Clinical trial NCT00770601
Conditions: NOMID CINCA Syndrome
Keywords: NOMID CINCA Syndrome Canakinumab
Sponsor: Novartis Pharmaceuticals
Start date: 2009-01-26; Completion date: 2011-02-17
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will examine whether a medicine called canakinumab is safe and effective for treating patients with neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. This disease can cause rash, joint deformities, brain inflammation, problems with the eyes and learning difficulties. Canakinumab is an experimental drug that inhibits the action of a protein produced by the body called human IL-1beta, which is responsible for the symptoms in NOMID and also contributes to many other kinds of inflammatory diseases.

Patients 2 years of age and older with NOMID / CINCA may be eligible for this study. Participants undergo the following procedures:

Screening Phase

* Medical history and review of medical records
* Blood tests
* Daily diary of symptoms and medicines take

Washout/Lead-in Phase

* Discontinuation of anakinra or other medications, a 6 to 48-hour run-in period (only for patients who discontinued anakinra or other IL-1 blocking therapy).

Treatment Phase

* Injection of canakinumab under the skin every 8 weeks for 6 months
* Monitoring and evaluations during treatment, including:
* Quality-of-life questionnaires and daily diary
* Vital signs measurements (heartbeat, blood pressure, temperature)
* Blood tests
* Electrocardiogram
* Tuberculosis skin test
* Neurological, eye and skin examinations at beginning and end of study
* Cognitive evaluation at beginning and end of study
* Lumbar puncture (spinal tap) at the beginning of the study, 2 weeks after the second dosing of canakinumab and at the end of the study
* X-rays and bone density scan at beginning and end of study
* Magnetic resonance imaging (MRI) of the head at beginning and end of study

Follow-up Phase

* Monthly clinic visits after the last dose of canakinumab for a minimum of 60 days

End-of-Study Evaluation

* Series of tests 8 weeks after last dose of canakinumab to evaluate treatment response and side effects

Detailed description:
This open-label study was designed to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of canakinumab, a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody, in patients with NOMID / CINCA syndrome. A total of 25 to 30 patients will be enrolled into the study. The study consists of two stages:

In the first pilot stage it is planned to enroll 5 patients undergoing PK/PD assessments in blood and cerebrospinal fluid (CSF), and monitoring of efficacy (CNS relapse and inflammatory relapse) to confirm the dose and dosing regimen before enlarging the number of patients enrolled into the study. Up to 5 additional patients may be enrolled in this stage if the variability of the responses to treatment is high. Interim analyses will be conducted as required. Following Stage 1, a second confirmatory stage will be conducted, enrolling 20 additional patients. In this stage patients will be treated with the dose and dosing regimen based on the assessment of the efficacy profile in Stage 1 and exploratory PK/PD assessment. In each stage there will be a 3-week screening period to collect pre-treatment parameters, a run-in period (only for patients who discontinue anakinra), a baseline evaluation prior to each drug administration, a 24-week treatment period with fixed dosing of canakinumab, and a study completion visit. Patients whose body weight is greater than 40 kg will receive canakinumab 150 mg as a subcutaneous (s.c.) injection, and patients with a body weight less than or equal to 40 kg will receive canakinumab 2 mg/kg s.c. Patients will be administered canakinumab every 8 weeks and will undergo an observation period after each dose administration in order to evaluate the response to treatment. Patients who do not achieve complete remission following canakinumab injection in any treatment period will be re-dosed within Day 15 or receive the following dose adjustments:

* 300 mg s.c. (or 4 mg/kg for patients with a body weight less than or equal to 40 kg)
* 450 mg s.c. (or 6 mg/kg for patients with a body weight less than or equal to 40 kg)
* 600 mg s.c. (or 8 mg/kg for patients with a body weight less than or equal to 40 kg)

End of Study will occur when patients discontinue from the study or complete this study. The End of Study visit should occur 8 weeks (plus or minus 1 week) after the last injection. All patients who complete the 6-month evaluation may be offered to enter an extension study (CACZ885D2201E1) conducted to assess long term safety and efficacy data.

Arms: arm 1: Participants received body-weight stratified dosage of canakinumab treatment at 300 milligrams (mg) (for participants weighing more than 40 kilograms (kg)) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 Neonatal-Onset Multisystem Inflammatory Disease (NOMID) participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Interventions: intervention 1: Canakinumab
Intervention descriptions: intervention 1: None

Protocol documents: