Trial Outcomes & Findings for Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients (NCT NCT00798369)

NCT ID: NCT00798369

Last Updated: 2012-04-10

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 200 participants
• Primary outcome timeframe: at 24,48 and 72 hours post-baseline
• Results posted on: 2012-04-10

Participant Flow

Participant milestones

Measure	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.	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.	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.	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.	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.	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.
Overall Study STARTED	28	29	29	29	28	57
Overall Study COMPLETED	27	28	27	28	27	54
Overall Study NOT COMPLETED	1	1	2	1	1	3

Reasons for withdrawal

Measure	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.	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.	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.	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.	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.	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.
Overall Study Subject withdrew consent	0	0	1	1	0	2
Overall Study Lost to Follow-up	1	1	1	0	1	0
Overall Study Adminstrative problems	0	0	0	0	0	1

Baseline Characteristics

Targeted Dose Finding of Canakinumab (ACZ885) for Management of Acute Flare in Refractory or Contraindicated Gout Patients

Baseline characteristics by cohort

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=29 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=28 Participants 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.	Triamcinolone Acetonide 40 mg n=57 Participants 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.	Total n=200 Participants Total of all reporting groups
Age, Customized ≥18 years - 40 years	6 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	5 participants n=4 Participants	8 participants n=21 Participants	7 participants n=8 Participants	33 participants n=8 Participants
Age, Customized ≥ 41 - 64 years	21 participants n=5 Participants	21 participants n=7 Participants	19 participants n=5 Participants	20 participants n=4 Participants	15 participants n=21 Participants	39 participants n=8 Participants	135 participants n=8 Participants
Age, Customized ≥ 65 - 74 years	0 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants	10 participants n=8 Participants	24 participants n=8 Participants
Age, Customized ≥ 75 years	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants	1 participants n=8 Participants	8 participants n=8 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	14 Participants n=8 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	26 Participants n=7 Participants	27 Participants n=5 Participants	24 Participants n=4 Participants	28 Participants n=21 Participants	55 Participants n=8 Participants	186 Participants n=8 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Canakinumab 10 mg n=197 Participants 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.	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.	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.	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.	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.	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.
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 Interval 5.94 to 103.37	—	—	—	—	—
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 Interval 2.87 to 96.31	—	—	—	—	—
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 A target dose for canakinumab to be comparable to triamcinolone acetonide 40 mg could not be estimated at 72 hours as it lies below the range of all doses of canakinumab tested in this trial	—	—	—	—	—

SECONDARY outcome

Timeframe: 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

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).

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
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	-46.6 Units on a scale Standard Error 4.39	-48.6 Units on a scale Standard Error 4.56	-52.7 Units on a scale Standard Error 4.35	-62.5 Units on a scale Standard Error 4.58	-43.3 Units on a scale Standard Error 3.16
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	-53.9 Units on a scale Standard Error 3.93	-63.4 Units on a scale Standard Error 4.00	-61.2 Units on a scale Standard Error 3.96	-66.4 Units on a scale Standard Error 4.19	-56.0 Units on a scale Standard Error 2.88

SECONDARY outcome

Timeframe: 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.

Participants scored their global assessment of response to treatment using a 5-point Likert scale: Excellent, Good, Acceptable, Slight and Poor.

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
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	62 Percentage of Participants	71 Percentage of Participants	66 Percentage of Participants	89 Percentage of Participants	54 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
The Time to 50% Reduction of Baseline Pain Intensity in the Target Joint	2.9 Days Interval 1.0 to 4.0	2.9 Days Interval 2.0 to 3.0	1.0 Days Interval 1.0 to 2.9	1.0 Days Interval 1.0 to 2.0	1.0 Days Interval 0.5 to 2.0	2.0 Days Interval 1.0 to 3.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
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	2.0 mg/L Standard Error 1.72	2.6 mg/L Standard Error 1.75	5.2 mg/L Standard Error 1.72	2.9 mg/L Standard Error 1.75	8.6 mg/L Standard Error 1.24
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	7.9 mg/L Standard Error 3.34	11.7 mg/L Standard Error 3.49	13.4 mg/L Standard Error 3.34	9.2 mg/L Standard Error 3.53	13.4 mg/L Standard Error 2.43
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 3.30	2.5 mg/L Standard Error 3.23	4.3 mg/L Standard Error 3.31	6.3 mg/L Standard Error 3.29	3.7 mg/L Standard Error 3.36	13.7 mg/L Standard Error 2.35
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	2.9 mg/L Standard Error 3.08	2.9 mg/L Standard Error 3.14	4.8 mg/L Standard Error 3.08	4.8 mg/L Standard Error 3.13	9.2 mg/L Standard Error 2.20

