E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute gout (patients who are refractory or contraindicated to NSAIDs and/or colchicine) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018628 |
E.1.2 | Term | Gout acute |
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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 primary objective is to determine the target dose of canakinumab for the treatment of acute flares in gout patients who are refractory or contraindicated to NSAIDs and/or colchicine. The target dose is the dose that leads to the same efficacy as the comparator and will be identified by assessing the dose response relationship of various doses of canakinumab with regards to the pain intensity in the target joint at 72 hours (Day 4) post-dose measured on a 0-100 mm Visual Analog Scale (VAS). |
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E.2.2 | Secondary objectives of the trial |
Change in pain intensity in the target joint following canakinumab vs triamcinolone acetonide on a 0-100 mm VAS at 6, 12, 24, 48, 72 and hours 4, 5, 6 and 7 days post-dose.
Change in pain intensity in the target joint following canakinumab vs triamcinolone acetonide via a 5-point Likert scale at 6, 12, 24, 48, 72 hours and 4, 5, 6 and 7 days post-dose.
Efficacy of canakinumab as compared to triamcinolone acetonide with regards to
- Patient’s global assessment of response to treatment at 72 hours and 7 days post-dose,
- Time to 50% reduction of baseline pain intensity in the target joint,
- hsCRP and SAA protein levels at 72 hours, 7 days, 4 and 8 weeks post-dose,
- Amount of rescue medication taken,
- Time to first rescue medication intake,
- Time to first recurrence of acute gout flare after study drug administration.
Safety, tolerability and immunogenicity following single administration of canakinumab (at different doses).
PK/PD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Signed written informed consent before any study procedure is performed. Male or female patients aged ≥ 18 - ≤ 80 years.
History of at least 1 gout flare prior to the Screening Visit (based on patient history). Meeting the ACR 1977 preliminary criteria for the classification of acute arthritis of primary gout.
Presence of acute gout flare for no longer than 5 days.
Baseline pain intensity ≥ 50 mm on the 0-100 mm VAS.
Refractory (previous unsatisfactory outcome) to NSAID and/or colchicine use OR Absolutely or relatively contraindicated (e.g. due to co-morbidities such as kidney insufficiency, type 2 diabetes, gastrointestinal intolerance or other reasons) to NSAID and/or colchicine use.
Patients on urate lowering therapy (e.g. allopurinol, probenecid) or on prophylactic colchicine must be on a stable dose and schedule with no changes in therapy for 4 weeks prior to randomization and expected to remain on a stable regimen during study participation.
Patients with a BMI ≤ 40 kg/m2. |
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E.4 | Principal exclusion criteria |
Ibuprofen within 4 hours before screening (Day 1) or > 400 mg within 8 hours before screening.
Paracetamol within 4 hours before screening or > 1 g within 24 hours before screening.
Aspirin within 4 hours before screening or > 600 mg within 24 hours before screening.
Aspirin- or paracetamol-based combination medications: any number of tablets within 4 hours before screening or > 2 tablets within 24 hours before screening.
Diclofenac within 8 hours before screening or > 50 mg within 24 hours before screening.
Naproxen within 12 hours before screening or > 500 mg within 24 hours before screening.
Cox-2 inhibitors within 48 hours before screening.
NSAIDs within 24 hours before screening.
Systemic corticosteroids within 24 hours before screening (dose < 10 mg of prednisolone or equivalent is permissible within 24 hours before screening).
I.A. corticosteroids within 4 weeks before screening.
More than 1 single dose of 0.6 mg colchicine within 24 hours before screening, if not on stable dose and regimen.
Anakinra therapy within 24 hours before screening.
Rilonacept within 1 week before screening.
Investigational medicinal products other than anakinra or rilonacept, within 30 days (or 3 months for mAbs) or 5 half-lives before screening, whichever is longer or instructed by local regulations.
TNF inhibitors within the past 3 months prior to randomization
Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis.
Severe renal function impairment. History of renal trauma, glomerulonephritis, patients with one kidney, or renal failure requiring regular dialysis treatments.
History of clinically significant drug allergy. History of hypersensitivity to the study drug or to molecules with similar structures.
Presence of idiopathic thrombocytopenic purpura.
Contraindication to intramuscular injection.
Donation or loss of 400 mL or more of blood in the 8 weeks before dosing.
Live vaccinations within 3 months prior to the start of the study. Killed or inactivated vaccines may be permitted according to the investigator’s discretion.
Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of HIV infection, Hep B and Hep C infections.
Evidence of active pulmonary disease (e.g. tuberculosis, fungal diseases).
Requirement for administration of antibiotics against latent TB, e.g., isoniazide.
One of the risk factors for TB such as:
History of any of the following: residence in a congregate setting, substance abuse, 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 close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period) with a person with active pulmonary TB disease.
Any surgical or underlying hepatic, hematologic, pulmonary, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunodulatory therapy.
Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at screening or baseline.
Significant medical problems, including but not limited to the following: uncontrolled hypertension (≥ 200/105 mmHg), CHF [NYHA IV], uncontrolled diabetes type I and II (recent blood glucose > 300 mg/dL), thyroid disease (unless the patient is taking a stable dose of thyroid hormone or anti-thyroid medications for at least 12 weeks), which in the opinion of the Investigator will exclude the patient from the study.
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence of metastases.
Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive pregnancy test.
Female patients physiologically capable of becoming pregnant UNLESS they are patients whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, or whose partners have been sterilized by vasectomy or other means or using an acceptable method of contraception.
Familial and social conditions rendering regular medical assessment not possible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Target dose of canakinumab for the treatment of acute flares in gout patients who are refractory or contraindicated to NSAIDs and/or colchicine.
The target dose is the dose that leads to the same efficacy as the comparator and will be identified by assessing the dose response relationship of various doses of canakinumab with regards to the pain intensity in the target joint at 72 hours (Day 4) post-dose measured on a 0-100 mm Visual Analog Scale (VAS). |
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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 | No |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.1.7.1 | Other trial design description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial months | 7 |