Anakinra to Treat Patients With Neonatal Onset Multisystem Inflammatory Disease
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ClinicalTrials.gov Identifier: NCT00069329 |
Recruitment Status
:
Terminated
(data submitted for Food and Drug Administration (FDA) approval)
First Posted
: September 23, 2003
Results First Posted
: December 1, 2016
Last Update Posted
: December 1, 2016
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Nervous System Malformations Arthropathy, Neurogenic Urticaria Papilledema | Drug: anakinra | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 43 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Long-Term Outcome Study With the IL-1 Receptor Antagonist Anakinra/Kineret in Patients With Neonatal Onset Multisystem Inflammatory Disease (NOMID/CINCA Syndrome) A Therapeutic Approach to Study the Pathogenesis of This Disease |
Study Start Date : | September 2003 |
Actual Primary Completion Date : | April 2010 |
Actual Study Completion Date : | April 2010 |

Arm | Intervention/treatment |
---|---|
Experimental: NOMID treatment arm
All patients enrolled received daily doses of subcutaneous injection of increased doses of anakinra starting at 0.5mg/kg/day up to a maximum 10mg/kg/day to achieve disease remission.
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Drug: anakinra
daily injection of subcutaneous injection
Other Name: Kineret
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- Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches) [ Time Frame: Baseline ]"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
- Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches) [ Time Frame: 36 months ]"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
- Diary Symptom Sum Score (DSSS) (Fever, Rash, Joint Pain, Vomiting, and Headaches) [ Time Frame: 60 months ]"The severity of the main symptoms of the disease were scored on a scale from 0 (no symptoms) to 4 (highest severity) on a daily basis using a diary. Five key symptoms were included in the primary variable DSSS: fever, headache, rash, joint pain, and vomiting. Each of the diary variables was evaluated as a mean value for a period preceding the visits. The baseline value was the mean value of the 5-30 last days before the first dose of Kineret. For the subsequent visits, the mean value of the last 30 days with data before each visit was used as the response variable."
- Patient / Parent Global Score of Overall Disease Activity [ Time Frame: Baseline ]Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
- Patient / Parent Global Score of Overall Disease Activity [ Time Frame: 36 months ]Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
- Patient / Parent Global Score of Overall Disease Activity [ Time Frame: 60 months ]Visual analog assessment of how arthritis affects the patient as rated by the patient themselves or parent. Measured on scale from very well (0 mm) to very poor (100 mm).
- Parent /Patient Pain Rating [ Time Frame: Baseline ]Visual analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
- Parent /Patient Pain Rating [ Time Frame: 36 months ]Visual analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
- Parent /Patient Pain Rating [ Time Frame: 60 months ]Visual Analog assessment of how much pain the patient experienced in past week due to illness as rated by the patient themselves or parent. Measured on scale from no pain (0 mm) to very severe pain (100 mm).
- Childhood Health Assessment Questionnaire (CHAQ) [ Time Frame: Baseline ]Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
- Childhood Health Assessment Questionnaire (CHAQ) [ Time Frame: 36 months ]Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities.Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
- Childhood Health Assessment Questionnaire (CHAQ) [ Time Frame: 60 months ]Patient self-assessment (or parent assessment) for how illness affects ability to function in daily life. Includes overall score, overall pain rating, overall global evaluation, subcategories for dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Measured on scale of 0-3 from 'Without any difficulty' (0) to 'Unable to do' (3).
- Serum Amyloid A (SAA) Measurement [ Time Frame: Baseline ]Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
- Serum Amyloid A (SAA) Measurement [ Time Frame: 36 months ]Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
- Serum Amyloid A (SAA) Measurement [ Time Frame: 60 months ]Serum Amyloid A is an inflammatory marker for NOMID measured using Rapid Automated Enzyme Immunoassay. Normal SAA values were defined as ≤ 10 mg/liter.
- C-reactive Protein (CRP) Measurement [ Time Frame: Baseline ]C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
- C-reactive Protein (CRP) Measurement [ Time Frame: 36 months ]C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
- C-reactive Protein (CRP) Measurement [ Time Frame: 60 months ]C-reactive protein (CRP) is an inflammatory marker for NOMID. Systemic inflammatory remission was defined as a normal CRP level (≤0.5mg/dl). Analyzed at the NIH Clinical Center Laboratory.
- Erythrocyte Sedimentation Rate (ESR) Measurement [ Time Frame: Baseline ]Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.
- Erythrocyte Sedimentation Rate (ESR) Measurement [ Time Frame: 36 months ]Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.
- Erythrocyte Sedimentation Rate (ESR) Measurement [ Time Frame: 60 months ]Erythrocyte Sedimentation Rate (ESR) is an inflammatory marker for NOMID. Normal ESR values are defined as ≤ 25 mm/hour. Analyzed at the NIH Clinical Center Laboratory.

