RCT to Evaluate the Effects of Zilretta (Triamcinolone Acetonide- Extended Release) and Kenalog (Triamcinolone Acetonide- Immediate Release) on Blood Glucose in Subjects With Osteoarthritis of the Knee and Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Percent of time spent with blood glucose >180 mg/dL
研究概览
简要总结
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.
详细描述
Protocol Title: A Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of ZILRETTA (Triamcinolone Acetonide-Extended Release) and TA-IR (Triamcinolone Acetonide-Immediate Release) on Blood Glucose Levels in Subjects with Osteoarthritis of the Knee and Type 2 Diabetes Mellitus Brief Title: Zilretta Diabetic Knee OA Regulatory Agency Identifier Number(s): IND 111325 Test Product, Dose, Mode of Administration, and Lot Number 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 Reference Product, Dose, Mode of Administration, and Lot Number 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 Current Indication: extended-release synthetic corticosteroid indicated as an IA injection for the management of osteoarthritis pain of the knee.
Study Population and Number of Study Subjects: Subjects with 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) Approximately 120 subjects (1:1 randomization, 60 ZILRETTA and 60 TA-IR) will be enrolled for this study.
Note: Subject is considered enrolled, if subject meets initial eligibility criteria and is randomized to a treatment arm.
Study Duration for Subjects:
Total study duration for individual subject will be about 4 months, which includes a 3-week Screening period, 10 days pretreatmentperiod, treatment day, and a 12-week post-treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Written consent to participate in the study.
- •Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.
- •3. Male or female ≥40 years of age.
- •Females with negative pregnancy test, who are not breastfeeding and have no intention to become pregnant during the time from screening through EOS.
- •5. Type 2 DM for at least 1 year prior to Screening.
- •Currently being treated with injectable (except insulin) and/or oral antidiabetic agents with stable doses for at least 1 month prior to Screening.
- •7. HbA1c 6.5-9% (in past 8 weeks).
- •Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m
- •(in past 8 weeks)
- •Triglycerides <500 mg/dL (in past 8 weeks)
- •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).
- •11. Currently meets modified ACR criteria (clinical and radiological) for OA (Altman et al, 1986) as follows:
- •At least 1 of the following:
- •Stiffness <30 minutes
- •Osteophytes
- •Index knee pain more than 15 days over the last month (as reported by the subject).
- •13. Kellgren-Lawrence Grade 2-
- •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.
- •15. Adequate BG data collected during the pretreatment phase (Day -10 through Day -1) ≥70% data available.
排除标准
- •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.
- •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).
- •Prior arthroscopic or open surgery of the index knee within 12 months of Screening.
- •Planned/anticipated surgery of the index knee or any other surgery during the study period.
- •Use of acetaminophen, or acetaminophen-containing products, from Screening through Day 14 (completion of post-treatment BG monitoring).
- •Subjects on Coumadins with INR ≥5 will be excluded (Bashir et al, 2015) Subject-related Criteria
- •Known hypersensitivity to any form of triamcinolone.
- •History of sarcoidosis or amyloidosis.
- •Active or history of malignancy within the last 3 years, except for resected basal cell carcinoma, squamous cell carcinoma of the skin, or effectively managed cervical carcinoma.
- •Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral, or parasitic infections or ocular herpes simplex.
- •Any infection requiring IV antibiotics within 4 weeks of Screening or infection requiring oral antibiotics within 2 weeks of Screening.
- •History of osteomyelitis.
- •Known or clinically suspected infection with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
- •Requiring or likely to require treatment with corticosteroids during the study period based on subject medical history.
- •History or active Cushing's or Addison's syndrome.
- •Active substance abuse (drugs or alcohol), history of chronic substance abuse within the last year, or prior chronic substance abuse judged by the Investigator likely to recur during the study.
- •Skin breakdown at the knee where the injection would take place.
- •Use of immunomodulators, immunosuppressives, or chemotherapeutic agents within 2 years of Screening.
- •Receipt of a live or live attenuated vaccine within 3 months of Screening.
- •Any other clinically significant psychiatric acute or chronic medical conditions that, in the judgment of the Investigator, would preclude the use of an IA corticosteroid or NSAIDs or that could compromise subject safety, limit the subject's ability to complete or adhere to the study, and/or compromise the objectives of the study.
研究组 & 干预措施
TA-ER
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
干预措施: triamcinolone acetonide extended-release injectable suspension; TCA-ER (Drug)
TA-IR
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
干预措施: Triamcinolone Acetonide- Immediate Release;TCA-IR (Drug)
结局指标
主要结局
Percent of time spent with blood glucose >180 mg/dL
时间窗: The primary outcome will be measured up to 72 hours after treatment by a sensor automatically uploading the data
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.
次要结局
- Change in 40m walk time(Between baseline and 12 weeks.)
- Percentage of time spent with blood glucose above >180 mg/dL(From baseline throughout 10 days follow-up.)
- Area under the curve (AUC) for cortisol levels(From baseline until the end-of-study (Day 85).)
- Number of blood glucose peaks ≥250 mg/dL(From baseline throughout 10 days follow-up)
- Change in stair climb time(Between baseline and 12 weeks.)
- Change in patient-reported physical function (KOOS-PS)(Between baseline and 12 weeks.)
- Change in quality of life (KOOS-QoL)(Between baseline and 12 weeks)