Rilonacept for Treatment of Familial Mediterranean Fever (FMF)
Condition: Familial Mediterranean Fever
MeSH terms: Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Fever; Hyperthermia
Intervention: Rilonacept; Placebo
Intervention description: 2.2 mg/kg/wk by subcutaneous injection, for 3 months; placebo by subcutaneous injection weekly for 3 months
Intervention MeSH terms: Rilonacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 14.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: FMF; IL1 Trap (Rilonacept); Periodic fever syndromes; Autoinflammatory syndromes; Familial Mediterranean Fever; colchicine

Summary:

      Familial Mediterranean fever (FMF) is a genetic disease resulting in recurrent attacks of
      fever, abdominal pain, chest pain, arthritis and rash. There are 5-15% of patients who
      continue to have FMF attacks despite treatment with colchicine or who cannot tolerate
      colchicine. Currently there are no alternatives to colchicine. Pyrin, the protein that has a
      defect in FMF has an important role in the regulation of a molecule called interleukin (IL)-1
      beta production and activity. This molecule is very important in the process of inflammation
      in FMF.

      Therefore we propose to use IL-1 Trap (Rilonacept), a medication that binds and neutralizes
      IL-1.

      We will enroll in this study 17 subjects from the age of 4 years, including adults with
      active FMF despite colchicine therapy. Subjects will receive in random order two 3-month
      courses of Rilonacept at 2.2 mg/kg (maximum 160 mg) by weekly subcutaneous injection and two
      3-month courses of placebo injection. If patients have at least two FMF attacks during a
      treatment course they will be able to get if they choose the other treatment until the end of
      that treatment course. Our hypothesis is that Rilonacept will decrease the number of acute
      FMF attacks and will be safe to use. This study may confirm the importance of IL-1 in the
      cause of FMF.

      Funding source - FDA Office of Orphan Products Development
    

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.