Acute Gout
Conditions
Keywords
Acute flares, Gout, Anti-interleukin-1β monoclonal antibody, Colchicine, Triamcinolone acetonide
Brief summary
This 8-week study is designed to determine the target dose of canakinumab (ACZ885) for the management of acute flare in gout patients who are contraindicated to Non-Steroidal anti-inflammatory drugs and/or colchicine. The efficacy of ACZ885 will be compared to the corticosteroid triamcinolone acetonide.
Interventions
DRUGCanakinumab
Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once, on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle.
DRUGTriamcinolone acetonide
Randomized patients received triamcinolone acetonide 40 mg i.m. once and placebo matching canakinumab s.c. once, on Day 1.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* History of at least 1 gout flare prior to the Screening Visit * Meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout. * Presence of acute gout flare for no longer than 5 days. * Baseline pain intensity \> or = to 50 mm on the 0-100 mm VAS. * Contraindicated for, intolerant or unresponsive to NSAIDs, colchicine or both.
Exclusion criteria
* Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis. * Presence of severe renal function impairment * Contraindication to intramuscular injection * Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment * Evidence of active pulmonary disease * Live vaccinations within 3 months prior to the start of the study * Use of forbidden therapy Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) | at 24,48 and 72 hours post-baseline | Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | at 72 hours post-baseline | Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor. |
| The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | Baseline, within 7 days after randomization | The median time in days to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). |
| The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | Baseline,at 72 hrs post-dose and 7 days post-dose | The change in pain intensity from baseline to 72 hours and 7 days post dose as measured on a 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain. Analysis of Covariance (ANCOVA) with treatment group, VAS at baseline and Body mass Index (BMI) at baseline as covariates. Change from baseline = (post-baseline measurement - baseline). |
| Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | at 72 hours and 7 days, 4 and 8 weeks post-dose | Serum amyloid A (SAA) were determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates. |
| Amount of Rescue Medication Taken for Each Treatment Group | 7 days after study drug administration | Participants who had difficulty in tolerating their pain after the 6-hour post-dose pain assessments and during the first 7 study days were allowed to take a maximum of 30 mg prednisolone (or equivalent dose of prednisone \[30 mg\]) orally once a day for a maximum of 5 days. In addition, participants could use 500 mg acetaminophen (paracetamol) and/or 30 mg codeine as needed during the first 7 study days. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/dose or 180 mg/day of codeine was allowed during the first 7 days of the study. |
| High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | at 72 hours and 7 days, 4 and 8 weeks post-dose | High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates. |
Countries
Argentina, Belgium, Canada, France, Germany, Poland, Russia, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab 10 mg Canakinumab 10 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle. | 28 |
| Canakinumab 25 mg Canakinumab 25 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle. | 29 |
| Canakinumab 50 mg Canakinumab 50 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle. | 29 |
| Canakinumab 90 mg Canakinumab 90 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle. | 29 |
| Canakinumab 150 mg Canakinumab 150 mg subcutaneous (s.c) once. The s.c. injection could be administered into the arm or thigh. Randomized patients received one s.c. injection of canakinumab and placebo matching triamcinolone acetonide (0.9% sodium chloride) intramuscularly (i.m.) once,on Day 1. The i.m. injection was recommended to be administered deeply into the gluteal muscle. | 28 |
| Triamcinolone Acetonide 40 mg Triamcinolone acetonide 40 mg intramuscularly (i.m) once. The i.m. injection was recommended to be administered deeply into the gluteal muscle. Randomized patients received triamcinolone acetonide 40 mg i.m. once or canakinumab matching placebo once, on Day 1. | 57 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adminstrative problems | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Subject withdrew consent | 0 | 0 | 1 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Canakinumab 10 mg | Canakinumab 25 mg | Canakinumab 50 mg | Canakinumab 90 mg | Canakinumab 150 mg | Triamcinolone Acetonide 40 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized ≥18 years - 40 years | 6 participants | 4 participants | 3 participants | 5 participants | 8 participants | 7 participants | 33 participants |