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
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	27.6 mg/L Standard Error 19.32	70.7 mg/L Standard Error 19.37	29.4 mg/L Standard Error 19.28	26.9 mg/L Standard Error 19.69	52.5 mg/L Standard Error 14.48
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	4.6 mg/L Standard Error 3.64	5.7 mg/L Standard Error 3.64	8.2 mg/L Standard Error 3.56	4.1 mg/L Standard Error 3.57	18.0 mg/L Standard Error 2.68
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	5.4 mg/L Standard Error 10.91	11.9 mg/L Standard Error 10.94	10.5 mg/L Standard Error 10.89	10.3 mg/L Standard Error 11.33	39.4 mg/L Standard Error 8.26
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	4.2 mg/L Standard Error 3.46	4.9 mg/L Standard Error 3.53	14.3 mg/L Standard Error 3.45	6.2 mg/L Standard Error 3.53	12.9 mg/L Standard Error 2.59

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Canakinumab 10 mg n=28 Participants 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.	Canakinumab 25 mg n=29 Participants 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.	Canakinumab 50 mg n=28 Participants 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.	Canakinumab 90 mg n=29 Participants 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.	Canakinumab 150 mg n=27 Participants 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.	Triamcinolone Acetonide 40 mg n=56 Participants 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.
Amount of Rescue Medication Taken for Each Treatment Group Acetaminophen	1414.3 mg Standard Deviation 2628.58	1656.9 mg Standard Deviation 4437.26	2178.6 mg Standard Deviation 2925.67	1646.6 mg Standard Deviation 3161.20	607.4 mg Standard Deviation 2250.12	1614.3 mg Standard Deviation 2958.51
Amount of Rescue Medication Taken for Each Treatment Group Codeine	42.9 mg Standard Deviation 138.19	78.6 mg Standard Deviation 164.20	49.3 mg Standard Deviation 139.57	27.9 mg Standard Deviation 87.07	4.4 mg Standard Deviation 23.09	52.0 mg Standard Deviation 158.28
Amount of Rescue Medication Taken for Each Treatment Group Prednisolone/Prednisone	13.4 mg Standard Deviation 36.82	23.8 mg Standard Deviation 44.03	24.1 mg Standard Deviation 59.36	13.1 mg Standard Deviation 35.37	6.2 mg Standard Deviation 24.54	13.3 mg Standard Deviation 26.13

Adverse Events

Canakinumab 10 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Canakinumab 25 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Canakinumab 50 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Canakinumab 90 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Canakinumab 150 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Triamcinolone Acetonide 40 mg

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Canakinumab 10 mg n=28 participants at risk 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.	Canakinumab 25 mg n=29 participants at risk 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.	Canakinumab 50 mg n=29 participants at risk 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.	Canakinumab 90 mg n=29 participants at risk 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.	Canakinumab 150 mg n=28 participants at risk 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.	Triamcinolone Acetonide 40 mg n=57 participants at risk 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.
Infections and infestations Appendicitis	0.00% 0/28 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Infections and infestations Bronchitis	0.00% 0/28 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Nervous system disorders Carotid artery stenosis	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Nervous system disorders Cerebrovascular disorder	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	1.8% 1/57 • End of study (8 weeks)

Other adverse events

Measure	Canakinumab 10 mg n=28 participants at risk 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.	Canakinumab 25 mg n=29 participants at risk 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.	Canakinumab 50 mg n=29 participants at risk 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.	Canakinumab 90 mg n=29 participants at risk 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.	Canakinumab 150 mg n=28 participants at risk 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.	Triamcinolone Acetonide 40 mg n=57 participants at risk 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.
Infections and infestations Nasopharyngitis	3.6% 1/28 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	3.6% 1/28 • End of study (8 weeks)	3.5% 2/57 • End of study (8 weeks)
Infections and infestations Urinary tract infection	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	5.3% 3/57 • End of study (8 weeks)
Investigations Alanine aminotransferase increased	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Investigations Aspartate aminotransferase increased	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	3.6% 1/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Investigations Blood uric acid increased	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	3.6% 1/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/28 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	5.3% 3/57 • End of study (8 weeks)
Nervous system disorders Headache	3.6% 1/28 • End of study (8 weeks)	10.3% 3/29 • End of study (8 weeks)	3.4% 1/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	3.6% 1/28 • End of study (8 weeks)	7.0% 4/57 • End of study (8 weeks)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/28 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	3.6% 1/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/28 • End of study (8 weeks)	6.9% 2/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/29 • End of study (8 weeks)	0.00% 0/28 • End of study (8 weeks)	0.00% 0/57 • End of study (8 weeks)

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER