Canakinumab to Treat Neonatal-Onset Multisystem Inflammatory Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 21 June 2021
• Main ID: NCT00770601
• Date of registration: 09/10/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Canakinumab to Treat Neonatal-Onset Multisystem Inflammatory Disease
• Scientific title: A Multi-Center, Open Label, 24-Month Treatment Study to Establish the Safety, Tolerability, Efficacy, Pharmacokinetics of Canakinumab (Anti-IL-1 Beta Antibody) in Patients With NOMID / CINCA Syndrome
• Date of first enrolment: January 26, 2009
• Target sample size: 7
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00770601
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

-INCLUSION CRITERIA:

1. Male and female patients of greater than or equal to 2 years of age at the time of the
screening visit.

2. Patient's informed consent (for greater than or equal to 18 years of age), or in
pediatric patients, parents' or legal guardian's informed consent and patient's assent
to the protocol whenever possible.

3. Females of childbearing potential (young women who have had at least one menstrual
period regardless of age) and/or aged greater than or equal to 8 years must have a
negative serum pregnancy test at screening and a negative urine pregnancy test at each
baseline prior to performance of any radiologic procedure or administration of study
medication.

4. Women of childbearing age and men able to father a child, who are sexually active,
must agree to use a form of effective method of contraception (e.g. birth control
pills, abstinence, double-barrier contraception, etc.) during the study (from the date
of screening) and for at least 3 months following the last dose. Periodic abstinence
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are
not acceptable methods of contraception.

5. Presence, or history (prior to anakinra treatment), of at least 2 of the following
clinical manifestations:

- Typical NOMID urticarial rash.

- Central nervous system (CNS) involvement: increased intracranial pressure
(greater than 180 mm water), papilledema, cerebral spinal fluid pleocytosis
(white cell count greater than 6 cells/mm(3)), stroke, seizures, and/or
sensorineural hearing loss.

- Typical arthropathic changes on X-rays: epiphysial and/or patellar overgrowth.

6. Onset of NOMID/CINCA before or at 6 months of age.

7. Patients requiring oral steroids, NSAIDs and/or disease-modifying antirheumatic drugs
(DMARDs) can be enrolled if they are on a stable dose (oral steroids: less than 20
mg/day or less than or equal to 0.4 mg/kg prednisone or prednisone equivalent,
whichever applies) for at least 4 weeks prior to the screening visit. Steroid therapy
may be tapered during treatment with canakinumab after the first canakinumab treatment
period / cycle, at the discretion of the investigator.

8. Negative tuberculin skin test reaction (PPD 5 tuberculin units or as according to
local standard practice) (less than 5mm induration) at 48 to 72 hours after
administration at the screening visit or within 2 months prior to the screening visit,
according to national guidelines. Patients who have a positive PPD skin test with a
documentation of BCG vaccination, who are at low environmental risk for tuberculosis
(TB) infection or reactivation, and have a negative chest X-ray can be included. A
positive PPD test will be defined using the MMWR 2000 guidance, summarized as criteria
for tuberculin positivity by risk group.

9. Able to comply with the requirements of the study.

EXCLUSION CRITERIA:

Subjects meeting any of the following criteria will be excluded from entry into or
continuation in the study unless sponsor approval is obtained:

1. Pregnant or breastfeeding women.

2. Participation in any clinical trial investigation within 4 weeks prior to dosing or
longer if required by local regulation, with the exception of trials with anakinra
and/or canakinumab.

3. In case of previous treatment with biologic agents or DMARDs, an appropriate washout
period (as according to the recognized duration of effect and half lives) will be
required for such patients to be eligible to participate in the trial, e.g.:

Previous treatment and required washout period prior to baseline and thereafter:

- Rituximab, 26 weeks

- Infliximab, 12 weeks

- Adalimumab, 8 weeks

- Etanercept, 4 weeks

- Anakinra, 1 day

- Any other investigational biologics, 8 weeks

- Leflunomide, 4 weeks

- Thalidomide, 4 weeks

- Cyclosporine, 4 weeks

- i.v. immunoglobulin (i.v. Ig), 8 weeks

- Dapsone, mycophenolate mofetil, 3 weeks

- Corticosteroids greater than or equal to 20 mg/day or greater than 0.4 mg/kg
prednisone or prednisone equivalent, whichever applies, 1 week

4. Donation or loss of 300 mL or more of blood within 8 weeks prior to dosing.

5. A past medical history of clinically significant ECG abnormalities or a family history
of a prolonged QT-interval syndrome.

6. History of immunocompromise.

7. Positive test for or prior history of HIV (ELISA and Western blot), Hepatitis B
(Hepatitis B surface antigen) or Hepatitis C.

8. Presence of active infections or a history of pulmonary TB infection with or without
documented adequate therapy. Subjects with current active TB, or recent close exposure
to an individual with active TB are excluded from the study.

9. 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, systemic lupus
erythematosus in addition to the autoinflammatory disease).

10. Treatment with a live virus vaccine during 3 months prior to baseline visit. No live
vaccines will be allowed throughout the course of this study and up to 3 months
following the last dose.

11. History of renal transplant.

12. 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.

13. Presence of any of the following laboratory abnormalities: ALT or AST greater than 2
times the upper limit of normal (ULN), platelet count less than 100x10(9)/L.



Age minimum: 2 Years
Age maximum: 25 Years
Gender: All

Health Condition(s) or Problem(s) studied

NOMID

CINCA Syndrome

Intervention(s)

Drug: Canakinumab

Primary Outcome(s)

Percentage of Participants With Complete Remission and Relapse After 6 Months of Canakinumab Treatment. [Time Frame: 6 months]

Secondary ID(s)

09-AR-0006

CACZ885D2201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Results

• Results available: Yes
• Date Posted: 10/06/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00770601