E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10064900 |
E.1.2 | Term | Gout flare |
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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 determine the efficacy of 160 mg and 80 mg of subcutaneous (SC) rilonacept therapy compared to placebo in the prophylaxis of flares in subjects with intercritical gout initiating therapy with allopurinol. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of rilonacept on Quality of Life To assess the safety and tolerability of rilonacept
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female 18 - 80 years of age 2.Previously met the preliminary criteria of the American Rheumatism Association (ARA) for the classification of the acute arthritis of primary gout (if any 6 or more of the 13 criteria are present, serially or simultaneously, during any interval of observation) or monosodium urate monohydrate microcrystals have been identified in joint fluid 3.Serum uric acid ≥ 7.5 mg/dL at screening and, according to treating physician or investigator, the subject is a candidate for and does not have any contraindication to treatment with allopurinol 4.A self-reported history of ≥ 2 gout flares in the year prior to the Screening Visit 5.For men and women of childbearing potential, willingness to utilize adequate contraception and not become pregnant (or have their partner[s] become pregnant) during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to screening) and other prescription pharmaceutical contraceptives; IUD; bilateral tubal ligation; vasectomy; condom or diaphragm plus either contraceptive sponge, foam or jelly 6.Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures 7.Able to read, understand and willing to sign the informed consent form 8.Able to read, understand, and complete study-related questionnaires and diary
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E.4 | Principal exclusion criteria |
1.Subjects with acute gout flare in the 2 weeks prior to the Screening Visit or during Screening 2.Are pregnant, nursing, or planning a pregnancy or fathering a child within 3 months after receiving the last administration of study drug 3.Have a known or suspected current active infection or a history of chronic or recurrent infectious disease including but not limited to chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, an open, draining, infected skin wound 4.Within 2 months of first study drug administration, have had a serious infection, have been hospitalized for an infection, have been treated with PO antibiotics for greater than 2 weeks, or have been treated with IV antibiotics for an infection 5.Subjects with chronic active gouty arthritis 6.Evidence of prior or current infection in any affected joint 7.Subjects with a history of inadequate urate-lowering response to allopurinol or history of allergic reaction, contraindication, or intolerance to allopurinol 8.Uncontrolled diabetes, defined as HbA1c ≥ 9.0% at the Screening Visit 9.Subjects requiring dialysis 10.Subjects who have had an organ transplant 11.Treatment with any systemic immunosuppresants (e.g. methotrexate, azathioprine, cyclosporine, mercaptopurine, mycophenolate mofetil, tacrolimus, sirolimus, leflunomide, etanercept, adalimumab, infliximab, abatacept, natalizumab, rituximab) within 6 months prior to Baseline Visit; anakinra within 30 days of Baseline Visit 12.Treatment with pegloticase within 6 months of Baseline Visit 13.History of a demyelinating disease or symptoms suggestive of multiple sclerosis 14.Use of oral, intraarticular (IA), intramuscular (IM) or intravenous (IV) glucocorticoids in the 4 weeks prior to the Screening Visit 15.Use of colchicine within 1 month prior to the Screening Visit 16.Use of allopurinol, benzbromarone, febuxostat, probenecid or sulfinpyrazone within 3 months prior to the Screening Visit 17.Treatment with a live (attenuated) virus vaccine during the 3 months prior to Screening Visit 18.Estimated glomerular filtration rate (eGFR) < 30 mL/min 19.Screening Laboratory test results meeting any of the following criteria: •Hemoglobin (Hgb) < 8.5 g/dL; •White blood cell (WBC) count < 3.0 x 103/μL ; •Neutrophil count < 1.5 x 103/μL •Platelet count < 100 x 103/μL ; •Total bilirubin exceeding 1.5 times the upper limit of normal unless consistent with Gilbert's syndrome; •AST/ALT > 2.0 x ULN [Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding 2 times the upper limit of normal] 20.For sites in South Africa: HIV antibody positive For sites in all other countries: History of HIV by clinical or serological history 21.Hepatitis B surface antigen (HBsAg) and/or Hepatitis C antibody (HCV) by serologic testing 22.Chest radiograph (or historic results within 3 months of Screening Visit) that shows evidence of malignancy or any abnormalities suggestive of prior tuberculosis infection, including, but not limited to, apical scarring, apical fibrosis, or multiple calcified granulomata. This does not include non-caseating granulomata 23.TB criteria: •History of active TB prior to screening •Signs or symptoms suggestive of active TB (e.g. new cough of > 14 days in duration or a change in chronic cough, persistent fever, unintentional weight loss, night sweats) upon review of medical history and/or physical examination •Have recent close contact with a person with active TB •History of latent untreated TB 24.For sites in South Africa, Indonesia, India, and Taiwan: A positive intradermal tuberculin skin test (PPD 5 TU) ≥ 10 mm induration read at 48 to 72 hours by a qualified health professional For sites in all other countries: A positive intradermal skin tuberculin test (PPD 5 TU) ≥ 5 mm induration read at 48 to 72 hours by a qualified health professional 25.Any other arthritic or medical condition that in the opinion of the investigator could adversely affect the subject’s participation or interfere with evaluations. This includes significant concomitant illness such as, but not limited to, cardiac, renal, neurological, endocrinological, metabolic, pulmonary, gastrointestinal, or psychiatric disease 26.Not listed due to character limitation, please refer to protocol. 27.History of a myeloproliferative disorder 28.Not listed due to character limitation, please refer to protocol.29.History of drug abuse within the 5 years prior to the Screening Visit 30.Use of NSAIDs within the two weeks prior to the Screening Visit 31.Subjects with previous exposure to rilonacept 32.Not listed due to character limitation, please refer to protocol. 33.Not listed due to character limitation, please refer to protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of gout flares per subject assessed from Day 1 to Week 16. For analysis, a gout flare will be defined as subject-reported acute articular pain typical of a gout attack that is deemed (by subject and/or investigator) to require treatment with an anti-inflammatory therapeutic; presence of at least three of the following four signs/symptoms: joint swelling, redness, tenderness and pain, and at least one of the following: rapid onset of pain, decreased range of motion, joint warmth or other symptoms similar to a prior gout flare. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 14 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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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Last visit of the last subject |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |