Pilot Study Evaluating The Efficacy Of Etanercept In Acute Gout

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

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.

Study Overview

• Status: Terminated
• Conditions: Gout Attack
• Intervention / Treatment: Drug: Etanercept; Drug: Triamcinolone Acetonide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers, Robert Wood Johnson Medical School, Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male or female patients age ≥18 to ≤85 year
2. History of established gout
3. 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
4. Baseline pain intensity ≥5 on a 0-10 pain scale;
5. Tender (≥1 on a 0-4-point Likert scale) and swollen (≥1 on a 0-4-point Likert scale) index joint;
6. 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;
7. Body mass index (BMI) ≤45 kg/m2.

Exclusion Criteria:

1. Use of intra-articular or IM corticosteroids within 14 days prior to screening;
2. Use of an IL-1 inhibitor, TNF inhibitor or other biologic or investigational drug within 30 days prior to screening;
3. History of a drug allergy to either study drug;

4. Diagnosis or history of:

   1. rheumatoid arthritis (RA);
   2. infectious/septic or other inflammatory arthritis;
   3. alcoholic hepatitis or nonalcoholic steatohepatitis;
   4. immunodeficiency syndromes, including Human Immunodeficiency Virus (HIV) infection;
   5. Stage IIIb, IV, or V chronic kidney disease;
   6. idiopathic thrombocytopenic purpura;
   7. active, severe chronic pulmonary disease (eg, requiring oxygen therapy);
   8. uncontrolled hypertension (≥ 200/105 mmHg);
   9. symptomatic (New York Heart Association Class II, III, or IV) congestive heart failure;
   10. uncontrolled diabetes Type I or II (recent blood glucose > 300 mg/dL);
   11. myocardial infarction, unstable cardiac arrhythmias or unstable symptomatic coronary ischemia, within the past 12 months before randomization;
   12. history of malignancy of any organ system within the past 5 years;
   13. multiple sclerosis or any other demyelinating disease, or;
   14. 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.);
5. Contraindication to IM injection;
6. Donation or loss of ≥400 milliliters (mL) of blood in the 8 weeks before dosing;
7. Any live vaccination in the 3 months before the start of the study;
8. Active infection (including chronic or localized infections) for which antiinfectives were indicated within 4 weeks before screening;
9. Any serious infection, defined as requiring hospitalization or intravenous anti-infectives, within 8 weeks before first dose of investigational product;
10. Prosthetic joint infection within 5 years of screening, or native joint infection within 1 year of screening;
11. Known alcohol addiction or dependency, daily alcohol use, or current substance use or abuse;
12. 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);
13. History of active tuberculosis;
14. 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;
15. Pregnant or nursing (lactating) women
16. Female patients who are physiologically capable of becoming pregnant must use an acceptable method of contraception

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etanercept; Subjects will be administered etanercept 50 mg subcutaneously and a placebo intramuscularly	Drug: Etanercept; 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
Active Comparator: Triamcinolone acetonide; Subjects will be administered triamcinolone acetonide 40 mg intramuscularly and a placebo subcutaneously	Drug: Triamcinolone Acetonide; 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: Amgen
• Investigators: Principal Investigator: Naomi Schlesinger, MD, Rutgers Robert Wood Johnson Medical School/ Rutgers RWJMS Gout center

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2019
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): August 13, 2021

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 15, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Etanercept; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: Pro2018000562

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes