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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00829829

Acronym

PRE-SURGE1

Enrollment

241

Registered

2009-01-27

Start date

2009-02-28

Completion date

2010-06-30

Last updated

2017-04-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Intercritical Gout

Keywords

Metabolism, Inborn Errors, Allopurinol, Metabolic Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Joint Diseases, Arthritis, Rheumatic Diseases, Metabolic disorder, Purine-Pyrimidine Metabolism, Inborn Errors, Gout

Brief summary

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.

Interventions

OTHERPlacebo

Placebo loading dose followed by placebo injections (2 mL) qw for 16 weeks.

DRUGRilonacept 80 mg

Rilonacept 160 mg loading dose followed by Rilonacept 80 mg/2 mL injections qw for 16 weeks.

DRUGRilonacept 160 mg

Rilonacept 320 mg loading dose followed by Rilonacept 160 mg/2 mL injections qw for 16 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Gout Flares Per Participant Assessed From Day 1 to Day 112 (Week 16)	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.

Secondary

Measure	Time frame	Description
Number of Modified Gout Flares Per Participant From Day 1 to Day 112 (Week 16)	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.
Percentage of Participants With at Least One Gout Flare From Day 1 to Day 112 (Week 16)	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.
Percentage of Participants With at Least Two Gout Flares From Day 1 to Day 112 (Week 16)	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.
Number of Gout Flare Days Per Participant From Day 1 to Day 112 (Week 16)	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.
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)	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.

Countries

Canada, United States

Participant flow

Recruitment details

The study was conducted at 49 study sites in Unites States (US) and 15 study sites in Canada between 5 March 2009 and 18 May 2010. A total of 468 participants were screened in the study.

Pre-assignment details

Out of 468 participants, 241 were randomized and 240 treated in the study. Participants were randomized in 1:1:1 ratio to receive either Placebo or Rilonacept 80 mg or Rilonacept 160 mg.

Participants by arm

Arm	Count
Placebo Two subcutaneous injections of Placebo (for Rilonacept ) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15.	79
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.	80
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.	81
Total	240

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	4	4	3
Overall Study	Decision by the Sponsor	1	0	2
Overall Study	Lost to Follow-up	7	3	3
Overall Study	Other than specified above	2	2	1
Overall Study	Protocol Violation	0	3	0
Overall Study	Withdrawal by Subject	8	4	2

Baseline characteristics

Characteristic	Placebo	Rilonacept 80 mg	Rilonacept 160 mg	Total
Age, Continuous	52.2 years STANDARD_DEVIATION 13.6	52.9 years STANDARD_DEVIATION 12.5	51.9 years STANDARD_DEVIATION 11.6	52.3 years STANDARD_DEVIATION 12.6
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	2 Participants	2 Participants	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants	78 Participants	79 Participants	234 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	4 Participants	5 Participants	1 Participants	10 Participants
Race (NIH/OMB) Black or African American	11 Participants	15 Participants	10 Participants	36 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	64 Participants	60 Participants	69 Participants	193 Participants
Sex: Female, Male Female	3 Participants	9 Participants	5 Participants	17 Participants
Sex: Female, Male Male	76 Participants	71 Participants	76 Participants	223 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	8 / 79	16 / 80	17 / 81
serious Total, serious adverse events	3 / 79	3 / 80	3 / 81

Outcome results

Primary

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.