A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Acute Gouty Arthritis (anaGO)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Gouty Arthritis
• Intervention / Treatment: Drug: Anakinra 100 mg; Drug: Placebo to Anakinra 100 mg; Drug: Placebo to Triamcinolone Acetonide 40 mg; Drug: Triamcinolone Acetonide 40 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Gulf Shores, Alabama, United States, 36542
      • Fundamental Research, LLC
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves Sleep Disorder and Research Center
  • Florida
    • Brandon, Florida, United States, 33511
      • Pulmonary Associates of Brandon
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions
    • Tampa, Florida, United States, 33607
      • Clinical Research Trials of Florida
    • Tampa, Florida, United States, 33634
      • Meridien Research, Inc
  • Georgia
    • Conyers, Georgia, United States, 30013
      • Kaushik Amin MD
    • Dunwoody, Georgia, United States, 30338
      • Alta Pharmaceutical Research Center
  • Illinois
    • Melrose Park, Illinois, United States, 60160
      • Lemah Creek Clinical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5422
      • University of Michigan
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Shelby, North Carolina, United States, 28150
      • Boiling Springs Medical Research, Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States, 45224
      • Hightop Medical Research Center
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Clinical Research Solutions - Franklin
    • Smyrna, Tennessee, United States, 37167
      • Clinical Research Solutions
  • Texas
    • Dallas, Texas, United States, 75234
      • Renaissance Clinical Research and Hypertension Clinic of Texas, PLLC
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions, Inc.
    • Pasadena, Texas, United States, 77505
      • Accurate Clinical Management
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Utah
    • Bountiful, Utah, United States, 84010
      • Wade Family Medicine
    • Clinton, Utah, United States, 84015
      • Ericksen Research & Development
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research - West Jordan
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Commonwealth Clinical Research Specialists, Inc.
    • Virginia Beach, Virginia, United States, 23462
      • Corporation Lane Internal Medicine and Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Mileground Physicians, PLLC
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
      • Clinical Investigations Specialists, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Anakinra 100 mg; 100 mg/0.67 mL solution in single-use prefilled syringes for subcutaneous injection; Other Names: Kineret; Drug: Placebo to Anakinra 100 mg; sterile solution for injection (0.67 mL) in a single-use prefilled syringe identical to the anakinra syringe; Other Names: Placebo Kineret; Drug: Placebo to Triamcinolone Acetonide 40 mg; 1 mL intramuscular injectable suspension with identical appearance as the Triamcinolone Acetonide suspension; Other Names: Placebo Kenalog
Experimental: Anakinra 200 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	Drug: Anakinra 100 mg; 100 mg/0.67 mL solution in single-use prefilled syringes for subcutaneous injection; Other Names: Kineret; Drug: Placebo to Triamcinolone Acetonide 40 mg; 1 mL intramuscular injectable suspension with identical appearance as the Triamcinolone Acetonide suspension; Other Names: Placebo Kenalog
Active Comparator: Triamcinolone 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	Drug: Placebo to Anakinra 100 mg; sterile solution for injection (0.67 mL) in a single-use prefilled syringe identical to the anakinra syringe; Other Names: Placebo Kineret; Drug: Triamcinolone Acetonide 40 mg; 1 mL intramuscular injection of a 40 mg/mL injectable suspension; Other Names: Triamcinolone; Kenalog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	At baseline (pre-dose) and at 24, 48 and 72 hours for the first gout flare treated in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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
Median Time to Onset of Effect	Onset of effect defined as 20% change from baseline pain intensity in the index joint on a visual analogue scale (VAS)	From baseline (predose) up to Day15 of the first flare treated in the study
Median Time to Response	Response defined as 50% change from baseline pain intensity on a visual analogue scale (VAS)	From baseline (predose) up to Day15 of the first flare treated in the study
Median Time to Resolution of Pain	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	From baseline (predose) up to Day15 of the first flare
Median Time to First Intake of Rescue Medication From First Investigational Drug Administration	Time to first intake of rescue medication for acute gout, measured in hours from first investigational drug administration	From Day 1 to Day 15 for the first flare treated
Physician's Assessment of Global Response to Treatment	5-point Likert scale (0- to 4-point scale: "none", "mild", "moderate", "severe, "extreme") where higher score mean worse outcome	At 72 hours, Day 8 and Day 15 for the first flare treated in the study
Physician's Assessment of Clinical Signs in Index Joint: Tenderness	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	at 72 hours, Day 8 and Day 15 for the first flare treated in the study
Physician's Assessment of Clinical Signs in Index Joint: Swelling	4-point Likert scale (0=no swelling, 1= mild swelling, 2=moderate swelling, 3=severe swelling or bulging beyond joint margins)	at 72 hours, Day 8 and Day 15 for the first flare treated in the study
Physician's Assessment of Clinical Signs in Index Joint: Erythema	Physicians assessment of clinical signs with 2 outcomes: Absent=no erythema, present=erythema	at 72 hours, Day 8 and Day 15 for the first flare treated in the study
Patient´s Assessment of Global Response to Treatment (5-point Likert Scale)	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	at 72 hours, Day 8 and Day 15 for the first flare treated in the study
Change From Baseline in the Inflammatory Biomarker C Reactive Protein	This endpoint represents the change from baseline, mg/dL, of 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
Change From Baseline in the Inflammatory Biomarker Serum Amyloid A	This endpoint represents the change from baseline, mg/L, of 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
The Percent of Patients With at Least One Adverse Event	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.	Through study completion, at 12 weeks after last flare treated during the extension period
The Percent of Patients With at Least One Serious Adverse Event, Including Death	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.	Through study completion, at 12 weeks after last flare treated during the extension period
Serum Concentration of Endogenous Interleukin-1 Receptor Antagonist /Anakinra	This endpoint represents the level of 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
Proportion of Patients With Anti-drug Antibodies (ADA) Against Anakinra	Confirmed ADA positive samples will be analysed for the presence of 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 treated during the extension period
Proportion of Patients With Neutralizing Antibodies	Confirmed ADA positive samples will be analysed for the presence of 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
Change From Baseline in Short Form (36) Health Survey, Acute Version 2 (SF-36®) Physical Functioning Domain Score	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.	at baseline, Day 8 and Day 15 for the first flare treated in the study
Change From Baseline in Health Related Quality of Life EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)	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.	at baseline, Day 8 and Day 15 for the first flare treated in the study
Percent Impairment While Working During Last Week Due to Gout During the First Flare and Subsequent Flares	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.	Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period
Health Care Resource Utilization Due to a Gouty Arthritis Flare	Exploratory objective: number of days with hospitalization and un-scheduled outpatient visits	Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Investigators: Study Director: Sven Ohlman, MD, PhD, Swedish Orphan Biovitrum AB

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 26, 2016

Study Record Updates

• Last Update Posted (Actual): July 15, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Gout; IL-1 receptor antagonist; Interleukin 1 receptor antagonist
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Arthritis; Arthritis, Gouty; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: Sobi.ANAKIN-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No