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

Acute Gouty Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Active-controlled Study of Canakinumab Prefilled Syringes or Reconstituted Lyophilizate Versus Triamcinolone Acetonide for Treating Acute Gouty Arthritis Flares in Frequently Flaring Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01356602
• Other study ID #: CACZ885H2361
• Secondary ID: 2010-024173-39
• Status: Completed
• Phase: Phase 3
• First received: May 16, 2011
• Last updated: December 10, 2013
• Start date: May 2011
• Est. completion date: September 2012

Study information

• Verified date: December 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesHungary: Institutional Ethics CommitteeLithuania: State Medicine Control Agency - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria:

• 3 or more gout flares within last year

• Contraindication, intolerance or lack of efficacy for NSAIDs and/or colchicine

• Body mass index of less than or equal to 45 kg/m2

Exclusion criteria:

• Use of the following therapies (within varying protocol defined timeframes):

corticosteroids, narcotics, topical ice/cold packs, chronic opiate treatment, NSAIDs (such as aspirin), colchicine.

• Hemodialysis

• Live vaccine within 3 months before first dose

• Donation or loss of 400 mL or more within 3 months before first dose

• Gout brought on by other factors such as chemotherapy, lead, transplant, etc.

• Presence of other acute inflammatory arthritis such as Rheumatoid Arthritis

• Any conditions or significant medical problems that puts the patient at an unacceptable immunological risk to receive this type of therapy such as HIV, Hepatitis, Tuberculosis and other infections/conditions

• Significant cardiovascular conditions such as uncontrolled hypertension

• Significant medical diseases such as uncontrolled diabetes, thyroid disease

• History of malignancy of any organ system within the past 5 years

• Women who are pregnant or nursing

• Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Gouty Arthritis
• Arthritis
• Arthritis, Gouty

Intervention

Drug:
• Canakinumab pre-filled syringe
Canakinumab pre-filled syringe
• Canakinumab lyophilized powder
Canakinumab lyophilized powder
• Triamcinolone Acetonide
Triamcinolone Acetonide
• Placebo
Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	St-John's	Newfoundland and Labrador
Canada	Novartis Investigative Site	St. John	Newfoundland and Labrador
Canada	Novartis Investigative Site	Toronto	Ontario
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Loehne
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Messkirch
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Weener
Germany	Novartis Investigative Site	Zwiesel
Hungary	Novartis Investigative Site	Bekescsaba
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Szikszo
Hungary	Novartis Investigative Site	Szolnok
Hungary	Novartis Investigative Site	Veszprem
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius	LT
United States	Novartis Investigative Site	Anniston	Alabama
United States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Augusta	Georgia
United States	Novartis Investigative Site	Bedford	Texas
United States	Novartis Investigative Site	Bellevue	Washington
United States	Novartis Investigative Site	Belzoni	Mississippi
United States	Novartis Investigative Site	Bountiful	Utah
United States	Novartis Investigative Site	Bristol	Tennessee
United States	Novartis Investigative Site	Buena Park	California
United States	Novartis Investigative Site	Cary	North Carolina
United States	Novartis Investigative Site	Chandler	Arizona
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Danville	Virginia
United States	Novartis Investigative Site	Decatur	Georgia
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Fair Oaks	California
United States	Novartis Investigative Site	Fargo	North Dakota
United States	Novartis Investigative Site	Fayetteville	Tennessee
United States	Novartis Investigative Site	Freehold	New Jersey
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greer	South Carolina
United States	Novartis Investigative Site	Gulf Shores	Alabama
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Johnson City	Tennessee
United States	Novartis Investigative Site	Jupiter	Florida
United States	Novartis Investigative Site	Largo	Florida
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Memphis	Tennessee
United States	Novartis Investigative Site	Meridian	Idaho
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Midlothian	Virginia
United States	Novartis Investigative Site	Mineola	New York
United States	Novartis Investigative Site	Missoula	Montana
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Mogadore	Ohio
United States	Novartis Investigative Site	Murrells Inlet	South Carolina
United States	Novartis Investigative Site	New Hyde Park	New York
United States	Novartis Investigative Site	Newport News	Virginia
United States	Novartis Investigative Site	Ninety Six	South Carolina
United States	Novartis Investigative Site	Norwalk	California
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orangevale	California
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Owensboro	Kentucky
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Picayune	Mississippi
United States	Novartis Investigative Site	Roslyn	New York
United States	Novartis Investigative Site	Salisbury	North Carolina
United States	Novartis Investigative Site	Scottsdale	Arizona
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Troy	Michigan
United States	Novartis Investigative Site	Varnville	South Carolina
United States	Novartis Investigative Site	Westlake Village	California
United States	Novartis Investigative Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hungary,  Lithuania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) Between the Canakinumab 150 mg PFS and Triamcinolone Acetonide 40 mg Groups	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.	72 hours post dose	No
Secondary	Pain Intensity on a 0 - 100 mm VAS Between the Canakinumab 150 mg PFS and Canakinumab 150 mg LYO Groups	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.	72 hours post dose	No
Secondary	Patient's Assessment of Pain Intensity on a 0-100mm VAS	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.	14 days	No
Secondary	Patient's Assessment of Pain Intensity on a 5-point Likert Scale	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.	72 hours	No
Secondary	Number of Patients With at Least One New Gouty Arthritis Flare After Baseline	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.	12 weeks	No
Secondary	Time to the First New Gouty Arthritis Flare	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.	12 weeks	No
Secondary	Time to 50% Reduction in Baseline Pain on a 0 - 100 VAS	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.	14 days	No
Secondary	Time to Resolution of Gouty Arthritis Flare as Reported by Patient	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.	14 days	No
Secondary	Patient's Global Assessment of Response to Treatment on a 5-point Likert Scale	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.	72 hours	No
Secondary	Physician's Global Assessment of Response to Treatment on a 5 Point Likert Scale	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).	72 hours	No
Secondary	Physician's Assessment of Tenderness	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.	72 hours	No
Secondary	Physician's Assessment of Swelling	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.	72 hours	No
Secondary	Physician's Assessment of Erythema	The study physician assessed the most affected joint for erythema. Erythema was assessed as present, absent or not assessable.	72 hours	No
Secondary	Physician's Assessment of Range of Motion of the Most Affected Joint	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).	72 hours	No
Secondary	Proportion of Patients With Rescue Medication Intake	Patients used a diary to record the time of intake of rescue medication and the amount taken.	12 weeks	No
Secondary	Time to First Rescue Medication Intake	Patients used a diary to record the time of intake of rescue medication and the amount taken.	14 days	No
Secondary	Amount of Rescue Medication Taken (mg)	Patients used a diary to record the time of intake of rescue medication and the amount taken.	14 days	No
Secondary	C-reactive Protein Level	A central laboratory was used for analysis of all blood samples collected.	72 hours	No