PREventative Study Against URate-lowering Drug-induced Gout Exacerbations 1

Study Overview
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Brief Summary
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The purpose of this clinical research study was to determine the safety and effectiveness of an experimental drug called rilonacept in subjects with gout who are beginning allopurinol treatment for gout. Subjects will participate in this study for approximately 22 weeks. Rilonacept is being studied for use in preventing allopurinol-induced gout flares.

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Rilonacept for the Prophylaxis of Gout Flares During the Initiation of Allopurinol Therapy

Conditions
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Intercritical Gout

Intervention / Treatment
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* Other: Placebo
* Drug: Rilonacept 80 mg
* Drug: Rilonacept 160 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 to 80 years of age; Previously met the preliminary criteria of the American Rheumatism Association (ARA) for the classification; of the acute arthritis of primary gout; At least 2 gout flares in the year prior to the screening visit; Serum uric acid greater than or equal to 7.5 mg/dL at the screening visit; Exclusion Criteria: Acute gout flare within 2 weeks of the screening visit or during screening; Persistent chronic or active infections; History of an allergic reaction to allopurinol; History or presence of cancer within 5 years of the screening visit; Previous exposure to Rilonacept; Use of allopurinol, benzbromarone, febuxostat, probenecid or sulfinpyrazone within 3 months prior to the screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two subcutaneous injections of Placebo (for Rilonacept) as a loading dose on Day 1 followed by a single injection once a week (qw) from Week 1 to Week 15. | Other: Placebo<br>* Placebo loading dose followed by placebo injections (2 mL) qw for 16 weeks.<br>|
| Active Comparator: Rilonacept 80 mg<br>Two subcutaneous injections of Rilonacept 80 mg (for a total of 160 mg) as a loading dose on Day 1, followed by a single 80 mg injection of Rilonacept qw from Week 1 to Week 15. | Drug: Rilonacept 80 mg<br>* Rilonacept 160 mg loading dose followed by Rilonacept 80 mg/2 mL injections qw for 16 weeks.<br>|
| Active Comparator: Rilonacept 160 mg<br>Two subcutaneous injections of Rilonacept 160 mg (for a total of 320 mg) as a loading dose on Day 1, followed by a single 160 mg injection of Rilonacept qw from Week 1 to Week 15. | Drug: Rilonacept 160 mg<br>* Rilonacept 320 mg loading dose followed by Rilonacept 160 mg/2 mL injections qw for 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gout Flares Per Participant Assessed From Day 1 to Day 112 (Week 16) | A gout flare was defined as participant reported acute articular pain typical of a gout attack that required treatment with an anti-inflammatory therapeutic: had at least 3 of the following 4 signs or symptoms: joint swelling, tenderness, redness, and pain and with at least 1 of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. Number of gout flares per participant was reported for this outcome measure. For drop-outs, only flares occurred before Day 112 were counted, regardless whether the flares occurred during the treatment period or not. | Day 1 to Day 112 (Week 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Modified Gout Flares Per Participant From Day 1 to Day 112 (Week 16) | Modified gout flare was defined using modified definition of a gout flare as participant-reported articular pain typical of a gout attack that was deemed to require treatment with anti-inflammatory therapy. Number of modified gout flares per participant were reported for this outcome measure. | Day 1 to Day 112 (Week 16) | 
| Percentage of Participants With at Least One Gout Flare From Day 1 to Day 112 (Week 16) | Gout flare was defined as acute articular pain typical of a gout attack that required treatment with an anti-inflammatory therapeutic: had at least 3 of the following 4 signs or symptoms: joint swelling, tenderness, redness, and pain; and with at least 1 of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. Percentage of participants with at least one gout flare was reported for this outcome measure. | Day 1 to Day 112 (Week 16) | 
| Percentage of Participants With at Least Two Gout Flares From Day 1 to Day 112 (Week 16) | Gout flare was defined as acute articular pain typical of a gout attack that required treatment with an anti-inflammatory therapeutic: had at least 3 of the following 4 signs or symptoms: joint swelling, tenderness, redness, and pain, and with at least 1 of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. Percentage of participants with at least two gout flares was reported for this outcome measure. | Day 1 to Day 112 (Week 16) | 
| Number of Gout Flare Days Per Participant From Day 1 to Day 112 (Week 16) | Gout flare was defined as acute articular pain typical of a gout attack that required treatment with an anti-inflammatory therapeutic: had at least 3 of the following 4 signs or symptoms: joint swelling, tenderness, redness, and pain, and with at least 1 of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. Number of gout flare days per participant was reported for this outcome measure. | Day 1 to Day 112 (Week 16) | 
| Number of Gout Flare Days With Participant's Pain Score of 5 or More (From Daily Diary) Per Participant From Day 1 to Day 112 (Week 16) | Participants were asked to complete a telephone diary by calling the IVRS daily beginning at the baseline visit (Day 1) through the follow-up visit (Day 141) and reported their general well-being, gout symptoms, and weekly study drug administrations. At the onset of pain from a gout flare, participants were to answer additional diary questions regarding their gout flare and had to continue daily flare assessments until they reported the flare had ended. If a flare occurred just prior to the follow-up visit (Day 141), participants were to continue completing the daily diary until the flare resolved. Gout flare pain was assessed on a scale from 0 to 10 (with 0=no pain and 10=severe pain) within the past 24 hours. | Day 1 to Day 112 (Week 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism, Inborn Errors, Allopurinol, Metabolic Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Joint Diseases, Arthritis, Rheumatic Diseases, Metabolic disorder, Purine-Pyrimidine Metabolism, Inborn Errors, Gout