Safety & Efficacy of Canakinumab (ACZ885) in Patients With Frequent Flares for Whom Nonsterodial Anti-Inflammatory Drug (NSAIDs) and/ or Colchicine Are Contraindicated, Not Tolerated or Ineffective

Gouty Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Double-dummy, Active Controlled Study of Canakinumab (ACZ885) on the Treatment and Prevention of Gout Flares in Patients With Frequent Flares for Whom NSAIDs and/ or Colchicine Are Contraindicated, Not Tolerated or Ineffective

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01362608
• Other study ID #: CACZ885H2358
• Secondary ID: 2010-024172-26
• Status: Terminated
• Phase: Phase 3
• First received: May 24, 2011
• Last updated: June 7, 2017
• Start date: June 20, 2011
• Est. completion date: May 19, 2015

Study information

• Verified date: June 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this pivotal Phase III study is to support the registration of canakinumab for the indication of gout in China, a replicate of global studies CACZ885H2356 & CACZ885H2357 by demonstrating in patients with frequent flares of gout for whom NSAIDs and/or colchicine are contraindicated, not tolerated or ineffective, canakinumab 150 mg s.c. given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares compared to triamcinolone acetonide 40 mg i.m.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: May 19, 2015
• Est. primary completion date: May 19, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria:

• Meeting diagnosis criteria for acute arthritis of primary gout.

• Start of acute gout flare within 5 days prior to study visit 1

• History of = 3 gout flares within the 12 months prior to study start

• Evidence of contraindication (absolute or relative), or intolerance, or lack of efficacy for either NSAIDs and/or colchicines

Exclusion criteria:

• Requirement for administration of antibiotics against latent tuberculosis (TB), e.g., isoniazide

• Refractory heart failure (Stage D).

• Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia

• Secondary gout, chemotherapy induced gout, lead induced gout and transplant gout

• Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Arthritis, Gouty
• Gouty Arthritis

Intervention

Drug:
• Canakinumab, ACZ885
Canakinumab and placebo matching to triamcinolone acetonide
• Triamcinolone acetonide
Triamcinolone acetonide 40 mg and placebo matching to canakinumab

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Wuhan
China	Novartis Investigative Site	Xi'an	Shanxi
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  China,  Poland,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Change in the Gout Pain Intensity in the Target Joint Following ACZ885 Administration Measured by Visual Analog Scale (VAS)	A higher score indicates greater pain intensity. Based on the distribution of pain VAS scores in postsurgical patients (knee replacement, hysterectomy, or laparoscopic myomectomy) who described their postoperative pain intensity as none, mild, moderate, or severe, the following cut points on the pain VAS have been recommended: no pain (0 - 4 mm), mild pain (5- 44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm)	at 72 hours post-dose
Primary	Time to First New Flare: Survival Analysis by Treatment: Kaplan Meier Analysis	Measure canakinumab 150 mg s.c. is superior to triamcinolone acetonide 40 mg i.m. with respect to the time to the first new gout flare in observation period of 12 weeks	12 weeks
Secondary	The Number of Patients With at Least 1 New Gout Flare		12 weeks
Secondary	Patients Assessment of Gout Pain Intensity in the Most Effected Joint (0-100mm VAS): Summary Statistics by Timepoint and Treatment	A higher score indicates greater pain intensity. Based on the distribution of pain VAS scores in postsurgical patients (knee replacement, hysterectomy, or laparoscopic myomectomy) who described their postoperative pain intensity as none, mild, moderate, or severe, the following cut points on the pain VAS have been recommended: no pain (0 - 4 mm), mild pain (5- 44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm)	baseline through 12 weeks
Secondary	Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale): Frequency Table by Timepoint and Treatment	Patients will score their current pain intensity in the most affected joint of the gout flare on a 5-point Likert scale (none, mild, moderate, severe, extreme).	baseline through week 12
Secondary	Patient's Global Assessment of Response to Treatment: Frequency Table by Timepoint and Treatment Using a Likert Scale.	Patients will score their response to pain on a 7-point Likert scale (excellent, good ,acceptable, slight,poor,very poor,not done).	72 hours through week 12
Secondary	Physician's Assessment of Tenderness: Frequency Table by Timepoint and Treatment	Physicians will score their response to pain on a 5-point Likert scale (no pain, pain,pain and winces,pain winces and withdraws and not assessed).	baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose
Secondary	Physician's Assessment of Swelling: Frequency Table by Timepoint and Treatment	Physicians will score their response to pain on a 5-point Likert scale (no pain, pain,pain and winces,pain winces and withdraws and not assessed).	baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose
Secondary	Physician's Assessment of Erythema: Frequency Table by Timepoint and Treatment	Physicians will score their response of erythema on a 4-point Likert scale (absent, present not assessed and not assessable).	baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose
Secondary	Physician's Assessment of Range of Motion: Frequency Table by Timepoint and Treatment	Physicians will score their response ofrange of motion on a 5-point Likert scale (normal,mildly restricted, moderately restricted, severely restricted and immolbilized).	baseline through week 12
Secondary	Time to at Least a 50% Reduction in Baseline Pain Intensity: Survival Analysis by Treatment	Kaplan Meier estimate	12 weeks
Secondary	Time to Complete Resolution of Pain: Survival Analysis by Treatment	Kaplan Meier estimate	12 weeks
Secondary	Time to First Rescue Medication Intake		12 weeks
Secondary	Percent Patients Who Took Rescue Medication		12 weeks
Secondary	Amount of Rescue Medication Taken at Baseline Flare and Post Baseline Flare.	Paracetamol / acetaminophen, Prednisolone and Prednisone taken at baseline flare and post baseline flare.	12 weeks
Secondary	High Sensitivity C-reactive Protein [hsCRP] Measured in the Serum at 72 Hours Post Dose		72 hours post dose