PREventative Study Against URate-lowering Drug-induced Gout Exacerbations 1 (PRE-SURGE1)

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

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.

Study Overview

• Status: Completed
• Conditions: Intercritical Gout
• Intervention / Treatment: Other: Placebo; Drug: Rilonacept 80 mg; Drug: Rilonacept 160 mg

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V3M7
  • Alberta
    • Calgary, Alberta, Canada, T2X3X7
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G1T4
    • Kamloops, British Columbia, Canada, V2C1K7
    • Kelowna, British Columbia, Canada, V1Y3G8
    • Quesnel, British Columbia, Canada, V2J2K3
    • Victoria, British Columbia, Canada, V8R 6V4
  • Newfoundland and Labrador
    • Mt. Pearl, Newfoundland and Labrador, Canada, A1N1W7
    • St. John's, Newfoundland and Labrador, Canada, A1E2E2
  • Ontario
    • Brampton, Ontario, Canada, L6W3E1
    • Corunna, Ontario, Canada, N0N1G0
    • Fort Erie, Ontario, Canada, L2A1Z3
    • Kitchener, Ontario, Canada, N2M5N6
    • Listowel, Ontario, Canada, N4W2P4
    • London, Ontario, Canada, N5Z3L2
    • London, Ontario, Canada, N6B2E5
    • Mississauga, Ontario, Canada, L5M2V8
    • Newmarket, Ontario, Canada, L3Y5G8
    • Sudbury, Ontario, Canada, P3E1H5
    • Toronto, Ontario, Canada, M9W4L6
    • Windsor, Ontario, Canada, N8X5A6
  • Quebec
    • Montreal, Quebec, Canada, H1T2M4
    • Trois-Rivieres, Quebec, Canada, G8Z1YZ
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K0H6
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Gilbert, Arizona, United States, 85296
    • Peoria, Arizona, United States, 85381
  • Arkansas
    • Searcy, Arkansas, United States, 72143
  • California
    • Concord, California, United States, 94520
    • San Diego, California, United States, 92103
    • Santa Maria, California, United States, 93454
  • Connecticut
    • Trumball, Connecticut, United States, 06611
  • District of Columbia
    • Washington, District of Columbia, United States, 20003
  • Florida
    • Daytona Beach, Florida, United States, 32117
    • Delray Beach, Florida, United States, 33446
    • Jacksonville, Florida, United States, 32205
    • Jupiter, Florida, United States, 33458
    • Naples, Florida, United States, 34102
    • St. Petersburg, Florida, United States, 33702
  • Georgia
    • Gainsville, Georgia, United States, 30501
    • Rome, Georgia, United States, 30165
    • Tucker, Georgia, United States, 30084
    • Woodstock, Georgia, United States, 30188
  • Idaho
    • Boise, Idaho, United States, 83713
  • Indiana
    • Avon, Indiana, United States, 46123
    • Evansville, Indiana, United States, 47714
    • South Bend, Indiana, United States, 46601
  • Kansas
    • Wichita, Kansas, United States, 67208
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
    • Owensboro, Kentucky, United States, 42303
  • Maryland
    • Baltimore, Maryland, United States, 21286
    • Ellicott City, Maryland, United States, 21042
    • Resistertown, Maryland, United States, 01136
  • Michigan
    • Troy, Michigan, United States, 48098
  • Mississippi
    • Jackson, Mississippi, United States, 39202
  • Missouri
    • Florissant, Missouri, United States, 63031
  • Nevada
    • Las Vegas, Nevada, United States, 89146
    • Las Vegas, Nevada, United States, 89123
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
    • Freehold, New Jersey, United States, 07728
  • New York
    • Brooklyn, New York, United States, 11201
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
    • Hickory, North Carolina, United States, 28601
    • Morehead City, North Carolina, United States, 28516
    • Raleigh, North Carolina, United States, 27607
    • Raleigh, North Carolina, United States, 27612
    • Salisbury, North Carolina, United States, 28144
  • Ohio
    • Akron, Ohio, United States, 44313
    • Cincinnati, Ohio, United States, 45246
    • Middleburg Heights, Ohio, United States, 44130
    • Perrysburg, Ohio, United States, 43551
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
    • Fountain Hill, Pennsylvania, United States, 18105
    • Huntingdon Valley, Pennsylvania, United States, 19006
    • Lancaster, Pennsylvania, United States, 17601
  • South Carolina
    • Charleston, South Carolina, United States, 29406
    • Columbia, South Carolina, United States, 29204
    • Greer, South Carolina, United States, 29651
    • North Charleston, South Carolina, United States, 29406
    • Rock Hill, South Carolina, United States, 29732
  • Tennessee
    • Memphis, Tennessee, United States, 38120
  • Texas
    • Dallas, Texas, United States, 75231
    • Dallas, Texas, United States, 75224
    • Houston, Texas, United States, 77074
    • Longview, Texas, United States, 75605
    • Richardson, Texas, United States, 75080
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Burke, Virginia, United States, 22015
    • Richmond, Virginia, United States, 23219
  • Washington
    • Spokane, Washington, United States, 99204
    • Tacoma, Washington, United States, 98405

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Placebo loading dose followed by placebo injections (2 mL) qw for 16 weeks.
Active Comparator: Rilonacept 80 mg; 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; Rilonacept 160 mg loading dose followed by Rilonacept 80 mg/2 mL injections qw for 16 weeks.
Active Comparator: Rilonacept 160 mg; 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; Rilonacept 320 mg loading dose followed by Rilonacept 160 mg/2 mL injections qw for 16 weeks.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Schumacher HR Jr, Evans RR, Saag KG, Clower J, Jennings W, Weinstein SP, Yancopoulos GD, Wang J, Terkeltaub R. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken). 2012 Oct;64(10):1462-70. doi: 10.1002/acr.21690.

Helpful Links

• Rilonacept
• Allopurinol
• Allopurinol sodium

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 23, 2009
• First Submitted That Met QC Criteria: January 26, 2009
• First Posted (Estimate): January 27, 2009

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Gout; Allopurinol; Genetic Diseases, Inborn; Metabolic Diseases; Metabolism, Inborn Errors; Metabolic disorder; Purine-Pyrimidine Metabolism, Inborn Errors
• 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; Anti-Inflammatory Agents; Rilonacept
• Other Study ID Numbers: IL1T-GA-0810