A Study of the Efficacy of Canakinumab in Prevention of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy (Core Study) and a Long-term Study of the Efficacy and Safety of Canakinumab in Patients With Gout (Extension Study)

Gout Clinical Trial

Official title:

A 24-week, Dose-ranging, Multicenter, Double-blind, Double-dummy, Active-controlled Core Study to Evaluate Canakinumab for Prophylaxis of Signs and Symptoms of Acute Flares in Chronic Gout Patients Initiating Allopurinol Therapy and a 24-week Open-label, Multicenter Extension Study to Assess Safety, Tolerability and Efficacy of Canakinumab in Patients With Gout Who Are Given Canakinumab at the Time of Gout Flare

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00819585
• Other study ID #: CACZ885H2251
• Secondary ID: EudraCT : 2008-0
• Status: Completed
• Phase: Phase 2
• Start date: December 2008
• Est. completion date: August 2010

Study information

• Verified date: June 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The 24-week, dose-ranging, multi-center, double-blind, double-dummy, active-controlled core study investigated the prophylactic effect of canakinumab on the signs and symptoms of acute flares in chronic gout patients initiating allopurinol therapy. The core study was followed by a 24-week open-label, multicenter extension study to assess the safety, tolerability, and efficacy of canakinumab in patients with gout who were given canakinumab at the time of gout flare.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 432
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Core study

Inclusion Criteria:

• Signed written informed consent before any study procedure is performed.

• History of at least 2 gout flares in the year prior to Screening (Visit 1, based on patient history), thus, candidates for initiating uric acid lowering therapy.

• Confirmed diagnosis of gout meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of arthritis of primary gout.

• Body Mass Index (BMI) = 40 kg/m^2.

• Willingness to initiate allopurinol therapy as urate lowering agent for their gout therapy or having initiated allopurinol therapy within = 1 month before Screening (Visit 1) or willing to re-initiate allopurinol therapy if this was stopped > 2 months before Screening (Visit 1) for reasons different to toxicity/ intolerance or lack of efficacy.

Exclusion Criteria:

• Acute gout flare within 2 weeks of Screening (Visit 1) and during the Screening period.

• History of allergy or contraindication to colchicine or allopurinol.

• History of intolerance to allopurinol or to oral colchicine in appropriate dose for prophylactic use.

• History of bone marrow suppression.

• Absolute or relative contraindication to both naproxen and oral prednisolone/ prednisone.

Extension study

Inclusion criteria:

• Patients who completed the core study. A patient is defined as completing the core study if he/she completed the study up to and including the last visit (Visit 9).

• Patients who have signed a written informed consent before any trial procedure is performed.

Exclusion Criteria:

• Patients for whom continuation in the extension study is not considered appropriate by the treating physician.

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test (serum or urine).

Other protocol-defined inclusion/exclusion criteria applied to the study.

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• Canakinumab
Canakinumab was supplied in glass vials as a lyophilized powder.
• Colchicine
0.5 mg capsule orally once daily for 16 weeks.
• Allopurinol
100-300 mg orally once daily for 24 weeks.
• Placebo Matching Canakinumab
Subcutaneous injection.
• Placebo Matching Colchicine
Capsule orally once daily for 16 weeks.

Locations

Country	Name	City	State
Argentina	Novartis Investigative site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative site	Rosario
Belgium	Novartis Investigative Site	Gozée
Belgium	Novartis Investigative site	Oostham
Colombia	Novartis Investigative Site	Bacaramanga
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Fundación Cardiovascular de Colombia	Florida Blanca
Czechia	Novartis Investigative site	Havirov
Czechia	Novartis Investigative site	Ostrava
Czechia	Novartis Investigative site	Pardubice
Czechia	Novartis Investigative site	Uherske Hradiste
Czechia	Novartis Investigative site	Zlin
Germany	Novartis Investigative Site	Bautzen
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Georgensgmuend
Germany	Novartis Investigative Site	Goettingen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Messkirch
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Riedlhuette
Germany	Novartis Investigative Site	Schwabach
Guatemala	Novartis Investigative site	Guatemala City
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Zalaegerszeg
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative site	Coimbra
Portugal	Novartis Investigative site	Lisboa
Portugal	Novartis Investigative site	Ponte de Lima
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative site	Moscow
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Singapore	Novartis Investigative site	Singapore
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Piestany
Slovakia	Novartis Investigative Site	Povazska Bystrica
Slovakia	Novartis Investigative site	Trebisova
South Africa	Novartis Investigative site	Cape Town
South Africa	Novartis Investigative site	Panorama
South Africa	Novartis Investigative site	Port Elizabeth
Spain	Novartis Investigative Site	Barakaldo
Spain	Novartis Investigative site	Madrid
Spain	Novartis Investigative site	Merida
Spain	Novartis Investigative site	Valencia
Taiwan	Novartis Investigative site	Kaohsiung
Taiwan	Novartis Investigative site	Taichung
Taiwan	Novartis Investigative site	Taipei
Turkey	Baskent University Medical Faculty	Adana
Turkey	Baskent University Medical Faculty	Ankara
Turkey	Adnan Menderes University Medical Faculty	Aydin
Turkey	Cukurova University Medical Faculty	Balcali Adana
Turkey	Pamukkale University medical Faculty	Denizli Kampus
Turkey	Gaziantep University Medical Faculty	Gaziantep
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Celal Bayar University Medical Faculty	Manisa
United Kingdom	Gables Medicentre	Coventry
United Kingdom	Flyde Coast Clinical Research Ltd	Lancashire
United States	NM Clinical Research & Osteoporosis Ct.	Albuquerque	New Mexico
United States	Dolby Research, LLC	Baton Rouge	Louisiana
United States	Columbia Clinical Research	Columbia	South Carolina
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Upstate Pharmaceutical Research	Greenville	South Carolina
United States	East-West Medical Research institute	Honolulu	Hawaii
United States	Talbert Medical Group	Huntington Beach	California
United States	MultiSpecialty Clinical Research	Johnson City	Tennessee
United States	Health Awareness	Jupiter	Florida
United States	Health Research of Oklahoma, PLLC	Oklahoma City	Oklahoma
United States	Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Pinnacle Medical Research	Overland Park	Kansas
United States	Rochester clinical Research	Rochester	New York
United States	Shores Rheumatology	Saint Clair Shores	Michigan
United States	iMED Internal medicine, PA	San Antonio	Texas
United States	San Diego Arthritis & Osteoporosis Medical clinic	San Diego	California
United States	The Family Doctors	Shreveport	Louisiana
United States	Cotton O'Neil Clinical Research Institute	Topeka	Kansas
United States	Castlerock Clinical Research Consultants, LLC	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Colombia,  Czechia,  Germany,  Guatemala,  Hungary,  Poland,  Portugal,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Core Study: Mean Number of Gout Flares Per Participant	A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Baseline of the core study to Week 16
Secondary	Core Study: Mean Number of Gout Flares for the Repeat Dose Regimen of Canakinumab as Compared to the Single Doses of Canakinumab		up to 16 weeks after randomization
Secondary	Core Study: Percentage of Participants With at Least 1 Gout Flare Within 16 Weeks After Randomization	The percentage of participants experiencing at least 1 gout flare within 16 weeks after randomization. A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Baseline of the core study to Week 16
Secondary	Core Study: Percentage of Participants With Gout Flare at Different Time Points	A gout flare was defined as an increase in participant-reported gout pain in the most affected joint during a gout attack.	Days 2, 4, 6, and Weeks 2, 4, 6, 10, and 16 of the core study
Secondary	Core Study: Participant's Assessment of Gout Pain on a 0-100 mm Visual Analog Scale up to Day 7 of All Gout Flares	Participants rated the intensity of pain in the most affected joint on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.	Baseline of the core study to Week 16
Secondary	Core Study: Participant's Assessment of Gout Pain on a 5-point Likert Scale up to Day 7 of All Gout Flares	Participants assessed the intensity of pain in the most affected joint on a 5-point Likert scale, which ranged from 1 to 5 (1=None, 2=Mild, 3=Moderate, 4=Severe, 5=Extreme). Participants assessed pain intensity on the day of onset of the gout flare and in the morning of the 6 following days.	Baseline of the core study to Week 16
Secondary	Core Study: Physician's Global Assessment of Response to Therapy on a 5-point Likert Scale	The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at Days 15, 29, 57, 85, 113, and 141. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.	Days 15, 29, 57, 85, 113, and 141 of the core study
Secondary	Extension Study: Participant's Assessment of Gout Pain on a 100 mm Visual Analog Scale During the First Flare	Participant's rated the intensity of pain in the most affected joint during the first flare on a 0-100 mm visual analog scale, which ranged from no pain (left end, 0) to unbearable pain (right end, 100). Assessments were made pre-dose and 24 hours, 3 days, 4 days, and an average of 5-7 days post-dose	Baseline of the extension study until 7 days after the onset of the first gout flare (up to 24 weeks)
Secondary	Extension Study: Participant's Global Assessment of Response to Treatment on a 5-point Likert Scale	Study participants made a global assessment of their response to treatment on a 5-point Likert scale (Excellent, Good, Acceptable, Slight, Poor) at the control visit 7±2 days following each of their first 3 flares. The number of participants in each of the 5 categories of the Likert scale are reported.	Baseline of the extension study until the end of the study (up to 24 weeks)
Secondary	Extension Study: Physician's Global Assessment of Response to Treatment on a 5-point Likert Scale	The study physician made a global assessment of the participant's response to treatment on a 5-point Likert scale (Very good, Good, Fair, Poor, Very poor) at the control visit 7±2 days following each of the first 3 flares. The category 'Not assessed' includes missing data and 'not done'. The number of participants in each of the 5 categories of the Likert scale are reported.	Baseline of the extension study until the end of the study (up to 24 weeks)
Secondary	Extension Study: Physician's Assessment of Tenderness, Swelling, and Erythema in the Most Affected Joint During the First Flare	Tenderness was rated on a 0-3 point scale: 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 most affected joint. Swelling was rated on a 0-3 point scale: 0="no swelling", 1="palpable", 2="visible", and 3=bulging beyond the joint margins". Erythema was rated as present, absent, or not assessable. Assessments were performed at the flare and control visits.	Baseline of the extension study until the end of the study (up to 24 weeks)
Secondary	Extension Study: Amount of Rescue Medication Taken	The amount of naproxen and prednisolone taken after receiving treatment for each of the first 3 flares was recorded.	Baseline of the extension study until the end of the study (up to 24 weeks)