E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment and prevention of gout flares in patients with frequent flares for whom NSAIDs and/ or colchicine are contraindicated, not tolerated or ineffective |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
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 |
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 in observation period of 12 weeks Both co-primary objectives have to be met. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: • 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 baseline 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 [...] please refer to the protocol |
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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: 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 defined as (based on medical history, referral letter, and/ or patient interview)and/or b. colchicine (based on medical history, referral letter, and/ or patient interview) 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. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 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 more than 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 before screening c. NSAIDs (including Cox-2 inhibitors) and other pain medication as defined below: • Any acetaminophen (paracetamol) within 4 hours before screening or > 1 g 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 hours before screening e. Topical ice/ cold packs within 6 hours before screening f. Chronic opiate treatment within 14 days before screening 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. h. Herbal therapy treatment taken orally for gout indication one month before screening. Topical herbal therapy packs 6 hours before screening. i. Acupuncture treatment for gout indication one month before screening 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 chemotherapy induced gout, lead induced gout and transplant gout. 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 limited or exclusive to: a. History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or noninjection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or b. Close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease within the last 12 months. 14. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection determined as defined by local guidelines/ local medical practice (see also Section 6.2.2). If presence of tuberculosis is established then treatment (according to local guidelines) must have been completed prior to randomization. [...] please refer to the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 in observation period of 12 weeks |
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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.8.3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 22 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 22 |