Acute Gouty Arthritis Flares
Conditions
Keywords
gouty arthritis
Brief summary
This was an 18-month, multi-center, open-label, clinical extension study. Patients completing earlier second extension studies (CACZ885H2356E2 and CACZ885H2357E2) continued to be treated in this combined extension 3 study for any new gouty arthritis flare on demand with one subcutaneous (s.c.) injection of canakinumab 150 mg.
Interventions
DRUGACZ885
canakinumab 150 mg s.c., given on demand upon new flares
Participants received 40 mg intramuscular (IM)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have completed the second extension studies CACZ885H2356E2 or CACZ885H2357E2 * Patients treated with canakinumab in the core studies or subsequent extensions
Exclusion criteria
\- Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | From start of the core studies (CACZ885H2357 [NCT01080131] and CACZ885H2361 [NCT01356602]) up to end of the current study (36 weeks) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline,or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of New Flares Per Participant | From start of the core studies (CACZ885H2357 [NCT01080131] and CACZ885H2361 [NCT01356602]) up to end of the current study (36 weeks) | Flare rate was calculated as the number of new flares over the period of observation in years. New flares occurred before first study medication dose in extension 3 study were considered. |
| Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | up to 7 days post-dose | Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none or mild). |
Countries
Australia, Canada, Estonia, Germany, Latvia, Lithuania, Russia, Ukraine, United States
Participant flow
Recruitment details
This study was conducted at 60 centers from 10-November-2011 (first participant first visit) to 22-May-2013 (last participant last visit).
Pre-assignment details
A total of 456 participants were randomized in the core studies (CACZ885H2356 and CACZ885H2357) of which 335 participants entered the first extension (CACZ885H2356E2) study. Out of the 317 participants who completed the first extension studies, 272 participants entered the second extension studies(CACZ885H2357E2 ). Out of the 249 participants who completed the second extension studies 136 participants entered the third extension study(CACZ885H2357E3).
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 150 mg Participants received 150 mg subcutaneously (S.C) at randomization and upon new flare. The doses were provided as pre-filled syringes. | 225 |
| Triamcinolone Acetonide 40 mg Participants received 40 mg Triamcinolone Acetonide intramuscular (IM) at randomization and upon new flare and re-treated with at least 1 dose of canakinumab. | 229 |
| Total | 454 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value | 1 | 1 |
| Overall Study | Administrative problems | 2 | 4 |
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Death | 2 | 2 |
| Overall Study | Lost to Follow-up | 18 | 13 |
| Overall Study | Participants did not entered extension studies 1, 2 and 3 | 103 | 136 |
| Overall Study | Protocol deviation | 1 | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 6 |
| Overall Study | Withdrawal by Subject | 19 | 17 |
Baseline characteristics
| Characteristic | Triamcinolone Acetonide 40 mg | Total | Canakinumab 150 mg |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 12.28 | 51.6 years STANDARD_DEVIATION 12.21 | 54.0 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized Asian | 9 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 24 Participants | 50 Participants | 26 Participants |
| Race/Ethnicity, Customized Caucasian | 96 Participants | 154 Participants | 74 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 7 Participants | 19 Participants | 12 Participants |
| Sex: Female, Male Male | 108 Participants | 209 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 225 | 2 / 229 |
| other Total, other adverse events | 87 / 225 | 55 / 229 |
| serious Total, serious adverse events | 35 / 225 | 23 / 229 |
Outcome results
Primary
Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline,or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time frame: From start of the core studies (CACZ885H2357 [NCT01080131] and CACZ885H2361 [NCT01356602]) up to end of the current study (36 weeks)
Population: The Safety Set consists of all participants that received study drug in the core study and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 150 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Adverse Events | 873 IR/100 patient-years |
| Canakinumab 150 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Non Fatal SAEs | 59 IR/100 patient-years |
| Canakinumab 150 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Death | 2 IR/100 patient-years |
| Triamcinolone Acetonide 40 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Death | 2 IR/100 patient-years |
| Triamcinolone Acetonide 40 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Adverse Events | 451 IR/100 patient-years |
| Triamcinolone Acetonide 40 mg | Number of Incidence Rate (IR) of Adverse Events, Serious Adverse Events and Death Per 100 Patient-years in Participants | Non Fatal SAEs | 25 IR/100 patient-years |
Secondary
Number of New Flares Per Participant
Flare rate was calculated as the number of new flares over the period of observation in years. New flares occurred before first study medication dose in extension 3 study were considered.
Time frame: From start of the core studies (CACZ885H2357 [NCT01080131] and CACZ885H2361 [NCT01356602]) up to end of the current study (36 weeks)
Population: Modified Analysis Set (MAS) consisted of all participants randomized in the core studies and received both treatments according to their exposure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab 150 mg | Number of New Flares Per Participant | 1.109 flares | Standard Deviation 1.608 |
| Triamcinolone Acetonide 40 mg | Number of New Flares Per Participant | 2.459 flares | Standard Deviation 3.701 |
Secondary
Patient's Assessment of Gout Pain Intensity in the Most Affected Joint
Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none or mild).
Time frame: up to 7 days post-dose
Population: Modified Analysis Set (MAS) consisted of all Full Analysis Set (FAS) participants. The FAS consisted of all enrolled participants who have received at least one dose of study medication. This outcome measure was assessed only in the subset of participants who had re-treatment with at least one dose of canakinumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | Baseline Flare | 102 Participants |
| Canakinumab 150 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | Last New Flare | 104 Participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | Baseline Flare | 72 Participants |
| Triamcinolone Acetonide 40 mg | Patient's Assessment of Gout Pain Intensity in the Most Affected Joint | Last New Flare | 69 Participants |