A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Acute Gouty Arthritis
- Conditions
- Acute Gouty Arthritis
- Interventions
- Drug: Anakinra 100 mgDrug: Triamcinolone Acetonide 40 mgDrug: Placebo to Anakinra 100 mgDrug: Placebo to Triamcinolone Acetonide 40 mg
- Registration Number
- NCT03002974
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
The purpose of this study is to evaluate how anakinra relieves pain for patients with acute gout that cannot take non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. The patients will be divided in different treatment groups to compare anakinra to the available drug triamcinolone.
- Detailed Description
Patients will be randomized to treatment at their first gout flare in the study. The first treatment period will be followed by an extension period during which the patients will receive the same treatment for any subsequent flares within 52 weeks of randomization of last patient in the study. The extension period for the individual patient in the study will be maximum two years (104 weeks). Each new flare treated will initiate a new series of study visits and assessments according to specified schedule of events. Only if a patient experience a new flare after Day 15 of the latest flare they can start a new treatment period. The comparison of primary interest is between anakinra (100 mg and 200 mg combined) and 40 mg triamcinolone, and as a secondary objective the 2 different doses of anakinra will be evaluated as well as assessment for subsequent flares.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 165
- Signed Informed consent
- Patient meeting the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2015 gout classification criteria
- History of ≥1 self-reported flares of gouty arthritis within 12 months
- Current ongoing flare of gouty arthritis characterized by pain intensity
- Currently tender and swollen joint
- Onset of current flare within 4 days
- Intolerant, unresponsive, contraindicated or not appropriate for treatment with NSAIDs and colchicine (both treatment options)
- If on urate-lowering therapy, on a stable dose and regimen
- Women of childbearing potential willing to use adequate contraception
Inclusion criteria for treatment of subsequent flare(s)
- Current flare of gouty arthritis characterized by pain intensity
- Currently tender and swollen joint
- Women of childbearing potential willing to use adequate contraception
- Use of specified pain relief medications or biologics (including glucocorticoids, narcotics, paracetamol/acetaminophen, NSAIDs, colchicine, IL-blockers and tumor necrosis factor inhibitors) within specified periods prior to randomization
- Contraindication to triamcinolone
- Polyarticular gouty arthritis involving more than 4 joints
- Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
- History of malignancy within the past 5 years. Exceptions are basal cell skin cancer, carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy.
- Known hypersensitivity to Escherichia coli-derived proteins, Kineret® (anakinra), Kenalog® (triamcinolone acetonide) or any components of the products.
- Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection
- Presence of severe renal function impairment chronic kidney disease (CKD) stages 4 and 5
- Presence of neutropenia
- Uncontrolled clinically significant hematologic, pulmonary, endocrine, metabolic, gastrointestinal, central nervous system or hepatic disease
- History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, New York Heart Association (NYHA) class III or IV heart failure within the previous 3 months
- Patients who have undergone major surgery within 2 weeks, or have an unhealed operation wound/s
- Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator might create risk to the patients or to the study.
- Earlier or current treatment with anakinra
- Pregnant or lactating women
- History of >12 flares overall in the 6 months prior to randomization
Exclusion criteria for treatment of subsequent flare(s):
- Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection.
- Presence of severe renal function impairment CKD stages 4 and 5
- Presence of neutropenia
- History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, NYHA class III or IV heart failure within the previous 3 months
- Patients who have undergone major surgery within 2 weeks or have an unhealed operation wound/s.
- Pregnant or lactating women.
- Presence of any condition or laboratory result that in the opinion of the investigator makes the patient not appropriate for treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anakinra 100 mg Anakinra 100 mg 1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg Anakinra 200 mg Anakinra 100 mg 2 subcutaneous injections of Anakinra 100 mg (2 syringes) once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg Anakinra 100 mg Placebo to Triamcinolone Acetonide 40 mg 1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg Triamcinolone 40 mg Placebo to Anakinra 100 mg 2 subcutaneous injections of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Triamcinolone Acetonide 40 mg Anakinra 200 mg Placebo to Triamcinolone Acetonide 40 mg 2 subcutaneous injections of Anakinra 100 mg (2 syringes) once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg Anakinra 100 mg Placebo to Anakinra 100 mg 1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg Triamcinolone 40 mg Triamcinolone Acetonide 40 mg 2 subcutaneous injections of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Triamcinolone Acetonide 40 mg
- Primary Outcome Measures
Name Time Method Change in Patient-assessed Pain Intensity in the Index Joint From Baseline to 24-72 Hours for the First Gout Flare Treated in the Study as Measured by VAS At baseline (pre-dose) and at 24, 48 and 72 hours for the first gout flare treated in the study Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100). Average of the assessments performed at 24, 48 and 72 hours.
- Secondary Outcome Measures
Name Time Method Median Time to Onset of Effect From baseline (predose) up to Day15 of the first flare treated in the study Onset of effect defined as 20% change from baseline pain intensity in the index joint on a visual analogue scale (VAS)
Median Time to First Intake of Rescue Medication From First Investigational Drug Administration From Day 1 to Day 15 for the first flare treated Time to first intake of rescue medication for acute gout, measured in hours from first investigational drug administration
Change From Baseline in the Inflammatory Biomarker C Reactive Protein baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study This endpoint represents the change from baseline, mg/dL, of the inflammatory biomarker C reactive protein
Serum Concentration of Endogenous Interleukin-1 Receptor Antagonist /Anakinra Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated during the extension period This endpoint represents the level of of endogenous interleukin-1 receptor antagonist /anakinra
Change From Baseline in Health Related Quality of Life EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) at baseline, Day 8 and Day 15 for the first flare treated in the study Exploratory objective. The EQ-5D-5L, a self-report questionnaire, is a descriptive system of Health related quality of life (HRQL) states consisting of 5 dimensions (Mobility, Self-care, Usual activities, Pain/Discomfort, Anxiety/Depression), each of which can have 5 responses. The responses record 5 levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Change From Baseline in the Inflammatory Biomarker Serum Amyloid A baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study This endpoint represents the change from baseline, mg/L, of the inflammatory biomarker Serum amyloid A
Median Time to Response From baseline (predose) up to Day15 of the first flare treated in the study Response defined as 50% change from baseline pain intensity on a visual analogue scale (VAS)
Physician's Assessment of Clinical Signs in Index Joint: Tenderness at 72 hours, Day 8 and Day 15 for the first flare treated in the study 4-point Likert scale (0=no pain, 1= mild/patient states there is pain when touched, 2= moderate/patient states there is pain and Winces, 3=severe/patient states there is pain, winces and withdraws
Physician's Assessment of Clinical Signs in Index Joint: Erythema at 72 hours, Day 8 and Day 15 for the first flare treated in the study Physicians assessment of clinical signs with 2 outcomes: Absent=no erythema, present=erythema
Proportion of Patients With Anti-drug Antibodies (ADA) Against Anakinra Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated treated during the extension period Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies
Change in Patient-assessed Pain Intensity in the Index Joint From Baseline at Time Points From 6 Hours to 8 Days for the First Gout Flare Treated in the Study as Measured by 5-point Likert Scale At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 5-point Likert scale (0-4 point scale: "none", "mild", "moderate", "severe", "extreme") at time points baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8.
Median Time to Resolution of Pain From baseline (predose) up to Day15 of the first flare Resolution of pain defined as \<10 mm on VAS, a continuous 0 to 100 mm visual analogue scale, ranging from no pain (0) to unbearable pain (100), in the index joint
Physician's Assessment of Global Response to Treatment At 72 hours, Day 8 and Day 15 for the first flare treated in the study 5-point Likert scale (0- to 4-point scale: "none", "mild", "moderate", "severe, "extreme") where higher score mean worse outcome
Physician's Assessment of Clinical Signs in Index Joint: Swelling at 72 hours, Day 8 and Day 15 for the first flare treated in the study 4-point Likert scale (0=no swelling, 1= mild swelling, 2=moderate swelling, 3=severe swelling or bulging beyond joint margins)
Proportion of Patients With Neutralizing Antibodies Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated during the extension period Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies
Health Care Resource Utilization Due to a Gouty Arthritis Flare Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period Exploratory objective: number of days with hospitalization and un-scheduled outpatient visits
Patient´s Assessment of Global Response to Treatment (5-point Likert Scale) at 72 hours, Day 8 and Day 15 for the first flare treated in the study 5-point Likert scale (0- to 4-point scale: 0=excellent, 1=very good, 2=good, 3=fair, 4=poor response to treatment) where lower rate indicates better response to treatment
The Percent of Patients With at Least One Adverse Event Through study completion, at 12 weeks after last flare treated during the extension period All adverse events to be recorded Day 1 - Day 28 for each flare. Serious adverse events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
The Percent of Patients With at Least One Serious Adverse Event, Including Death Through study completion, at 12 weeks after last flare treated during the extension period Serious Adverse Events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
Change From Baseline in Short Form (36) Health Survey, Acute Version 2 (SF-36®) Physical Functioning Domain Score at baseline, Day 8 and Day 15 for the first flare treated in the study SF-36® measures the impact of disease on overall quality of life. It consists of 8 individual domains. Score range from 0 to 100, where 0 represents the worst possible health and 100 is perfect health.
Percent Impairment While Working During Last Week Due to Gout During the First Flare and Subsequent Flares Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period The WPAI yeilds four types of scores of which Work productivity loss is one.
SHP is derived from WPAI as follows:
The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity as follows:
Questions:
Q1 = currently employed Q2 = hours missed due to specified problem Q3 = hours missed other reasons Q4 = hours actually worked Q5 = degree problem affected productivity while working Q6 = degree problem affected regular activities
Scores:
Multiply scores by 100 to express in percentages. Percent impairment while working due to problem: Q5/10 The answer on Q5 is given on a scale from 0 (PROBLEM had no effect on work) to 10 (PROBLEM completely prevented me from working).
Thus the analysis values from which mean and SD have been calculated and reported are the outcomes from Q5 (ranging from 0 to 10) multiplied with 100 and divided by 10.
Trial Locations
- Locations (37)
Clinical Trials Management
🇺🇸Metairie, Louisiana, United States
Clinical Research Solutions - Franklin
🇺🇸Franklin, Tennessee, United States
Advanced Research Center
🇺🇸Anaheim, California, United States
Corporation Lane Internal Medicine and Research Center
🇺🇸Virginia Beach, Virginia, United States
The Research Group of Lexington
🇺🇸Lexington, Kentucky, United States
Meridien Research
🇺🇸Brooksville, Florida, United States
Health Awareness
🇺🇸Jupiter, Florida, United States
Kaushik Amin MD
🇺🇸Conyers, Georgia, United States
Clinical Investigations Specialists, Inc.
🇺🇸Kenosha, Wisconsin, United States
Advanced Clinical Research - West Jordan
🇺🇸West Jordan, Utah, United States
Lemah Creek Clinical Research
🇺🇸Melrose Park, Illinois, United States
Ericksen Research & Development
🇺🇸Clinton, Utah, United States
Well Pharma Medical Research
🇺🇸Miami, Florida, United States
Fundamental Research, LLC
🇺🇸Gulf Shores, Alabama, United States
Coastal Clinical Research, Inc
🇺🇸Mobile, Alabama, United States
Delta Waves Sleep Disorder and Research Center
🇺🇸Colorado Springs, Colorado, United States
Pulmonary Associates of Brandon
🇺🇸Brandon, Florida, United States
Alta Pharmaceutical Research Center
🇺🇸Dunwoody, Georgia, United States
Boiling Springs Medical Research, Inc.
🇺🇸Shelby, North Carolina, United States
Clinical Research Solutions
🇺🇸Smyrna, Tennessee, United States
Renaissance Clinical Research and Hypertension Clinic of Texas, PLLC
🇺🇸Dallas, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
Accurate Clinical Management
🇺🇸Pasadena, Texas, United States
Wade Family Medicine
🇺🇸Bountiful, Utah, United States
Mileground Physicians, PLLC
🇺🇸Morgantown, West Virginia, United States
Albuquerque Clinical Trials
🇺🇸Albuquerque, New Mexico, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Clinical Neuroscience Solutions
🇺🇸Orlando, Florida, United States
Clinical Research Trials of Florida
🇺🇸Tampa, Florida, United States
Sun Research Institute
🇺🇸San Antonio, Texas, United States
Meridien Research, Inc
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
PMG Research of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Hightop Medical Research Center
🇺🇸Cincinnati, Ohio, United States
New Horizons Clinical Research
🇺🇸Cincinnati, Ohio, United States
Commonwealth Clinical Research Specialists, Inc.
🇺🇸Richmond, Virginia, United States