Clinical trial NCT03002974: A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Acute Gouty Arthritis
Official title: A Randomized, Double-blind, Active-control, Multicenter, Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra Compared to Intramuscular Triamcinolone in the Treatment of Acute Gouty Arthritis, Followed by an Extension Period of up to 2 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Gouty Arthritis
Keywords: Gout
Interleukin 1 receptor antagonist
IL-1 receptor antagonist
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2016-12-26
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: At baseline (pre-dose) and at 24, 48 and 72 hours for the first gout flare treated in the study
Secondary outcomes:
measure: 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
timeFrame: 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
measure: Median Time to Onset of Effect
timeFrame: From baseline (predose) up to Day15 of the first flare treated in the study
measure: Median Time to Response
timeFrame: From baseline (predose) up to Day15 of the first flare treated in the study
measure: Median Time to Resolution of Pain
timeFrame: From baseline (predose) up to Day15 of the first flare
measure: Median Time to First Intake of Rescue Medication From First Investigational Drug Administration
timeFrame: From Day 1 to Day 15 for the first flare treated
measure: Physician's Assessment of Global Response to Treatment
timeFrame: At 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Physician's Assessment of Clinical Signs in Index Joint: Tenderness
timeFrame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Physician's Assessment of Clinical Signs in Index Joint: Swelling
timeFrame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Physician's Assessment of Clinical Signs in Index Joint: Erythema
timeFrame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Patient´s Assessment of Global Response to Treatment (5-point Likert Scale)
timeFrame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Change From Baseline in the Inflammatory Biomarker C Reactive Protein
timeFrame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: Change From Baseline in the Inflammatory Biomarker Serum Amyloid A
timeFrame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study
measure: The Percent of Patients With at Least One Adverse Event
timeFrame: Through study completion, at 12 weeks after last flare treated during the extension period
measure: The Percent of Patients With at Least One Serious Adverse Event, Including Death
timeFrame: Through study completion, at 12 weeks after last flare treated during the extension period
measure: Serum Concentration of Endogenous Interleukin-1 Receptor Antagonist /Anakinra
timeFrame: 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
measure: Proportion of Patients With Anti-drug Antibodies (ADA) Against Anakinra
timeFrame: 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
measure: Proportion of Patients With Neutralizing Antibodies
timeFrame: 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
measure: Change From Baseline in Short Form (36) Health Survey, Acute Version 2 (SF-36®) Physical Functioning Domain Score
timeFrame: at baseline, Day 8 and Day 15 for the first flare treated in the study
measure: Change From Baseline in Health Related Quality of Life EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)
timeFrame: at baseline, Day 8 and Day 15 for the first flare treated in the study
measure: Percent Impairment While Working During Last Week Due to Gout During the First Flare and Subsequent Flares
timeFrame: Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period
measure: Health Care Resource Utilization Due to a Gouty Arthritis Flare
timeFrame: Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gulf Shores
country: United States
facility: Fundamental Research, LLC
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc
state: Alabama
city: Anaheim
country: United States
facility: Advanced Research Center
state: California
city: Colorado Springs
country: United States
facility: Delta Waves Sleep Disorder and Research Center
state: Colorado
city: Brandon
country: United States
facility: Pulmonary Associates of Brandon
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida
state: Florida
city: Tampa
country: United States
facility: Meridien Research, Inc
state: Florida
city: Conyers
country: United States
facility: Kaushik Amin MD
state: Georgia
city: Dunwoody
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Melrose Park
country: United States
facility: Lemah Creek Clinical Research
state: Illinois
city: Lexington
country: United States
facility: The Research Group of Lexington
state: Kentucky
city: Metairie
country: United States
facility: Clinical Trials Management
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Shelby
country: United States
facility: Boiling Springs Medical Research, Inc.
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Cincinnati
country: United States
facility: Hightop Medical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Franklin
country: United States
facility: Clinical Research Solutions - Franklin
state: Tennessee
city: Smyrna
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Dallas
country: United States
facility: Renaissance Clinical Research and Hypertension Clinic of Texas, PLLC
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Pasadena
country: United States
facility: Accurate Clinical Management
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Bountiful
country: United States
facility: Wade Family Medicine
state: Utah
city: Clinton
country: United States
facility: Ericksen Research & Development
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research - West Jordan
state: Utah
city: Richmond
country: United States
facility: Commonwealth Clinical Research Specialists, Inc.
state: Virginia
city: Virginia Beach
country: United States
facility: Corporation Lane Internal Medicine and Research Center
state: Virginia
city: Morgantown
country: United States
facility: Mileground Physicians, PLLC
state: West Virginia
city: Kenosha
country: United States
facility: Clinical Investigations Specialists, Inc.
state: Wisconsin
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Sven Ohlman, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Saag KG, Khanna PP, Keenan RT, Ohlman S, Osterling Koskinen L, Sparve E, Akerblad AC, Wiken M, So A, Pillinger MH, Terkeltaub R. A Randomized, Phase II Study Evaluating the Efficacy and Safety of Anakinra in the Treatment of Gout Flares. Arthritis Rheumatol. 2021 Aug;73(8):1533-1542. doi: 10.1002/art.41699. Epub 2021 Jul 7.