| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of acute gouty arthritis flares in frequently flaring patients |
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| E.1.1.1 | Medical condition in easily understood language |
| Gout is a type of arthritis with recurrent attacks that causes the joints,often the big toe to be red, hot,swollen and tender.It is caused by build-up of uric acid crystals in the body |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10018627 |
| E.1.2 | Term | Gout |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To confirm that canakinumab 150 mg s.c. administered as pre-filled syringe (PFS) is superior to triamcinolone acetonide 40 mg i.m with respect to patient’s assessment of acute gouty arthritis pain intensity in the joint most affected at randomization measured after 72 hours (on a 0-100 mm VAS)
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| E.2.2 | Secondary objectives of the trial |
To evaluate treatment comparisons a) canakinumab PFS vs. triamcinolone acetonide and b) canakinumab PFS vs. canakinumab LYO
• Percentage of patients with at least 1 new gouty arthritis flare
• Time to first new gouty arthritis flare
Efficacy with respect to the treatment of signs and symptoms of the baseline acute gouty arthritis flare defined as:
• Time to 50% reduction of acute gouty arthritis pain intensity (VAS) in the joint most affected at randomization
• Time to resolution of acute gouty arthritis flare as reported by the patient
• Patient’s assessment of acute gouty arthritis pain intensity in the most affected joint (on a 0-100 mm VAS) over time, during the flare
• Patient’s assessment of acute gouty arthritis pain intensity in the most affected joint (Likert scale) over time, during the flare
• Patient’s global assessment of response to treatment (Likert scale) over time, during the flare
please refer to the protocol |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
At screening:
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. History of ≥ 3 gout flares within the previous 12 months (based on patient history, referral letter and/or patient interview)
5. Evidence of contraindication (absolute or relative), or intolerance, or lack of efficacy for:
• NSAIDs and/or
• colchicine BMI ≤ 45 kg/m2
Additional criteria at randomization:
1. If on urate lowering therapy (e.g. allopurinol), patient should be receiving a stable dose and schedule with no changes in therapy for 2 weeks prior to randomization
2. Onset of current acute gouty arthritis flare within 3 days prior to randomization
3. Patient’s assessment of gouty arthritis pain intensity in the most affected joint of ≥ 50 mm on the 0-100 mm VAS
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| E.4 | Principal exclusion criteria |
1. Use of the following therapies:
Corticosteroids:
• A dose of ≥ 10 mg of prednisolone or equivalent within 24 hours prior to randomization 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 prior to randomization
• Intra-muscular corticosteroids for any indication within 14 days prior to randomization
Narcotics (opiates and tramadol) within 24 hours prior to randomization
Topical ice/cold packs within 6 hours prior to randomization
Chronic opiate treatment within 14 days prior to randomization
Any IL-1 blocker, TNF inhibitor, other biologic or investigational drug within 30 days or 5 half-lives prior to randomization, whichever is longer, or as instructed by local regulations
NSAIDs (including Cox-2 inhibitors), and other pain medication as defined below:
• Any ibuprofen within 4 hours before randomization (Day 1) or > 400 mg within 8 hours prior to randomization (i.e. 0-400 mg ibuprofen allowed between 4-8 hours prior to randomization)
• Any acetaminophen (paracetamol) within 4 hours prior to randomization or > 1 g within 24 hours prior to randomization
• Any aspirin within 4 hours prior to randomization or > 600 mg within 24 hours prior to randomization
• Over-the-counter analgesic aspirin-based or paracetamol-based combination medications: any number of tablets within 4 hours before randomization or > 2 tablets within 24 hours prior to randomization
• Diclofenac: any diclofenac within 8 hours prior to randomization or > 50 mg within 24 hours before randomization
• Naproxen: any naproxen within 12 hours prior to randomization or > 500 mg within 24 hours before randomization
• Cox-2 inhibitors within 48 hours prior to randomization
• Other NSAIDs within 24 hours prior to randomization
Colchicine > 1.2 mg within 24 hours prior to randomization
2. Hemodialysis
3. Live vaccinations within 3 months prior to randomization
4. Donation or loss of 400 mL or more of blood in the 12 weeks prior to randomization
5. Secondary gout (e.g. chemotherapy induced gout, lead induced gout, transplant gout, etc.)
6. Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
7. 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)
8. Presence of idiopathic thrombocytopenic purpura
9. Any conditions or significant medical problems which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for immunomodulatory therapy, or
• Any active or recurrent bacterial, fungal or viral infection at the time of randomization, where an IL-1 blocker might have an impact on an underlying severe, immunocompromised disease state
• Presence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B or Hepatitis C infections based on screening lab results
• Presence of tuberculosis (TB) established during screening, if there are signs of tuberculosis it should be confirmed as inactive and that adequate treatment was completed and successful prior to randomization
• Requirement for administration of antibiotics against latent tuberculosis e.g., isoniazide (courses of antibiotic therapy started prior to entering the study should not be prematurely terminated to allow inclusion into the study)
please refer to the protocol
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| This trial has been designed to show superior efficacy for canakinumab 150 mg PFS compared to triamcinolone acetonide 40 mg with respect to pain intensity at 72 hours post dose. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint for the trial is at pain at 72 Hours post dose. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| Canada |
| Germany |
| Hungary |
| Lithuania |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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