Gout Attack
Conditions
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.
Interventions
DRUGEtanercept
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
DRUGTriamcinolone 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
Sponsors
Amgen
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Triple
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Joint Pain Intensity in the Most Affected Joint | 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Joint Pain on Numeric Pain Scale | Baseline, Days 4, 7, and 14 | 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. |
| Patient's Assessment of Response to Treatment | Day 4, 7 and 14 | Patient's global assessment of response to treatment (Likert), options are None, Poor, Acceptable, Good, Excellent |
| Physician's Assessment of Response to Treatment | Post-dose days 4, 7 and 14 | Physician's global assessment of response to treatment None, Poor, Acceptable, Good, Excellent |
| Rescue Medication | Day 1 (Baseline visit - Visit 1) through Day 14 (Visit 4). | 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. |
| Safety and Tolerability of Etanercept | Day 1 (Baseline visit - Visit 1) through Day 30 (Safety follow up phone visit -Visit 5) | Safety and tolerability as assessed by subjects with adverse events and serious adverse events from baseline through Visit 5 safety follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etanercept Subjects will be administered etanercept 50 mg subcutaneously and a placebo intramuscularly
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 Visual Analog Scale (VAS) of 0-10 at Visit 2 with 0 indicating no pain and 10 indicating intense pain. | 3 |
| Triamcinolone Acetonide Subjects will be administered triamcinolone acetonide 40 mg intramuscularly and a placebo subcutaneously
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 Visual Analog Scale (VAS) of 0-10 at Visit 2 with 0 indicating no pain and 10 indicating intense pain. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study closure due to Covid-19 | 1 | 0 |
Baseline characteristics
| Characteristic | Etanercept | Total | Triamcinolone Acetonide |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Patient reported pain | 7.67 units on a scale | 7.00 units on a scale | 6.00 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 1 / 3 | 1 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
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.
Time frame: 72 hours
Population: Evaluate the efficacy of etanercept, compared to triamcinolone acetonide in patients with acute gout attack
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Etanercept | Joint Pain Intensity in the Most Affected Joint | 5 score on a scale |
| Triamcinolone Acetonide | Joint Pain Intensity in the Most Affected Joint | 1.5 score on a scale |
Comparison: Mean Outcome measure Etanercept arm { ( 8 + 0 + 7)/3 = 5} Triamcinolone Arm { (3+0) /2 = 1.5 }p-value: 1t-test, 1 sided
Secondary
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.
Time frame: Baseline, Days 4, 7, and 14
Population: 2 patients were enrolled in Triamcinolone acetonide arm and 3 patients were enrolled in Etanercept arm. However only two patients in the Etanercept arm completed the study. One patient completed only 2 study visits since the study was put on hold due to COVID-19 pandemic.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etanercept | Joint Pain on Numeric Pain Scale | Visit 1 (Baseline) | 6 score on a scale |
| Etanercept | Joint Pain on Numeric Pain Scale | Visit 2 (Day 4) | 1.5 score on a scale |
| Etanercept | Joint Pain on Numeric Pain Scale | Visit 3 (Day 7) | 1 score on a scale |
| Etanercept | Joint Pain on Numeric Pain Scale | Visit 4 (Day 14) | 1 score on a scale |
| Triamcinolone Acetonide | Joint Pain on Numeric Pain Scale | Visit 4 (Day 14) | 0.5 score on a scale |
| Triamcinolone Acetonide | Joint Pain on Numeric Pain Scale | Visit 1 (Baseline) | 7.67 score on a scale |
| Triamcinolone Acetonide | Joint Pain on Numeric Pain Scale | Visit 3 (Day 7) | 3 score on a scale |
| Triamcinolone Acetonide | Joint Pain on Numeric Pain Scale | Visit 2 (Day 4) | 5 score on a scale |
p-value: 1t-test, 2 sided
Secondary
Patient's Assessment of Response to Treatment
Patient's global assessment of response to treatment (Likert), options are None, Poor, Acceptable, Good, Excellent
Time frame: Day 4, 7 and 14
Population: 4 subjects completed the study with 2 in each arm. Additionally, 1 more subject completed 2 visits (Day 1 and Day 4) only 2 visits in Etanercept arm. Therefore, 2 subjects in Triamcinolone acetonide completed Visit 2 while 3 subjects in Etanercept arm completed this Visit. However, out of the 2 participants who completed all study visits in the Etanercept arm, only 1 participant completed Patient's assessment of response to treatment. Thus, only 1 participant was included in analysis.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Etanercept | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Excellent | 1 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Good | 2 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Poor | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Excellent | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | None | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | None | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Good | 1 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Poor | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Poor | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Acceptable | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Acceptable | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Good | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Acceptable | 0 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Excellent | 2 Participants |
