Clinical trial NCT01302860: Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
Official title: A One-year Open-label, Multicenter Trial to Assess Efficacy, Safety and Tolerability of Canakinumab (ACZ885) and the Efficacy and Safety of Childhood Vaccinations in Patients Aged 4 Years or Younger With Cryopyrin Associated Periodic Syndromes (CAPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cryopyrin-associated Periodic Syndromes
Familial Cold Autoinflammatory Syndrome
Muckle-Wells Syndrome
Neonatal Onset Multisystem Inflammatory Disease
Keywords: Cryopyrin-associated periodic syndromes (CAPS)
Familial Cold Autoinflammatory Syndrome (FCAS)
Muckle-Wells Syndrome (MWS) or Neonatal Onset Multisystem Inflammatory Disease (NOMID)
children
systemic autoinflammatory disease
CIAS-1 gene
NALP-3
NLRP3
ACZ885
Ilaris
human monoclonal anti-human interleukin-1 beta (IL-beta)
antibody
autosomal dominant
familial autoinflammatory syndrome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-02-24
Enrollment: 17
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial will assess the safety, efficacy and tolerability of ACZ885 in patients aged 4 years and younger with cryopyrin associated periodic syndromes (CAPS)


Eligibility criteria: Inclusion Criteria:

1. Male and female patients that are 28 days up to 60 months of age at the time of the screening visit.
2. Body weight \> or = 2.5 kg.
3. Parent or legal guardian's written informed consent is required before any assessment is performed for patients.
4. At study entry, patients should have a clinical diagnosis of FCAS, MWS, or NOMID and symptoms requiring pharmacological intervention. Prior agreement between the Investigator and Novartis for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed but negative) upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the course of the study.
5. For patients treated with an IL-1 blocking agent (i.e. anakinra, rilonacept), these treatments should be discontinued prior to the baseline visit and patients must demonstrate active disease prior to treatment.
6. Patients who are scheduled to receive an immunization, according to their local vaccination guidelines, with an inactivated vaccine must be willing to participate in the assessment schedule for vaccinated patients.

Exclusion Criteria:

1. Preterm neonates for whom, in the Investigator's judgment, participation in the study is not deemed appropriate.
2. History of recurrent and/or evidence of active bacterial, fungal, or viral infections (including HIV).
3. Patients with immunodeficiency or treatment with immunosuppressive drugs.
4. Live vaccinations within \< or = 3 months prior to screening. No live vaccinations will be allowed throughout the course of this study and up to 3 months following the last dose.
5. Patients with an increased risk of tuberculosis (TB) infection according to following risk factors:

   * Patients with recent close contact with persons known to have active pulmonary TB disease
   * Foreign-born patients from countries with a high prevalence of tuberculosis
   * Patients with recent tuberculosis infection (including children \> 6 months with a positive PPD test \[defined as an induration of at least 10mm\])
   * Patients with end-stage renal disease
   * Patients with diabetes mellitus
   * Patients receiving immunosuppressive therapy
   * Patients with hematologic cancers.
6. Participation in another trial within the last 30 days or 5 half-lives of the investigational compound (whichever is longer).
7. Familial and social conditions rendering regular medical assessment not possible.
8. Pediatric patients with neutropenia (absolute neutrophil count \[ANC\] \< 1.5 x 10 to the 9th/l)

Other protocol defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56
timeFrame: Week 56
Secondary outcomes:
measure: Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56
timeFrame: Week 56
measure: Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56
timeFrame: Week 56
measure: Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56
timeFrame: Week 56
measure: Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56
timeFrame: Baseline, Week 56
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 (start of study treatment) up to Week 56 (end of study)
measure: Percentage of Participants Receiving a Concomitant Vaccination During the Study
timeFrame: Day 1 (start of study treatment) to Week 56 (end of study)
measure: Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
timeFrame: Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination)
measure: Number of Participants With Anti-canakinumab Antibodies at Week 56
timeFrame: Week 56 (End of study)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Laeken
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: St. Augustin
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Brogan PA, Hofer M, Kuemmerle-Deschner JB, Kone-Paut I, Roesler J, Kallinich T, Horneff G, Calvo Penades I, Sevilla-Perez B, Goffin L, Lauwerys BR, Lachmann HJ, Uziel Y, Wei X, Laxer RM. Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger. Arthritis Rheumatol. 2019 Nov;71(11):1955-1963. doi: 10.1002/art.41004. Epub 2019 Sep 9.