, liver, or thyroid disease.
• Glaucoma.
• Active cancer. Previous or Concomitant Treatment-related Criteria
• IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening.
• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening.
• IV or intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening.
• Oral corticosteroids (investigational or marketed) within 1 month of Screening.
• Inhaled, intranasal, or topical corticosteroids (investigational or marketed) within 2 weeks of Screening.
• Any other IA investigational device, drug/biologic within 6 months of Screening or 5 half-lives (whichever is longer).

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Related Publications (13)

• Russell SJ, Sala R, Conaghan PG, Habib G, Vo Q, Manning R, Kivitz A, Davis Y, Lufkin J, Johnson JR, Kelley S, Bodick N. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018 Dec 1;57(12):2235-2241. doi: 10.1093/rheumatology/key265.

  PMID: 30203101 BACKGROUND

• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.

  PMID: 3741515 BACKGROUND

• Arbuckle RA, Humphrey L, Vardeva K, Arondekar B, Danten-Viala M, Scott JA, Snoek FJ. Psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R)--a measure of symptom distress. Value Health. 2009 Nov-Dec;12(8):1168-75. doi: 10.1111/j.1524-4733.2009.00571.x. Epub 2009 Jun 24.

  PMID: 19558371 BACKGROUND

• Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1589. doi: 10.1016/j.joca.2019.06.011. Epub 2019 Jul 3.

  PMID: 31278997 BACKGROUND

• Bashir MA, Ray R, Sarda P, Li S, Corbett S. Determination of a safe INR for joint injections in patients taking warfarin. Ann R Coll Surg Engl. 2015 Nov;97(8):589-91. doi: 10.1308/rcsann.2015.0044.

  PMID: 26492905 BACKGROUND

• Choudhry MN, Malik RA, Charalambous CP. Blood Glucose Levels Following Intra-Articular Steroid Injections in Patients with Diabetes: A Systematic Review. JBJS Rev. 2016 Mar 22;4(3):e5. doi: 10.2106/JBJS.RVW.O.00029.

  PMID: 27500431 BACKGROUND

• Derendorf H, Mollmann H, Gruner A, Haack D, Gyselby G. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther. 1986 Mar;39(3):313-7. doi: 10.1038/clpt.1986.45.

  PMID: 3948470 BACKGROUND

• Johnston PC, Lansang MC, Chatterjee S, Kennedy L. Intra-articular glucocorticoid injections and their effect on hypothalamic-pituitary-adrenal (HPA)-axis function. Endocrine. 2015 Mar;48(2):410-6. doi: 10.1007/s12020-014-0409-5. Epub 2014 Sep 3.

  PMID: 25182149 BACKGROUND

• Kompel AJ, Roemer FW, Murakami AM, Diaz LE, Crema MD, Guermazi A. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology. 2019 Dec;293(3):656-663. doi: 10.1148/radiol.2019190341. Epub 2019 Oct 15.

  PMID: 31617798 BACKGROUND

• Mader R, Lavi I, Luboshitzky R. Evaluation of the pituitary-adrenal axis function following single intraarticular injection of methylprednisolone. Arthritis Rheum. 2005 Mar;52(3):924-8. doi: 10.1002/art.20884.

  PMID: 15751089 BACKGROUND

• Patel J, Schneider BJ, Smith CC; Spine Intervention Society's Patient Safety Committee. Fact Finders for Patient Safety: Intra-Articular Corticosteroid Injections and Hyperglycemia. Pain Med. 2018 May 1;19(5):1091-1092. doi: 10.1093/pm/pnx303. No abstract available.

  PMID: 29741744 BACKGROUND

• Tamez-Perez HE, Quintanilla-Flores DL, Rodriguez-Gutierrez R, Gonzalez-Gonzalez JG, Tamez-Pena AL. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes. 2015 Jul 25;6(8):1073-81. doi: 10.4239/wjd.v6.i8.1073.

  PMID: 26240704 BACKGROUND

• Young P, Homlar KC. Extreme Postinjection Flare in Response to Intra-Articular Triamcinolone Acetonide (Kenalog). Am J Orthop (Belle Mead NJ). 2016 Mar-Apr;45(3):E108-11.

  PMID: 26991574 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Neil A Segal, MD, MS

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeannine Nilges, MD

CONTACT

913-574-0961; jnilges@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, assessors and biostatistician are blinded to the treatment allocation through use of physical blinds to the intervention being administered and coded participant ID's.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Blinded, Randomized Controlled Trial of 2 interventions

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 27, 2024
• Study Start: August 16, 2024
• Primary Completion (Estimated): July 16, 2026
• Study Completion (Estimated): October 16, 2026
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)