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Ages Eligible for Study: | Child, Adult, Senior |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
-INCLUSION CRITERIA:
- There is no age limitation.
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Patients fulfill at least 2 of the following 3 clinical manifestations:
- Typical NOMID rash
- CNS involvement (papilledema, CSF pleocytosis, sensorineural hearing loss)
- Typical arthropathic changes on radiograph (epiphyseal and/or patellar overgrowth.
- Onset of manifestations of NOMID/CINCA at less than or equal to 6 months of age.
- Stable dose of steroids, NSAIDs, DMARDs for 4 weeks prior to enrollment visit.
- Washout period for biologics: 6 half-lives before anakinra administration for all drugs with anti TNF properties. For etanercept (6 half-lives=24 days) this calculates to drug discontinuation 3 days before enrollment into the observation period, for infliximab and adalimumab (6 half-lives=48 days) drug will be discontinued 27 before the observation period, and for thalidomide (6 half-lives=3 days) drug will be discontinued for 3 days prior to anakinra administration.
- Patient's or legal guardian's ability and willingness to give informed consent.
- Females of childbearing potential (young women who have had at least one menstrual period regardless of age) must have a negative urine pregnancy test at baseline prior to performance of any radiologic procedure or administration of study medication. Women of childbearing age and men able to father a child, who are sexually active, will be asked to use a form of effective birth control, including abstinence.
- Negative PPD test using 5 T.U. intradermal testing per CDC guidelines with exception of inclusion criteria #9 below.
- Patients with latent TB (positive PPD test) must have adequate therapy for TB initiated prior to first dose of study medication as recommended in published guidelines.
EXCLUSION CRITERIA:
- Having received live virus vaccine during 3 months prior to baseline visit (1st visit to NIH).
- Patients with active infections or a history of pulmonary TB infection with or without documented adequate therapy, Patients with current active TB, or recent close exposure to an individual with active TB are excluded from the study.
- Positive testing for HIV, Hepatitis B or C known or documented at screening, enrollment or baseline visit.
- Have a history of or concomitant diagnosis of congestive heart failure.
- History of malignancy.
- Recent use of IL-1 antagonist within the last three months or prior use of anti CD4 antibody.
- Known hypersensitivity to E. coli derived products or any components of anakinra.
- Presence of any other rheumatic disease or major chronic infectious/inflammatory/immunologic disease (e.g. inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, SLE in addition to NOMID/CINCA).
- Presence of the following at enrollment visit: ALT or AST greater than 2.0 x upper limit of normal (ULN) of the local laboratories values, creatinine greater than 1.5 xULN, WBC less than 3.6x10(9)/l; platelet count less than 150,000 mm(3).
- Enrollment in any other investigational clinical study or receiving an investigational agent, or has not yet completed at least 4 weeks since ending another investigational device or drug trial.
- Subjects for whom there is concern about compliance with the protocol procedures by subject and/or parent/s and legally acceptable representative/s.
- Lactating females or pregnant females.
- Patients with asthma will only be included after evaluation by a pulmonary and infectious disease consultation.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00069329
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | |
Bethesda, Maryland, United States, 20892 |
Principal Investigator: | Raphaela T Goldbach-Mansky, M.D. | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
ClinicalTrials.gov Identifier: | NCT00069329 History of Changes |
Other Study ID Numbers: |
030298 ZIAAR041138-08 ( U.S. NIH Grant/Contract ) 03-AR-0298 ( Other Identifier: NIHCC ) |
First Posted: | September 23, 2003 Key Record Dates |
Results First Posted: | December 1, 2016 |
Last Update Posted: | December 1, 2016 |
Last Verified: | October 2016 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | with Swedish Orphan Biovitrum Inc (SOBI) |
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ):
Central Nervous System Abnormalities Arthropathy Urticaria Papilledema |
Auto-Inflammation Inflammatory Disease Neonatal Onset Multisystem Inflammatory Disease NOMID CINCA Syndrome |
Additional relevant MeSH terms:
Congenital Abnormalities Urticaria Joint Diseases Cryopyrin-Associated Periodic Syndromes Papilledema Arthropathy, Neurogenic Nervous System Malformations Skin Diseases, Vascular Skin Diseases Hypersensitivity, Immediate Hypersensitivity |
Immune System Diseases Musculoskeletal Diseases Hereditary Autoinflammatory Diseases Genetic Diseases, Inborn Skin Diseases, Genetic Optic Nerve Diseases Cranial Nerve Diseases Nervous System Diseases Eye Diseases Interleukin 1 Receptor Antagonist Protein Antirheumatic Agents |