| Age, Customized ≥ 41 - 64 years | 21 participants | 21 participants | 19 participants | 20 participants | 15 participants | 39 participants | 135 participants |
| Age, Customized ≥ 65 - 74 years | 0 participants | 3 participants | 6 participants | 2 participants | 3 participants | 10 participants | 24 participants |
| Age, Customized ≥ 75 years | 1 participants | 1 participants | 1 participants | 2 participants | 2 participants | 1 participants | 8 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 0 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 27 Participants | 24 Participants | 28 Participants | 55 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 28 | 7 / 29 | 5 / 29 | 8 / 29 | 5 / 28 | 8 / 57 |
| serious Total, serious adverse events | 0 / 28 | 2 / 29 | 2 / 29 | 0 / 29 | 0 / 28 | 1 / 57 |
Outcome results
Primary
The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS)
Mean target dose at 24, 48 and 72 hours. Four models: Emax, Logistic, Linear in log-dose, Linear were selected to describe the potential dose-response curve and hence estimate the target dose of canakinumab using baseline Visual Analog Scale (VAS) and Body Mass Index (BMI) as covariates. Target dose was defined as the dose for which the efficacy is equivalent to the efficacy of triamcinolone acetonide 40 mg and was identified by assessing the dose response relationship with regards to the pain intensity in the target joint measured on a 0- 100 mm VAS (0= no pain and 100= unbearable pain).
Time frame: at 24,48 and 72 hours post-baseline
Population: The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Canakinumab 10 mg | The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) | Target dose at 24 hrs post-baseline | 37 mg |
| Canakinumab 10 mg | The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) | Target dose at 48 hrs post-baseline | 23 mg |
| Canakinumab 10 mg | The Dose of Canakinumab for Treatment of Acute Flares in Gout Patients That Leads to the Same Efficacy as Triamcinolone Acetonide With Respect to Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) | Target dose at 72 hrs post-baseline | NA mg |
Secondary
Amount of Rescue Medication Taken for Each Treatment Group
Participants who had difficulty in tolerating their pain after the 6-hour post-dose pain assessments and during the first 7 study days were allowed to take a maximum of 30 mg prednisolone (or equivalent dose of prednisone \[30 mg\]) orally once a day for a maximum of 5 days. In addition, participants could use 500 mg acetaminophen (paracetamol) and/or 30 mg codeine as needed during the first 7 study days. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/dose or 180 mg/day of codeine was allowed during the first 7 days of the study.
Time frame: 7 days after study drug administration
Population: The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 10 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 1414.3 mg | Standard Deviation 2628.58 |
| Canakinumab 10 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 13.4 mg | Standard Deviation 36.82 |
| Canakinumab 10 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 42.9 mg | Standard Deviation 138.19 |
| Canakinumab 25 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 23.8 mg | Standard Deviation 44.03 |
| Canakinumab 25 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 78.6 mg | Standard Deviation 164.2 |
| Canakinumab 25 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 1656.9 mg | Standard Deviation 4437.26 |
| Canakinumab 50 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 24.1 mg | Standard Deviation 59.36 |
| Canakinumab 50 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 49.3 mg | Standard Deviation 139.57 |
| Canakinumab 50 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 2178.6 mg | Standard Deviation 2925.67 |
| Canakinumab 90 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 1646.6 mg | Standard Deviation 3161.2 |
| Canakinumab 90 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 27.9 mg | Standard Deviation 87.07 |
| Canakinumab 90 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 13.1 mg | Standard Deviation 35.37 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 4.4 mg | Standard Deviation 23.09 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 607.4 mg | Standard Deviation 2250.12 |
| Canakinumab 150 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 6.2 mg | Standard Deviation 24.54 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken for Each Treatment Group | Prednisolone/Prednisone | 13.3 mg | Standard Deviation 26.13 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken for Each Treatment Group | Acetaminophen | 1614.3 mg | Standard Deviation 2958.51 |
| Triamcinolone Acetonide 40 mg | Amount of Rescue Medication Taken for Each Treatment Group | Codeine | 52.0 mg | Standard Deviation 158.28 |
Secondary
High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
High sensitivity C-reactive protein (hsCRP) was determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Time frame: at 72 hours and 7 days, 4 and 8 weeks post-dose
Population: The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 10 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 16.7 mg/L | Standard Error 3.41 |
| Canakinumab 10 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 3.8 mg/L | Standard Error 1.79 |
| Canakinumab 10 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 8.0 mg/L | Standard Error 3.3 |
| Canakinumab 10 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 3.0 mg/L | Standard Error 3.13 |
| Canakinumab 25 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 2.5 mg/L | Standard Error 3.23 |
| Canakinumab 25 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 7.9 mg/L | Standard Error 3.34 |
| Canakinumab 25 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 2.9 mg/L | Standard Error 3.08 |
| Canakinumab 25 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 2.0 mg/L | Standard Error 1.72 |
| Canakinumab 50 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 11.7 mg/L | Standard Error 3.49 |
| Canakinumab 50 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 2.6 mg/L | Standard Error 1.75 |
| Canakinumab 50 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 2.9 mg/L | Standard Error 3.14 |
| Canakinumab 50 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 4.3 mg/L | Standard Error 3.31 |
| Canakinumab 90 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 13.4 mg/L | Standard Error 3.34 |
| Canakinumab 90 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 4.8 mg/L | Standard Error 3.08 |
| Canakinumab 90 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 6.3 mg/L | Standard Error 3.29 |
| Canakinumab 90 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 5.2 mg/L | Standard Error 1.72 |
| Canakinumab 150 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 3.7 mg/L | Standard Error 3.36 |
| Canakinumab 150 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 9.2 mg/L | Standard Error 3.53 |
| Canakinumab 150 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 2.9 mg/L | Standard Error 1.75 |
| Canakinumab 150 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 4.8 mg/L | Standard Error 3.13 |
| Triamcinolone Acetonide 40 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 27, 28, 26, 28, 25, 53) | 13.4 mg/L | Standard Error 2.43 |
| Triamcinolone Acetonide 40 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 28, 27, 28, 27, 54) | 8.6 mg/L | Standard Error 1.24 |
| Triamcinolone Acetonide 40 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 55) | 9.2 mg/L | Standard Error 2.2 |
| Triamcinolone Acetonide 40 mg | High Sensitivity C-reactive Protein (hsCRP) at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 29, 28, 28, 27, 55) | 13.7 mg/L | Standard Error 2.35 |
Secondary
Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment
Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.
Time frame: at 72 hours post-baseline
Population: The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Canakinumab 10 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 64 Percentage of Participants |
| Canakinumab 25 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 62 Percentage of Participants |
| Canakinumab 50 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 71 Percentage of Participants |
| Canakinumab 90 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 66 Percentage of Participants |
| Canakinumab 150 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 89 Percentage of Participants |
| Triamcinolone Acetonide 40 mg | Percentage of Participants With an Excellent or Good Response With Regards to the Patient's Global Assessment of Response to Treatment | 54 Percentage of Participants |
Secondary
Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group
Serum amyloid A (SAA) were determined in serum at all visits (Visits 1-5) in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. ANCOVA with treatment group, protein level at baseline and BMI at baseline as covariates.
