Safety and Efficacy of Canakinumab Prefilled Syringes in Frequently Flaring Acute Gouty Arthritis Patients

Phase 3

Completed

• Conditions: Acute Gouty Arthritis
• Interventions: Drug: Canakinumab lyophilized powder; Drug: Canakinumab pre-filled syringe; Drug: Triamcinolone Acetonide; Drug: Placebo

• Registration Number: NCT01356602
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study assessed the safety and efficacy of canakinumab pre-filled syringes in comparison to triamcinolone acetonide 40 mg and canakinumab lyophilizate in patients that have frequent flares of acute gouty arthritis.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-05-16
• Study First Submitted QC: 2011-05-18
• Study First Posted: 2011-05-19
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Results First Submitted: 2013-09-06
• Status Verified: 2013-12
• Results First Submitted QC: 2013-12-10
• Last Update Submitted: 2013-12-10
• Results First Posted: 2014-01-29
• Last Update Posted: 2014-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 397

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Canakinumab, lyophilizate (LYO)	Canakinumab lyophilized powder	The patients on this arm received 150 mg s.c. at randomization and upon new flare. The doses were provided as lyophilized powder and had to be reconstituted with water for injection before application. The patients were given 3 injections: two placebo and one active drug.
Canakinumab, pre-filled syringes (PFS)	Canakinumab pre-filled syringe	Patients on this arm received 150 mg subcutaneously (s.c.) at randomization and upon new flare. The doses were provided as pre-filled syringes. The patients were given 3 injections: two placebo and one active drug.
Canakinumab, pre-filled syringes (PFS)	Placebo	Patients on this arm received 150 mg subcutaneously (s.c.) at randomization and upon new flare. The doses were provided as pre-filled syringes. The patients were given 3 injections: two placebo and one active drug.
Canakinumab, lyophilizate (LYO)	Placebo	The patients on this arm received 150 mg s.c. at randomization and upon new flare. The doses were provided as lyophilized powder and had to be reconstituted with water for injection before application. The patients were given 3 injections: two placebo and one active drug.
Triamcinolone Acetonide	Triamcinolone Acetonide	The patients on this arm received 40 mg intramuscular (i.m.) at randomization and upon new flare. The patients were given 3 injections: two placebo and one active drug.
Triamcinolone Acetonide	Placebo	The patients on this arm received 40 mg intramuscular (i.m.) at randomization and upon new flare. The patients were given 3 injections: two placebo and one active drug.

Primary Outcome Measures

Name	Time	Method
Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) Between the Canakinumab 150 mg PFS and Triamcinolone Acetonide 40 mg Groups	72 hours post dose	The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method.

Secondary Outcome Measures

Name	Time	Method
Pain Intensity on a 0 - 100 mm VAS Between the Canakinumab 150 mg PFS and Canakinumab 150 mg LYO Groups	72 hours post dose	The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method.
Patient's Assessment of Pain Intensity on a 0-100mm VAS	14 days	The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity VAS measurements up to 14 days.
Patient's Assessment of Pain Intensity on a 5-point Likert Scale	72 hours	A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their pain intensity in the most affected joint of the gout flare on a 5-point Likert scale (none, mild, moderate, severe, extreme). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity Likert measurements up to 14 days.
Number of Patients With at Least One New Gouty Arthritis Flare After Baseline	12 weeks	Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.
Time to the First New Gouty Arthritis Flare	12 weeks	Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. Less than 50% of patients had new flares. Therefore, the median time to new flare could not be calculated.
Time to 50% Reduction in Baseline Pain on a 0 - 100 VAS	14 days	The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Kaplan Meier estimate of time to 50% reduction in baseline pain, along with associated 95% confidence interval, were reported.
Time to Resolution of Gouty Arthritis Flare as Reported by Patient	14 days	Patients completed diary entries at 6, 12, 24, 48 and 72 hours post dose and then daily up to 7 days post-dose and/or daily until resolution of the flare. Kaplan Meier estimate of time to resolution of gouty flare as reported by patient, along with associated 95% confiedence interval, were reported.
Patient's Global Assessment of Response to Treatment on a 5-point Likert Scale	72 hours	A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their response to treatment on a 5-point Likert scale (excellent, good, acceptable, slight, poor). This outcome measure shows the number of patients indicating each score on the scale.
Physician's Global Assessment of Response to Treatment on a 5 Point Likert Scale	72 hours	A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Study physicians scored their assessment of the patients' response to treatment on a 5-point Likert scale (very good, good, fair, poor, very poor).
Physician's Assessment of Tenderness	72 hours	The study physician assessed the most affected joint for tenderness. Tenderness was measured on a 0 - 3 point scale as follows: 0 = no pain, 1 = patient states that "there is pain", 2 = patient states "there is pain and winces" and 3 = patient states "there is pain, winces and withdraws" on palpation or passive movement of the affected study joint.
Physician's Assessment of Swelling	72 hours	The study physician assessed the most affected joint for swelling. Swelling was measured on a 0 - 3 point scale as follows: 0 = no swelling, 1 = palpable, 2= visible and 3 = bulging beyond the joint margins.
Physician's Assessment of Erythema	72 hours	The study physician assessed the most affected joint for erythema. Erythema was assessed as present, absent or not assessable.
Physician's Assessment of Range of Motion of the Most Affected Joint	72 hours	The study physician assessed the patient's range of motion of the most affected joint on a 5 point Likert scale (normal, mildly restricted, moderately restricted, severely restricted and immobilized).
Time to First Rescue Medication Intake	14 days	Patients used a diary to record the time of intake of rescue medication and the amount taken.
Proportion of Patients With Rescue Medication Intake	12 weeks	Patients used a diary to record the time of intake of rescue medication and the amount taken.
Amount of Rescue Medication Taken (mg)	14 days	Patients used a diary to record the time of intake of rescue medication and the amount taken.
C-reactive Protein Level	72 hours	A central laboratory was used for analysis of all blood samples collected.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇱🇹 Vilnius, Lithuania