| Etanercept | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | None | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Excellent | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | None | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Poor | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Acceptable | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Good | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 4 (Day 14) | Excellent | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | None | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Poor | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Acceptable | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Good | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 2 (Day 4) | Excellent | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | None | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Poor | 1 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Acceptable | 0 Participants |
| Triamcinolone Acetonide | Patient's Assessment of Response to Treatment | Visit 3 (Day 7) | Good | 0 Participants |
p-value: 0.05t-test, 2 sided
Secondary
Physician's Assessment of Response to Treatment
Physician's global assessment of response to treatment None, Poor, Acceptable, Good, Excellent
Time frame: Post-dose days 4, 7 and 14
Population: 2 patients were enrolled in Triamcinolone acetonide arm and 3 patients were enrolled in Etanercept arm. However only two patients in the Etanercept arm completed the study. One patient completed only 2 study visits since the study was put on hold due to COVID-19 pandemic.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Etanercept | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Acceptable | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | None | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Poor | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Good | 1 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Excellent | 1 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | None | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Poor | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Acceptable | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Good | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Excellent | 2 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | None | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Poor | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Acceptable | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Good | 0 Participants |
| Etanercept | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Excellent | 2 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Acceptable | 1 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Acceptable | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Good | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | None | 1 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Acceptable | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Poor | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Excellent | 1 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Good | 2 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Excellent | 1 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 2 (Day 4) | Excellent | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | None | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | None | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Good | 1 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 3 (Day 7) | Poor | 0 Participants |
| Triamcinolone Acetonide | Physician's Assessment of Response to Treatment | Visit 4 (Day 14) | Poor | 0 Participants |
p-value: 0.05t-test, 2 sided
Secondary
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.
Time frame: Day 1 (Baseline visit - Visit 1) through Day 14 (Visit 4).
Population: 2 patients were enrolled in Triamcinolone acetonide arm and 3 patients were enrolled in Etanercept arm. However only two patients in the Etanercept arm completed the study. One patient completed only 2 study visits since the study was put on hold due to COVID-19 pandemic.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etanercept | Rescue Medication | Used Rescue Medications | 1 Participants |
| Etanercept | Rescue Medication | Did not use Rescue Medications | 1 Participants |
| Triamcinolone Acetonide | Rescue Medication | Used Rescue Medications | 2 Participants |
| Triamcinolone Acetonide | Rescue Medication | Did not use Rescue Medications | 1 Participants |
p-value: 0.05t-test, 2 sided
Secondary
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
Time frame: Day 1 (Baseline visit - Visit 1) through Day 30 (Safety follow up phone visit -Visit 5)
Population: 2 patients were enrolled in Triamcinolone acetonide arm and 3 patients were enrolled in Etanercept arm. However only two patients in the Etanercept arm completed the study. One patient completed only 2 study visits since the study was put on hold due to COVID-19 pandemic.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etanercept | Safety and Tolerability of Etanercept | Reported Adverse Events | 1 Participants |
| Etanercept | Safety and Tolerability of Etanercept | Did not report Adverse Events | 1 Participants |
| Triamcinolone Acetonide | Safety and Tolerability of Etanercept | Reported Adverse Events | 1 Participants |
| Triamcinolone Acetonide | Safety and Tolerability of Etanercept | Did not report Adverse Events | 2 Participants |
p-value: 0.05Chi-squared