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Sponsored by: |
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00069329 |
This study will evaluate the safety and effectiveness of anakinra (Kineret® (Registered Trademark)) for treating patients with neonatal onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurological, cutaneous and arthropathy (CINCA) syndrome. This disease can cause rash, joint deformities, brain inflammation, eye problems, and learning difficulties. Immune suppressing medicines commonly used to treat NOMID do not completely get rid of the disease symptoms and, if used for a long time in high doses, can cause harmful side effects. Anakinra, approved by The Food and Drug Administration for treating rheumatoid arthritis in adults, blocks a substance called IL-1 that may be an important factor in causing the inflammation in NOMID.
Patients 2 years of age and older with NOMID whose disease symptoms appeared by at least 6 months of age may be eligible for this study.
During a 3-week observation before beginning medication, patients will have a physical examination and evaluation of their condition. They will keep a daily diary of symptoms ratings, and will have blood drawn once a week to measure inflammation and monitor disease. At the end of this period, patients will be admitted to the NIH Clinical Center for 5 days to start daily anakinra injections, given under the skin of the thigh, upper arm, or belly. They will also be taught how to self-inject the medication. After 3 months on medication, patients will be randomly assigned to: 1) continue taking anakinra, or 2) receive a placebo injection (an inactive substance identical in appearance to the study drug). Follow-up visits at NIH for 5 days each will be scheduled at 1, 3, and 12 months, plus one visit between months 5 and 7. During this time, patients will undergo the following procedures:
Between NIH visits, patients will be evaluated by their local doctor once a month for a checkup, blood tests, symptoms review, evaluation of drug side effects, and completion of quality of life questionnaires.
Condition | Intervention | Phase |
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Nervous System Malformations Arthropathy, Neurogenic Urticaria Papilledema |
Drug: Anakinra |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A Pilot Study With the IL-1 Receptor Antagonist Anakinra or Kineret in Patients With Neonatal Onset Multisystem Inflammatory Disease (NOMID/CINCA Syndrome) |
Estimated Enrollment: | 21 |
Study Start Date: | September 2003 |
This is a multi-center pilot study using the IL-1 receptor antagonist anakinra to treat children with Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as chronic infantile neurological, cutaneous and arthropathy (CINCA) syndrome. NOMID/CINCA syndrome is a rare genetic systemic auto-inflammatory disease that is characterized by a triad of symptoms, including a persistent urticaria-like skin rash, an arthropathy associated with patellar and epiphyseal osseous overgrowth, and neurological manifestations, including chronic aseptic meningitis, optic disc edema, high frequency hearing loss, and mental retardation. Spontaneous genetic mutations in the NACHT domain of CIAS1, a gene located on chromosome 1, have been recently identified in about half of the patients with NOMID/CINCA syndrome. CIAS1 encodes a protein, cryopyrin that is associated with up-regulation of IL-1 production in vitro, which has formed the rationale to target the IL-1 pathway in children with NOMID. We plan to enroll a total number of 20 patients into this study. During a 3-week enrollment period before initiating therapy, we will collect self/parent reported daily diary data and serological samples on 3 occasions one week apart, to determine baseline disease activity. These data may be gathered by collaborating centers. At the end of the observation period, patients will be admitted to the NIH for a standardized clinical evaluation and initiation of treatment with anakinra administered at 1mg/kg/day by regular daily subcutaneous injections (study phase 1). Patients will be re-evaluated after one month and every month thereafter. If patients do not fulfill improvement criteria at 1 month, the dose will be escalated at 2.0 mg/kg/day with a maximum dose of 200 mg/day, while patients fulfilling response criteria will maintained on a 1mg/kg/dose (study phase 2). At three to four months, patients enter phase 3 of the study. Patients with stable disease and significant improvement will have drug withheld for 7 days during an observed hospital visit. Inflammatory parameters such as ESR, CRP and serum amyloid A (SAA) levels at the end of this phase will be compared to levels on treatment prior to withdrawal. The clinical improvement at 3-4 months and the change in serum amyloid A levels (a sensitive inflammatory marker) from before treatment to 3-4 months post treatment, change in SAA levels after 7 days of drug withdrawal, and drug safety are the primary clinical outcomes of this study. The withdrawal phase of the study was discontinued after 11 patients were withdrawn. After one week of drug withdrawal, anakinra will be re-started at the same dose as before drug was withdrawn. To assess long-term safety and efficacy, all patients will be observed during this open label extension phase of the study (phase 4) until they have received 12 months of anakinra. Clinical and laboratory parameters will be used to assess safety and efficacy throughout the trial. All patients will be seen every 6 months and annually (as calculated from initiation of anakinra treatment) to further evaluate safety and long term outcomes (phase 5). During the open ended extension phase of the study (phase 5), patients who have residual clinical or laboratory evidence of active inflammation despite taking 3 mg/kg/day of anakinra may have their dose increased in 0.5 mg/kg/day increments up to a maximum dose of 5 mg/kg/day, if clinically necessary. In addition, since no data on the pharmacokinetics of anakinra in pediatric patients is available with doses exceeding 2 mg/kg/day, we plan to determine the pharmacokinetics of anakinra with each dose escalation.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
-INCLUSION CRITERIA:
Patients fulfill at least 2 of the following 3 clinical manifestations:
EXCLUSION CRITERIA:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | ( NIAMS ) |
Study ID Numbers: | 030298, 03-AR-0298 |
Study First Received: | September 22, 2003 |
Last Updated: | December 16, 2008 |
ClinicalTrials.gov Identifier: | NCT00069329 |
Health Authority: | United States: Federal Government |
Central Nervous System Abnormalities Arthropathy Urticaria Papilledema |
Auto-Inflammation Inflammatory Disease Neonatal Onset Multisystem Inflammatory Disease NOMID CINCA Syndrome |
Papilledema Skin Diseases Nervous System Malformations Joint Diseases Eye Diseases Urticaria Optic nerve disorder Arthropathy, Neurogenic |
Inflammation Hypersensitivity Musculoskeletal Diseases Hypersensitivity, Immediate Optic Nerve Diseases Interleukin 1 Receptor Antagonist Protein Congenital Abnormalities Chronic, Infantile, Neurological, Cutaneous, Articular syndrome |
Skin Diseases, Vascular Immune System Diseases Therapeutic Uses Nervous System Diseases |
Cranial Nerve Diseases Antirheumatic Agents Pharmacologic Actions |