Pilot Study Evaluating The Efficacy Of Etanercept In Acute Gout

Study Overview
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Brief Summary
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The purpose of this pilot study is to investigate the safety and efficacy of etanercept (Enbrel™; Amgen) for the treatment of an acute gout attack will be non-inferior to triamcinolone acetonide an FDA approved drug to treat acute gout attacks.

Detailed Description
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The study was designed as a 14-day, two center- pilot randomized, active-controlled, double-blind, study. The study was approved by the Institutional Review Board (IRB) Pro2018000562. Patients were screened for eligibility at the time of an acute flare. Patients aged 28-55 years with an acute gout flare meeting the validated definition of flare were enrolled (12). Onset of current acute gout flare was within 3 days prior to randomization and baseline pain intensity ≥50 mm on a 0-100 mm visual analogue scale (VAS), Gout patients were defined by a confirmed diagnosis of crystal proven gout and or a score of ≥ 8 on the 2015 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Gout Classification Criteria (13). Patients recorded pain intensity in the most affected joint prior to treatment. Efficacy, including pain on a 0-100 mm VAS, and safety assessments were conducted at 24 and 72 hours, 7 and 14 days after baseline.

Official Title
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Investigator-Initiated, Pilot Study Evaluating The Efficacy Of Etanercept In Acute Gout

Conditions
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Gout Attack

Intervention / Treatment
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* Drug: Etanercept
* Drug: Triamcinolone Acetonide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female patients age ≥18 to ≤85 year History of established gout Onset of current acute gout attack within 4 days prior to randomization with: presence of any warm joint, swollen joint, pain score at rest ≥5 on the 0-10 pain scale, patient self-report of acute gout attack Baseline pain intensity ≥5 on a 0-10 pain scale; Tender (≥1 on a 0-4-point Likert scale) and swollen (≥1 on a 0-4-point Likert scale) index joint; If on urate-lowering therapy, a stable dose and regimen for at least 2 weeks prior to randomization, and expectance to remain on a stable dose and regimen for the duration of the double-blind treatment period, and; Body mass index (BMI) ≤45 kg/m2. Exclusion Criteria: Use of intra-articular or IM corticosteroids within 14 days prior to screening; Use of an IL-1 inhibitor, TNF inhibitor or other biologic or investigational drug within 30 days prior to screening; History of a drug allergy to either study drug; Diagnosis or history of: rheumatoid arthritis (RA); infectious/septic or other inflammatory arthritis; alcoholic hepatitis or nonalcoholic steatohepatitis; immunodeficiency syndromes, including Human Immunodeficiency Virus (HIV) infection; Stage IIIb, IV, or V chronic kidney disease; idiopathic thrombocytopenic purpura; active, severe chronic pulmonary disease (eg, requiring oxygen therapy); uncontrolled hypertension (≥ 200/105 mmHg); symptomatic (New York Heart Association Class II, III, or IV) congestive heart failure; uncontrolled diabetes Type I or II (recent blood glucose > 300 mg/dL); myocardial infarction, unstable cardiac arrhythmias or unstable symptomatic coronary ischemia, within the past 12 months before randomization; history of malignancy of any organ system within the past 5 years; multiple sclerosis or any other demyelinating disease, or; major chronic inflammatory disease or connective tissue disease other than RA or psoriatic arthritis (PsA), including but not limited to fibromyalgia or systemic lupus erythematosus (with the exception of secondary Sjögrens syndrome, etc.); Contraindication to IM injection; Donation or loss of ≥400 milliliters (mL) of blood in the 8 weeks before dosing; Any live vaccination in the 3 months before the start of the study; Active infection (including chronic or localized infections) for which antiinfectives were indicated within 4 weeks before screening; Any serious infection, defined as requiring hospitalization or intravenous anti-infectives, within 8 weeks before first dose of investigational product; Prosthetic joint infection within 5 years of screening, or native joint infection within 1 year of screening; Known alcohol addiction or dependency, daily alcohol use, or current substance use or abuse; Positive medical history for hepatitis B or C (subjects with a history of hepatitis B vaccination without history of hepatitis B infection are allowed to enroll); History of active tuberculosis; Positive test for tuberculosis during screening, defined as positive Purified Protein Derivative (PPD) skin test (≥5 mm induration at 48-72 hours after test is placed), or positive Quantiferon test; Pregnant or nursing (lactating) women Female patients who are physiologically capable of becoming pregnant must use an acceptable method of contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be administered a single dose of etanercept 50 mg subcutaneously (SC), at the onset of an acute gout attack, or a single dose of triamcinolone acetonide 40 mg intramuscularly (IM)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept<br>Subjects will be administered etanercept 50 mg subcutaneously and a placebo intramuscularly | Drug: Etanercept<br>* Subjects will receive 50 mg of study drug on visit 1. A second dose of study drug will be administered if the pain intensity is ≥ 5 on a pain scale of 0-10 at Visit 2<br>|
| Active Comparator: Triamcinolone acetonide<br>Subjects will be administered triamcinolone acetonide 40 mg intramuscularly and a placebo subcutaneously | Drug: Triamcinolone Acetonide<br>* Subjects will be administered triamcinolone acetonide 40 mg intramuscularly on visit 1. A second dose of drug will be administered if the pain intensity is ≥ 5 on a pain scale of 0-10 at Visit 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint Pain Intensity in the Most Affected Joint | Pain intensity in the most affected baseline joint measured by the numeric 0-10 Visual Analog Scale at 72 hours with 0 indicating no pain and 10 indicating intense pain. Higher score indicating a worse outcome. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint Pain on Numeric Pain Scale | Patient's assessment of joint pain intensity in the most affected baseline joint on a numeric 0-10 Visual Analog Scale at Baseline and post-dose Days with 0 indicating no pain and 10 indicating intense pain. Higher score indicating a worse outcome. | Baseline, Days 4, 7, and 14 | 
| Patient's Assessment of Response to Treatment | Patient's global assessment of response to treatment (Likert), options are None, Poor, Acceptable, Good, Excellent | Day 4, 7 and 14 | 
| Physician's Assessment of Response to Treatment | Physician's global assessment of response to treatment None, Poor, Acceptable, Good, Excellent | Post-dose days 4, 7 and 14 | 
| Rescue Medication | Total number of patients taking rescue medication after the administration of study medication while on study. Compare the use of rescue medication in etanercept and triamcinolone acetonide patients: for those patients having difficulty tolerating their pain, despite the treatment, were allowed to take rescue medication for pain. A paper diary was given to each patient at baseline visit to record the rescue medications. | Day 1 (Baseline visit - Visit 1) through Day 14 (Visit 4). | 
| Safety and Tolerability of Etanercept | Safety and tolerability as assessed by subjects with adverse events and serious adverse events from baseline through Visit 5 safety follow-up | Day 1 (Baseline visit - Visit 1) through Day 30 (Safety follow up phone visit -Visit 5) |