Rilonacept for Deficiency of the Interleukin-1 Receptor Antagonist (DIRA)
Condition: DIRA
Intervention: Rilonacept
Intervention MeSH terms: Rilonacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 3 Months
Healthy volunteers: No
Keywords: DIRA; Clinical Trial; IL-1; Autoinflammatory Syndrome; Rilonacept

Summary:

      Background:

      - Deficiency of the IL-1 receptor antagonist (DIRA) is a condition that causes repeated
      episodes of inflammation. People with DIRA can have rashes, fever, and joint pain. Most
      treatments for DIRA are intended to control the immune system to stop these inflammations.
      There are drugs that can treat DIRA, but they have to be given daily as injections.
      Researchers want to try another drug, rilonacept, as a treatment for DIRA. It needs to be
      given only once a week. Rilonacept will be given to individuals who are at least 3 months old
      and who have DIRA.

      Objectives:

      - To test the safety and effectiveness of rilonacept for children and adults with DIRA.

      Eligibility:

      - Individuals at least 3 months old who have DIRA.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Other tests to study pain and movement will be given. Imaging
           studies such as bone density scans and x-rays may also be taken.

        -  Participants will have a minimum of four to five study visits over 12 months. Those who
           are on different anti-inflammatory drugs (such as anakinra) will stop taking them before
           beginning the study visits.

        -  Participants will have rilonacept injections weekly while on this study. The dose will
           be adjusted as needed to help treat the DIRA symptoms. Participants will keep a diary to
           monitor their symptoms and any side effects.

        -  Treatment with rilonacept will be given for 1 year. Participants will have study visits
           to monitor the treatment. They will provide blood samples and have other tests at these
           study visits.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

               1. Male or female pediatric and adult subjects with mutation positive IL1RN
                  indicating DIRA. For the first five patients enrolled, they must have been on a
                  stable dose of anakinra during the 2-week period prior to screening visit. If the
                  subject is on other medications such as NSAIDs, methotrexate and/or oral
                  steroids, it is a requirement that these doses have been stable during the 2-week
                  period prior to screening visit.

               2. Subjects greater or equal to 3 months of age (however the first 5 patients
                  enrolled will be over 2 years of age). Subjects 3 months old or older will be
                  enrolled after SMC data review of the first 5 enrolled patients.

               3. Participation in NIH study #03-AR-0173 ( Studies of the Natural History,
                  Pathogenesis and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CRMO,
                  Still s Disease, Behcet s Disease, and other Undifferentiated Autoinflammatory
                  Diseases )

               4. Subjects currently treated with anakinra may be enrolled in this study even
                  though their DIRA may be quiescent. For these subjects, a history of active DIRA
                  prior to treatment with anakinra will be sufficient. Subjects will not take
                  anakinra 24 hours before initiation of drug treatment. Treatment naive patients
                  will also be enrolled after SMC data review of the first 5 enrolled patients.

               5. Females of childbearing potential (young women who have had at least one
                  menstrual period regardless of age) must have a negative serum pregnancy test at
                  screening and a urine pregnancy test prior to administration of study medication.

               6. Females of childbearing age and men able to father a child and who are sexually
                  active, who agree to use two forms of effective birth control, including
                  abstinence.

               7. Negative Purified Protein Derivative (PPD) test using 5 T.U. intradermal testing
                  or the QuantiFERON(SqrRoot) - TB Gold test per the Centers for Disease Control
                  and Prevention (CDC) guidelines, and no evidence of active tuberculosis (TB) on
                  chest X-ray.

                  Subjects with latent TB (positive PPD or QuantiFERON - TB Gold test) currently
                  treated with adequate therapy for at least one month prior to first dose of study
                  medication may be included. Full prophylaxis regimens will be continued while on
                  the study.

                  Subjects who have had active TB in the past with documentation of adequate
                  treatment may be included with strict clinical and radiological follow-up as per
                  current guidelines.

                  The Infectious diseases service will be consulted regarding all patients with
                  evidence of TB infection (latent or active, current or history) prior to
                  enrollment, and as appropriate during the study.

                  Subjects who have been BCG-vaccinated will also be tested. Interpretation of PPD
                  and QuantiFERON - TB Gold test in BCG recipients will be the same as for subjects
                  who have not received BCG vaccine.

                  Guardian/parent able to understand, and complete study-related questionnaires.

                  Guardian/parent able and willing to give informed consent and abide with the
                  study procedures.

                  EXCLUSION CRITERIA

               1. Treatment receiving a live virus vaccine (such as the measles, mumps, and rubella
                  vaccine) during the 3 months prior to baseline visit. No live vaccines will be
                  allowed throughout the course of this study.

               2. Presence of active infections or a history of pulmonary TB infection without
                  documented adequate therapy. Subjects with current active TB, or recent close
                  exposure to an individual with active TB, are excluded from the study. Exceptions
                  include patients with latent TB treated with adequate therapy for at least one
                  month prior to the first dose of study medication, and patients with history of
                  TB with documentation of adequate treatment.

               3. Positive test for, or prior history of, HIV, or Hepatitis B or C.

               4. History of malignancy. Subjects deemed cured of superficial malignancies such as
                  cutaneous basal or squamous cell carcinomas, or in situ cervical cancer may be
                  enrolled.

               5. Known hypersensitivity to Chinese Hamster Ovary cell-derived biological or any
                  components of rilonacept.

               6. Presence of any additional rheumatic disease or significant systemic disease. For
                  example, major chronic infectious/ inflammatory/ immunologic disease (such as
                  inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, SLE in
                  addition to autoinflammatory disease).

               7. Presence of any of the following laboratory abnormalities at enrollment visit:

                  creatinine greater than 1.5xULN

                  WBC less than 3.0x103/mm3

                  ANC less than 800 cells/mL

                  platelet count less than 150,000 mm3

                  ALT or AST greater than 2.0x ULN.

               8. Lactating, breastfeeding or pregnant females.

               9. Enrollment in any other investigational treatment study or use of an
                  investigational agent, or has not yet completed at least 4 weeks or 5 half-lives,
                  whichever is longer, since ending another investigational device or drug trial.

              10. Subjects for whom there is concern about compliance with the protocol procedures.

              11. Presence of other severe acute or chronic medical or psychiatric condition, or
                  significant laboratory abnormality requiring further investigation that may cause
                  undue risk for the subject s safety, inhibit protocol participation, or interfere
                  with interpretation of study results, and in the judgment of the Investigator
                  would make the subject inappropriate for entry into this study.

              12. Subjects who have received a DMARDs (except methotrexate) and or TNFblocking
                  agent within 4 half-lives prior to study entry.

              13. Men able to father a child and who are sexually active, who do not agree to use 2
                  form of effective birth control, including abstinence during the duration of the
                  study an for at least 28 days following the last dose of rilonacept.

              14. Females of childbearing potential (woman greater than 12 or who have had at least
                  1 menstrual period regardless of age) who are sexually active and who do not
                  agree to use 2 effective methods of birth control, including abstinence during
                  the duration of the study an for at least 28 days following the last dose of
                  rilonacept.