A randomized, controlled study of ACZ885 (canakinumab) 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 - H2357

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-017802-35-LV
• Date of registration: 30/03/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, controlled study of ACZ885 (canakinumab) 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 - H2357
• Scientific title: A randomized, controlled study of ACZ885 (canakinumab) 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 - H2357
• Date of first enrolment: 07/05/2010
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017802-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Estonia, Latvia, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent before any study procedure is performed.
2. Male or female patients aged = 18 - = 85 years
3. Meeting the ACR 1977 preliminary criteria for the classification of acute arthritis of primary gout.
4. Onset of current acute gout flare within 5 days prior to randomization.
5. Patient’s assessment of baseline pain intensity = 50 mm on the 0-100 mm VAS.
6. History of = 3 gout flares within the 12 months prior to randomization (based on patient history, referral letter and/ or patient interview).
7. Evidence of contraindication (absolute or relative), or intolerance, or lack of efficacy for:
a. NSAIDs (based on medical history, referral letter, and/ or patient interview)
and/or
b. colchicine (based on medical history, referral letter, and/ or patient interview). Note if a patient resides in a country where colchicine is not available or not considered standard medical practice for treating signs and symptoms of gout flares above criterion #a must be met.
8. If on urate lowering therapy (e.g. allopurinol, febuxostat, pegloticase, probenecid) and/or on prophylactic low-dose colchicine, stable dose and schedule with no changes in therapy for 2 weeks prior to randomization and expected to remain on a stable regimen during study participation.
9. BMI = 45 kg/m2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Use of the following therapies:
a. Corticosteroids:
• A dose of = 10mg of prednisolone or equivalent within 24 hours before screening for any indication.
• Chronic corticosteroid treatment (defined as a prednisolone dose of = 5 mg/ day or equivalent taken for > 28 days)
• Intra-articular corticosteroids into the most affected joint within 14 days before screening
• Intra-muscular corticosteroids for any indication within 14 days before screening.
b. Narcotics (opiates and tramadol) within 24 hours prior to randomization
c. NSAIDs (including Cox-2 inhibitors), and othe pain medications as defined below:
• Any Acetaminophen (paracetamol) within 4 hours prior to screening or > 1g within 24 hours before screening
• Ibuprofen: any ibuprofen within 4 hours before screening (Day 1) or
> 400 mg within 8 hours before screening (i.e. 0-400 mg ibuprofen allowed between 4-8 hours before screening)
• Aspirin: any aspirin within 4 hours before screening or > 600 mg within 24 hours before screening
• Over-the-counter analgesic aspirin-based or paracetamol-based combination medications: any number of tablets within 4 hours before screening or
> 2 tablets within 24 hours before screening
• Diclofenac: any diclofenac within 8 hours before screening or
> 50 mg within 24 hours before screening
• Naproxen: any naproxen within 12 hours before screening or
> 500 mg within 24 hours before screening
• Cox-2 inhibitors within 48 hours before screening
• Other NSAIDs within 24 hours before screening
d. Colchicine: > 1.2 mg within 24 before screening
e. Topical ice/ cold packs within 6 hours prior to randomization
f. Chronic opiate treatment within 14 days prior to randomization
g. Any IL-1 blocker, TNF inhibitor, other biologic or investigational drug within 30 days or 5 half-lives before randomization, whichever is longer, or as instructed by local regulations.
2. Hemodialysis
3. Live vaccinations within 3 months prior to randomization.
4. Donation or loss of 400 mL or more of blood in the 8 weeks prior to randomization.
5. Requirement for administration of antibiotics against latent tuberculosis (TB), e.g., isoniazide (courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study).
6. Refractory heart failure (Stage D). Patients for whom electrical device therapy is indicated (e.g. history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia, with LVEF <35%) are excluded from the study.
7. Unstable cardiac arrhythmias or unstable symptomatic coronary ischemia
8. Secondary gout (e.g. chemotherapy induced gout, lead induced gout, transplant gout, etc.)
9. Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis.
10. History of hypersensitivity to the study drugs or to molecules with similar structures, or contraindication to intramuscular injection (e.g. patients on anticoagulants, thrombocytopenia, known hemostasis disease).
11. Presence of idiopathic thrombocytopenic purpura.
12. Known presence or suspicion of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infections (based on history and/or clinical findings) or any active or recurrent bacterial, fungal or viral infection at the time of enrollment, where an IL-1 blocker might have an impact on an underlying severe, immunocompromised disease state.
13. One of the risk factors for TB such as but not limit

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment and prevention of gout flares in patients with frequent flares for whom NSAIDs and/ or colchicine are contraindicated, not tolerated or ineffective
MedDRA version: 12.1 Level: LLT Classification code 10018627 Term: Gout

Intervention(s)

Trade Name: ILARIS
Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Other descriptive name: Recombinant human monoclonal antibody to human IL-1Beta of the IgG1/K class
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Kenalog 40mg/ml injection for
suspension
Product Name: Triamcinolone acetonide
Pharmaceutical Form: Suspension for injection
CAS Number: 76-25-5
Other descriptive name: TRIAMCINOLONE ACETONIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Emulsion for infusion
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Secondary Objective: • To evaluate the percentage of patients with at least 1 new gout flare during 12 weeks
• To evaluate the efficacy of canakinumab 150 mg s.c. compared to triamcinolone acetonide 40 mg i.m. with respect to the treatment of signs and symptoms of each acute gout flare, defined as:
• Patient’s assessment of gout pain intensity in the most affected joint (on a 0-100 mm VAS) over time
• Patient’s assessment of gout pain intensity in the most affected joint (Likert scale) over time
• Patient’s global assessment of response to treatment (Likert scale) over time
• Physician’s assessment of tenderness, swelling and erythema over time
• Physician’s assessment of range of motion of the most affected joint (Likert scale) over time
• Physician’s global assessment of response to treatment (Likert scale) over time
• To evaluate the time to 50% reduction of baseline pain intensity in the most affected joint[...]

Main Objective: The two co-primary objectives of this study are:
• To confirm that canakinumab 150 mg s.c. is superior to triamcinolone acetonide 40 mg i.m. with respect to patient’s assessment of gout pain intensity in the most affected joint at 72 hours post-dose (on a 0-100mm VAS)
• To confirm that 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

Primary end point(s): The two co-primary endpoints of this study are:
• To confirm that canakinumab 150 mg s.c. is superior to triamcinolone acetonide 40 mg i.m. with respect to patient’s assessment of gout pain intensity in the most affected joint at 72 hours post-dose (on a 0-100mm VAS)
• To confirm that 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

Secondary ID(s)

2009-017802-35-NL

CACZ885H2357