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

• ClinicalTrials.gov Identifier: NCT01362608
• Recruitment Status: Terminated
• First Posted: May 30, 2011
• Results First Posted: June 8, 2017
• Last Update Posted: June 8, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Gouty Arthritis	Drug: Canakinumab, ACZ885; Drug: Triamcinolone acetonide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 20, 2011
• Actual Primary Completion Date: May 19, 2015
• Actual Study Completion Date: May 19, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Canakinumab and placebo matching to triamcinolone acetonide; ACZ885H	Drug: Canakinumab, ACZ885; Canakinumab and placebo matching to triamcinolone acetonide
Active Comparator: Triamcinolone acetonide 40 mg; ACZ885H	Drug: Triamcinolone acetonide; Triamcinolone acetonide 40 mg and placebo matching to canakinumab

Outcome Measures

Primary Outcome Measures :

1. The Change in the Gout Pain Intensity in the Target Joint Following ACZ885 Administration Measured by Visual Analog Scale (VAS) [ Time Frame: at 72 hours post-dose ]
   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)
2. Time to First New Flare: Survival Analysis by Treatment: Kaplan Meier Analysis [ Time Frame: 12 weeks ]
   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

Secondary Outcome Measures :

1. The Number of Patients With at Least 1 New Gout Flare [ Time Frame: 12 weeks ]
2. Patients Assessment of Gout Pain Intensity in the Most Effected Joint (0-100mm VAS): Summary Statistics by Timepoint and Treatment [ Time Frame: baseline through 12 weeks ]
   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)
3. Patient's Assessment of Gout Pain Intensity in the Most Affected Joint (Likert Scale): Frequency Table by Timepoint and Treatment [ Time Frame: baseline through week 12 ]
   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).
4. Patient's Global Assessment of Response to Treatment: Frequency Table by Timepoint and Treatment Using a Likert Scale. [ Time Frame: 72 hours through week 12 ]
   Patients will score their response to pain on a 7-point Likert scale (excellent, good ,acceptable, slight,poor,very poor,not done).
5. Physician's Assessment of Tenderness: Frequency Table by Timepoint and Treatment [ Time Frame: baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose ]
   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).
6. Physician's Assessment of Swelling: Frequency Table by Timepoint and Treatment [ Time Frame: baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose ]
   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).
7. Physician's Assessment of Erythema: Frequency Table by Timepoint and Treatment [ Time Frame: baseline 72 hours,7 days 4 weeks, 8 weeks and 12 weeks post dose ]
   Physicians will score their response of erythema on a 4-point Likert scale (absent, present not assessed and not assessable).
8. Physician's Assessment of Range of Motion: Frequency Table by Timepoint and Treatment [ Time Frame: baseline through week 12 ]
   Physicians will score their response ofrange of motion on a 5-point Likert scale (normal,mildly restricted, moderately restricted, severely restricted and immolbilized).
9. Time to at Least a 50% Reduction in Baseline Pain Intensity: Survival Analysis by Treatment [ Time Frame: 12 weeks ]
   Kaplan Meier estimate
10. Time to Complete Resolution of Pain: Survival Analysis by Treatment [ Time Frame: 12 weeks ]
    Kaplan Meier estimate
11. Time to First Rescue Medication Intake [ Time Frame: 12 weeks ]
12. Percent Patients Who Took Rescue Medication [ Time Frame: 12 weeks ]
13. Amount of Rescue Medication Taken at Baseline Flare and Post Baseline Flare. [ Time Frame: 12 weeks ]
    Paracetamol / acetaminophen, Prednisolone and Prednisone taken at baseline flare and post baseline flare.
14. High Sensitivity C-reactive Protein [hsCRP] Measured in the Serum at 72 Hours Post Dose [ Time Frame: 72 hours post dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Argentina

Novartis Investigative Site

Ciudad Autonoma de Bs As, Argentina, C1015ABO

China, Anhui

Novartis Investigative Site

Hefei, Anhui, China, 230001

Novartis Investigative Site

Hefei, Anhui, China, 230022

China, Beijing

Novartis Investigative Site

Beijing, Beijing, China, 100730

China, Guangdong

Novartis Investigative Site

Guangzhou, Guangdong, China, 510080

China, Jiangsu

Novartis Investigative Site

Nanjing, Jiangsu, China, 210029

China, Shanxi

Novartis Investigative Site

Xi'an, Shanxi, China, 710032

China, Sichuan

Novartis Investigative Site

Chengdu, Sichuan, China, 610041

Novartis Investigative Site

Chengdu, Sichuan, China, 610072

China, Zhejiang

Novartis Investigative Site

Hangzhou, Zhejiang, China, 310009

China

Novartis Investigative Site

Beijing, China, 100029

Novartis Investigative Site

Beijing, China, 100044

Novartis Investigative Site

Shanghai, China, 200127

Novartis Investigative Site

Shanghai, China, 200433

Novartis Investigative Site

Wuhan, China, 430022

Poland

Novartis Investigative Site

Katowice, Poland, 40-084

Novartis Investigative Site

Poznan, Poland, 60-773

Novartis Investigative Site

Wroclaw, Poland, 50-349

Singapore

Novartis Investigative Site

Singapore, Singapore, 119074

Novartis Investigative Site

Singapore, Singapore, 529889

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01362608
• Other Study ID Numbers: CACZ885H2358; 2010-024172-26
• First Posted: May 30, 2011
• Results First Posted: June 8, 2017
• Last Update Posted: June 8, 2017
• Last Verified: June 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Gout; Inflammatory gout; acute gout

Additional relevant MeSH terms:

Arthritis, Gouty; Arthritis; Joint Diseases; Musculoskeletal Diseases; Gout; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action