Clinical trial NCT03636373: Pilot Study Evaluating The Efficacy Of Etanercept In Acute Gout
Official title: Investigator-Initiated, Pilot Study Evaluating The Efficacy Of Etanercept In Acute Gout
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Gout Attack
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2018-08-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Joint Pain Intensity in the Most Affected Joint
timeFrame: 72 hours
Secondary outcomes:
measure: Joint Pain on Numeric Pain Scale
timeFrame: Baseline, Days 4, 7, and 14
measure: Patient's Assessment of Response to Treatment
timeFrame: Day 4, 7 and 14
measure: Physician's Assessment of Response to Treatment
timeFrame: Post-dose days 4, 7 and 14
measure: Rescue Medication
timeFrame: Day 1 (Baseline visit - Visit 1) through Day 14 (Visit 4).
measure: Safety and Tolerability of Etanercept
timeFrame: Day 1 (Baseline visit - Visit 1) through Day 30 (Safety follow up phone visit -Visit 5)
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers, Robert Wood Johnson Medical School, Clinical Research Center
state: New Jersey
Study officials:
affiliation: Rutgers Robert Wood Johnson Medical School/ Rutgers RWJMS Gout center
name: Naomi Schlesinger, MD
role: PRINCIPAL_INVESTIGATOR
References: