Gout
Conditions
Keywords
Intercritical Gout, 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 participants with gout who are beginning allopurinol treatment for gout. Participants will participate in this study for approximately 22 weeks. Rilonacept was being studied for use in preventing allopurinol-induced gout flares.
Interventions
DRUGPlacebo
Placebo loading dose followed by placebo subcutaneous (SC) injection (2 mL) once a week for 16 weeks.
DRUGRilonacept
Rilonacept 160 mg SC loading dose followed by Rilonacept 80 mg/2 mL SC injections once a week for 16 weeks.
Sponsors
Regeneron Pharmaceuticals
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
No
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 113 (Week 16) | Day 1 to Day 113 (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 flares per participant was reported for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Modified Gout Flares Per Participant From Day 1 to Day 113 (Week 16) | Day 1 to Day 113 (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 Flare From Day 1 to Day 113 (Week 16) | Day 1 to Day 113 (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 Flares From Day 1 to Day 113 (Week 16) | Day 1 to Day 113 (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 113 (Week 16) | Day 1 to Day 113 (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 113 (Week 16) | Day 1 to Day 113 (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
Germany, India, Indonesia, South Africa, Taiwan
Participant flow
Recruitment details
The study was conducted at 57 study sites in European Union (EU) and rest of world (ROW) between 7 March 2009 and 17 December 2010. A total of 471 participants were screened in the study.
Pre-assignment details
Out of 471 participants, 248 were randomized and treated in the study. Participants were randomized in 1:1:1 ratio to receive 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 once a week (qw) from Week 1 to Week 15. | 82 |
| 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. | 82 |
| 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. | 84 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 0 |
| Overall Study | Other than specified above | 2 | 3 | 2 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Rilonacept 80 mg | Rilonacept 160 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 51.7 years STANDARD_DEVIATION 12.87 | 52.6 years STANDARD_DEVIATION 11.47 | 49 years STANDARD_DEVIATION 11.77 | 51.1 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants | 82 Participants | 84 Participants | 248 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 | 29 Participants | 23 Participants | 30 Participants | 82 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 14 Participants | 10 Participants | 34 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 45 Participants | 44 Participants | 132 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 77 Participants | 77 Participants | 77 Participants | 231 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 | 12 / 82 | 20 / 82 | 20 / 84 |
| serious Total, serious adverse events | 4 / 82 | 5 / 82 | 3 / 84 |
Outcome results
Primary
Number of Gout Flares Per Participant Assessed From Day 1 to Day 113 (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 flares per participant was reported for this outcome measure.
Time frame: Day 1 to Day 113 (Week 16)
Population: Full analysis set (FAS) that included all randomized participants who received any study medication, and was based on the treatment allocated by the Interactive voice response system (IVRS) at randomization (as randomized). Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Gout Flares Per Participant Assessed From Day 1 to Day 113 (Week 16) | 1.23 Gout flares | Standard Deviation 1.57 |
| Rilonacept 80 mg | Number of Gout Flares Per Participant Assessed From Day 1 to Day 113 (Week 16) | 0.35 Gout flares | Standard Deviation 0.67 |
| Rilonacept 160 mg | Number of Gout Flares Per Participant Assessed From Day 1 to Day 113 (Week 16) | 0.34 Gout flares | Standard Deviation 0.86 |
Secondary
Number of Gout Flare Days Per Participant From Day 1 to Day 113 (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.
Time frame: Day 1 to Day 113 (Week 16)
Population: FAS that included all randomized participants who received any study medication, and was based on the treatment allocated by the IVRS at randomization (as randomized). Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Gout Flare Days Per Participant From Day 1 to Day 113 (Week 16) | 11.7 Gout flare days | Standard Deviation 21 |
| Rilonacept 80 mg | Number of Gout Flare Days Per Participant From Day 1 to Day 113 (Week 16) | 4.30 Gout flare days | Standard Deviation 17.13 |
| Rilonacept 160 mg | Number of Gout Flare Days Per Participant From Day 1 to Day 113 (Week 16) | 1.86 Gout flare days | Standard Deviation 5.8 |
Secondary
Number of Gout Flare Days With Participant's Pain Score of 5 or More (From Daily Diary) Per Participant From Day 1 to Day 113 (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.
Time frame: Day 1 to Day 113 (Week 16)
Population: FAS that included all randomized participants who received any study medication, and was based on the treatment allocated by IVRS at randomization (as randomized). Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Gout Flare Days With Participant's Pain Score of 5 or More (From Daily Diary) Per Participant From Day 1 to Day 113 (Week 16) | 4.28 Gout flare days | Standard Deviation 7.67 |
| Rilonacept 80 mg | Number of Gout Flare Days With Participant's Pain Score of 5 or More (From Daily Diary) Per Participant From Day 1 to Day 113 (Week 16) | 1.67 Gout flare days | Standard Deviation 8.43 |
| Rilonacept 160 mg | Number of Gout Flare Days With Participant's Pain Score of 5 or More (From Daily Diary) Per Participant From Day 1 to Day 113 (Week 16) | 0.88 Gout flare days | Standard Deviation 2.66 |
Secondary
Number of Modified Gout Flares Per Participant From Day 1 to Day 113 (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.
Time frame: Day 1 to Day 113 (Week 16)
Population: FAS that included all randomized participants who received any study medication, and was based on the treatment allocated by the IVRS at randomization (as randomized). Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Modified Gout Flares Per Participant From Day 1 to Day 113 (Week 16) | 1.51 Gout flares | Standard Deviation 1.87 |
| Rilonacept 80 mg | Number of Modified Gout Flares Per Participant From Day 1 to Day 113 (Week 16) | 0.62 Gout flares | Standard Deviation 1.32 |
| Rilonacept 160 mg | Number of Modified Gout Flares Per Participant From Day 1 to Day 113 (Week 16) | 0.48 Gout flares | Standard Deviation 0.99 |
Secondary
Percentage of Participants With at Least One Flare From Day 1 to Day 113 (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.
Time frame: Day 1 to Day 113 (Week 16)
Population: FAS that included all randomized participants who received any study medication, and was based on the treatment allocated by the IVRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least One Flare From Day 1 to Day 113 (Week 16) | 56.1 percentage of participants |
| Rilonacept 80 mg | Percentage of Participants With at Least One Flare From Day 1 to Day 113 (Week 16) | 25.6 percentage of participants |
| Rilonacept 160 mg | Percentage of Participants With at Least One Flare From Day 1 to Day 113 (Week 16) | 20.5 percentage of participants |
Secondary
Percentage of Participants With at Least Two Flares From Day 1 to Day 113 (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.
Time frame: Day 1 to Day 113 (Week 16)
Population: FAS that included all randomized participants who received any study medication, and was based on the treatment allocated by the IVRS at randomization (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least Two Flares From Day 1 to Day 113 (Week 16) | 32.9 percentage of participants |
| Rilonacept 80 mg | Percentage of Participants With at Least Two Flares From Day 1 to Day 113 (Week 16) | 8.5 percentage of participants |
| Rilonacept 160 mg | Percentage of Participants With at Least Two Flares From Day 1 to Day 113 (Week 16) | 6.0 percentage of participants |