Time frame: at 72 hours and 7 days, 4 and 8 weeks post-dose
Population: The Full Analysis Set (FAS) consisted of all patients as randomized that had at least one post-baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 10 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 10.6 mg/L | Standard Error 10.92 |
| Canakinumab 10 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 50.1 mg/L | Standard Error 20.05 |
| Canakinumab 10 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 4.4 mg/L | Standard Error 3.53 |
| Canakinumab 10 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 5.5 mg/L | Standard Error 3.64 |
| Canakinumab 25 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 4.6 mg/L | Standard Error 3.64 |
| Canakinumab 25 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 4.2 mg/L | Standard Error 3.46 |
| Canakinumab 25 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 27.6 mg/L | Standard Error 19.32 |
| Canakinumab 25 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 5.4 mg/L | Standard Error 10.91 |
| Canakinumab 50 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 4.9 mg/L | Standard Error 3.53 |
| Canakinumab 50 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 70.7 mg/L | Standard Error 19.37 |
| Canakinumab 50 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 5.7 mg/L | Standard Error 3.64 |
| Canakinumab 50 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 11.9 mg/L | Standard Error 10.94 |
| Canakinumab 90 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 14.3 mg/L | Standard Error 3.45 |
| Canakinumab 90 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 8.2 mg/L | Standard Error 3.56 |
| Canakinumab 90 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 10.5 mg/L | Standard Error 10.89 |
| Canakinumab 90 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 29.4 mg/L | Standard Error 19.28 |
| Canakinumab 150 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 4.1 mg/L | Standard Error 3.57 |
| Canakinumab 150 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 26.9 mg/L | Standard Error 19.69 |
| Canakinumab 150 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 10.3 mg/L | Standard Error 11.33 |
| Canakinumab 150 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 6.2 mg/L | Standard Error 3.53 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 72 hrs post-dose (n= 26, 28, 28, 28, 27, 50) | 52.5 mg/L | Standard Error 14.48 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 4 week post-dose (n= 27, 28, 27, 28, 27, 50) | 12.9 mg/L | Standard Error 2.59 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 8 weeks post-dose (n= 26, 26, 26, 27, 27, 48) | 18.0 mg/L | Standard Error 2.68 |
| Triamcinolone Acetonide 40 mg | Serum Amyloid Protein (SAA) Levels at 72 Hours, 7days, 4 Weeks and 8 Weeks Post Dose for Each Treatment Group | 7 days post-dose (n= 28, 28, 28, 28, 26, 49) | 39.4 mg/L | Standard Error 8.26 |
Secondary
The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide
The change in pain intensity from baseline to 72 hours and 7 days post dose as measured on a 0-100 mm Visual Analog Scale(VAS): 0= no pain and 100= severe pain. Analysis of Covariance (ANCOVA) with treatment group, VAS at baseline and Body mass Index (BMI) at baseline as covariates. Change from baseline = (post-baseline measurement - baseline).
Time frame: Baseline,at 72 hrs post-dose and 7 days post-dose
Population: Full Analysis Set consisting of all participants with data for baseline and the given time point for each arm/group. Assessments up to Day 8, with 1 missing pain intensity value had it imputed. LOCF method was applied to impute post-dose measurements. Missing baseline values were replaced by the median baseline assessment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Canakinumab 10 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -57.6 Units on a scale | Standard Error 4.06 |
| Canakinumab 10 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -48.6 Units on a scale | Standard Error 4.36 |
| Canakinumab 25 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -46.6 Units on a scale | Standard Error 4.39 |
| Canakinumab 25 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -53.9 Units on a scale | Standard Error 3.93 |
| Canakinumab 50 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -63.4 Units on a scale | Standard Error 4 |
| Canakinumab 50 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -48.6 Units on a scale | Standard Error 4.56 |
| Canakinumab 90 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -52.7 Units on a scale | Standard Error 4.35 |
| Canakinumab 90 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -61.2 Units on a scale | Standard Error 3.96 |
| Canakinumab 150 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -62.5 Units on a scale | Standard Error 4.58 |
| Canakinumab 150 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -66.4 Units on a scale | Standard Error 4.19 |
| Triamcinolone Acetonide 40 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 72 hrs post-dose (n= 28, 28, 26, 28, 27, 53) | -43.3 Units on a scale | Standard Error 3.16 |
| Triamcinolone Acetonide 40 mg | The Change in Pain Intensity in the Target Joint Following Canakinumab Administration Compared to Triamcinolone Acetonide | 7 days post-dose (n= 26, 28, 27, 27, 26, 51) | -56.0 Units on a scale | Standard Error 2.88 |
Secondary
The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint
The median time in days to at least 50% reduction in Pain intensity from baseline as measured by Visual Analog Scale (VAS) for each treatment group. Participants scored their pain intensity in the target joint on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100).
Time frame: Baseline, within 7 days after randomization
Population: The Full Analysis Set (FAS) consisted of all participants as randomized that had at least one post baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, participants were analyzed according to the treatment they were assigned to at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Canakinumab 10 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 2.9 Days |
| Canakinumab 25 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 2.9 Days |
| Canakinumab 50 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 1.0 Days |
| Canakinumab 90 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 1.0 Days |
| Canakinumab 150 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 1.0 Days |
| Triamcinolone Acetonide 40 mg | The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint | 2.0 Days |