Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-label, Exploratory Study to Establish the Safety and Efficacy of 3 Months Treatment With Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever
Brief Summary: Establish the safety and efficacy of 3 months treatment with canakinumab in patients with colchicine resistant Familial Mediterranean Fever.


Options:
A: Inclusion Criteria:

* Subject has a definitive diagnosis of FMF as by the Tel-Hashomer clinical criteria (long version of criteria) with at least one mutation on one of the MEFV gene alleles. However, subjects with an isolated heterozygous mutation of exon 2 of the MEFV gene (including E148Q) will not be eligible.
* Subject must have an estimated mean of at least one acute FMF attack per month before and during the month of screening.
* Subject is at least four years of age (with no upper limit of age).
* Subjects must have received an adequate trial of colchicine defined as treatment of at least 1.5 mg/d for at least 3 months if ≥6 years old or 1.2 mg/d if less than 6 years, or an inability to tolerate colchicine due to adverse effects in a dose that controls acute attacks in the frequency of less than one attack per month.
* If subject is being treated with anakinra at the time of consent, washout must be done (about 3 days). Subject must experience 2 attacks before randomization visit can occur.
* If subject has been treated previously with anti-TNF drugs, appropriate washout must be done. Etanercept must be discontinued for 4 weeks prior to randomization; Adalimumab and Infliximab must be discontinued for 8 weeks prior to randomization.
* If subject is a female of childbearing potential, she must agree to use adequate contraception (adequate contraception can include abstinence) for the duration of the trial and 3 months after and must have a negative serum or urine pregnancy test prior to administration of study medication.
* If subject is a male and has reached puberty, he must agree to use adequate contraception or abstinence during the study and for 3 months after discontinuation from study.
* Subject's parent or legal guardian has provided written informed consent prior to screening for this study or if subject is older than 18 years has provided informed consent him/herself.
* Subject, if applicable, has assented to participate prior to screening for this study.
* Subject and, if applicable, parent/legal guardian, agree to comply with study requirements and are able to come to the clinic for all required study visits.

Exclusion Criteria:

* The subject has existing biopsy proven amyloidosis or proteinuria \>0.5 gram per day.
* The subject has another active inflammatory rheumatic disease.
* The subject has an active malignancy of any type, or history of a malignancy.
* The subject has active GI disease (e.g., inflammatory bowel disease), a chronic or acute renal or hepatic disorder, or a significant coagulation defect.
* The subject has an AST (SGOT), ALT (SGPT) or BUN \>2 x ULN or creatinine \>1.5 mg/dL or any other laboratory abnormality considered by the examining physician to be clinically significant within 28 days before the Baseline visit.
* Current use of an anti-tumor necrosis factor drug.
* The subject has, in the investigator's opinion, a chronic condition (e.g., diabetes, epilepsy) that is either not stable or well-controlled and may interfere with the conduct of the study.
* The subject has received any investigational medication within 30 days before the first dose of study medication or is scheduled to receive an investigational drug, other than study medications described in this protocol, during the course of the study.
* The subject has chronic or active infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to the screening evaluation.
* The subject has known positive human immunodeficiency virus (HIV) status.
* The subject has known past or current hepatitis.
* The subject has received a live virus vaccine within 1 month prior to the baseline visit.
* The subject has a positive PPD test.
* The subject is sexually active and not practicing effective birth control.
* The subject is pregnant or breast feeding a child.
* Any concurrent medical condition which would, in the investigator's opinion, compromise the subject's ability to tolerate the study drug or would make the subject unable to cooperate with the protocol.
* History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
* Subject has a history of alcohol or drug abuse within the past 6 months that would interfere with ability to comply with protocol requirements.
* Inability to comply with the study requirements for any reason.
B: Inclusion Criteria:

A subject must fulfil the following criteria in order to be included in the study:

1. FMF diagnosed as per the Tel-Hashomer criteria -(Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum.1998 Aug; 41(8):1516-7-Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M).
2. 18-65 years of age
3. Verified as mutations in both alleles of the MEFV gene, thus including homozygous and compound heterozygous patients
4. Patient compliant with maximum tolerable dose of colchicine (up to 3 mg/day)
5. At least one FMF attack per month in chest, abdomen or joints (definition of attack see above)
6. Adequate contraception for sexually active male and female patients

Exclusion Criteria:

The presence of any of the following will exclude a subject from inclusion in the study:

1. Patient pregnant at enrolment visit
2. Prior or existing malignancy
3. Active infection
4. Manifest renal failure with Creatinine clearance \<30mL/min as determined by the equation Creatinine clearance (ml/min) = (140-age) x Wight (Kg) /72 x serum creatinine (mg/dcl) For women one should multiply the results by 0.8
5. Live vaccinations last three months before enrolment
6. Sociopsychological state threatening compliance with the treatment protocol
7. Alcohol or substance abuse
8. Concomitant medication with biological or anti-rheumatic disease-modifying drugs or systemic steroids
9. Any prior use of IL-1 inhibitory drugs
10. Associated disease that could interfere with clinical assessment:

    1. Rheumatic disorder
    2. Systemic disease, e.g. autoimmune or other autoinflammatory disorder, diabetes, hypertension, vasculitis, Behçet's disease
    3. Gastrointestinal disorder, e.g. Crohn's disease, ulcerative colitis, irritable bowel syndrome
    4. Cardiovascular disorder, e.g. post myocardial infarction, angina
    5. Pulmonary disorder, e.g. COPD, pulmonary hypertension
    6. Any other condition which in the opinion of the investigator makes the subject unsuitable for inclusion
11. Enrolment in another concurrent clinical study, or intake of an investigational drug, within three months prior to inclusion in this study
12. Failure or refusal to cooperate with given instructions

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C: Inclusion Criteria:

* Male and female patients between 12 and 75 years of age with active type 1 FMF disease (according to Tel-Hashomer criteria for diagnosis of FMF) despite colchicine therapy (1.5 to 2.0 mg/day).
* Patients who are intolerant to effective doses of colchicine (1.5 to 2 mg/day)
* Patients with demonstrated minimum 1 typical acute attack per month and genetic confirmation of diagnosis (with at least one of the known MEFV gene exon 10 mutations). Patients with manifested amyloidosis are excluded.
* Patients must have a historical data showing a frequency of at least 1 attack/month within the last 3 months before they can be enter the run-in period.
* Patients must have type 1 disease characterized by recurrent and short episodes of inflammation and serositis with an average of at least 1 documented acute FMF attack per month during the previous 6 months and lasting approximately 12 to 72 hours.
* Patients treated with IL-1 therapies must complete washout and have experienced at least 2 attacks since (e.g. Anakinra: 3 day washout; Rilonacept: 3 week washout)
* Patients treated with anti-TNF drugs must undergo appropriate washout. Prior to randomization, use of Etanercept must be discontinued for 4 weeks or use of Adalimumab or Infliximab must be discontinued for 8 weeks.
* Female subjects of childbearing potential must be using two acceptable methods of contraception
* Patients treated with Interferon therapies must complete 1 month washout period.

Exclusion Criteria:

* Patients with end-organ dysfunction due to amyloidosis (e.g. existing biopsy proven amyloidosis or proteinuria \> 0.5 gram per day)
* Patients taking steroids within 1 month prior to baseline
* Presence or history of any other inflammatory rheumatic disease
* Positive PPD test (according to local guidance) where a latent or active TB infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed).
* Patients who are pregnant or lactating
* Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
* History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin

Other protocol-defined inclusion/exclusion criteria may apply
D: Inclusion Criteria:

1. Male or female 18 - 70 years of age
2. Previously met the preliminary criteria of ARA for the classification of the acute arthritis of primary gout
3. Presenting with an acute attack (flare) of gout within 48 hours of pain onset and pain of at least moderate severity
4. Must have at least 1 on the 0-3 scale for the swelling and the tenderness assessments of the gouty index joint
5. Current presentation of acute gout flare in 3 joints or less

Exclusion Criteria:

1. Treatment with any non-steroidal anti-inflammatory drug (NSAIDs) or opiates within 48 hours prior to baseline assessments. Treatment with long-acting NSAIDs within 1 month prior to baseline visit. Treatment with naproxen, meloxicam, nabumetone, celecoxib and indomethacin SR within 5 days prior to baseline visit.
2. Treatment with oral analgesics within 6 hours before baseline assessments. Treatment with topical analgesics within 12 hours before baseline assessments
3. History of NSAID intolerance
4. Participants with history of chronic, gouty arthritis

Answer: C