Rilonacept for Treatment of Familial Mediterranean Fever (FMF)
Familial Mediterranean Fever
About this trial
This is an interventional treatment trial for Familial Mediterranean Fever focused on measuring FMF, IL1 Trap (Rilonacept), Periodic fever syndromes, Autoinflammatory syndromes, Familial Mediterranean Fever, colchicine
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital Los Angeles/Cedars-Sinai Medical Center
- Children's Hospital of Central California
- NIH
- NYU Hospital for Joint Diseases
- Cleveland Clinic
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
1
2
Treatment Arm A: Rilonacept (IL-1 Trap) at a dose of 2.2 mg/kg/wk (max 160 mg)given by subcutaneous injection for 3 months plus colchicine at a stable dose for those subjects already taking colchicine, or without colchicine for those intolerant or non-compliant with colchicine. Since the colchicine dose is stable throughout the study for each subject, at the prestudy dose, colchicine was not considered an intervention
Treatment Arm B: Placebo given by subcutaneous injection weekly with or without colchicine for 3 months. Since the colchicine dose is stable throughout the study for each subject, at the prestudy dose, colchicine was not considered an intervention.