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

NCT01302860 | Completed Phase 3 Results DMC

• 2 other identifiers: CACZ885D23072009-016859-22
• Study Type: interventional
• Target: 17
• Locations: 7 countries
• Sites: 12

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)

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56

  Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as C reactive protein (CRP) or Serum amyloid A protein (SAA) to be less than (\<) 15 milligram per liter (mg/L) and \<10 mg/L respectively.

  Week 56

Secondary Outcomes (8)

• Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56

  Week 56

• Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56

  Week 56

• Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56

  Week 56

• Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56

  Baseline, Week 56

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 (start of study treatment) up to Week 56 (end of study)

Study Arms (1)

Canakinumab

EXPERIMENTAL

Canakinumab s.c. injection (2 mg/kg) was administered every 8 weeks.

Drug: ACZ885

Interventions

ACZ885 DRUG

Canakinumab

Eligibility Criteria

• Age: 1 Month - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female patients that are 28 days up to 60 months of age at the time of the screening visit.
• Body weight \> or = 2.5 kg.
• Parent or legal guardian's written informed consent is required before any assessment is performed for patients.
• 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.
• 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.
• 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.

You may not qualify if:

• Preterm neonates for whom, in the Investigator's judgment, participation in the study is not deemed appropriate.
• History of recurrent and/or evidence of active bacterial, fungal, or viral infections (including HIV).
• Patients with immunodeficiency or treatment with immunosuppressive drugs.
• 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.
• 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.
• Participation in another trial within the last 30 days or 5 half-lives of the investigational compound (whichever is longer).
• Familial and social conditions rendering regular medical assessment not possible.
• Pediatric patients with neutropenia (absolute neutrophil count \[ANC\] \< 1.5 x 10 to the 9th/l)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Laken, 1020, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Sankt Augustin, 53757, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Granada, Andalusia, 18012, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Novartis Investigative Site

London, WC1N 1EH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31161734 DERIVED

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes; Multiple Pterygium Syndrome, Autosomal Dominant

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 -778 -8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2011
• First Posted: February 24, 2011
• Study Start: November 1, 2010
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 29, 2017
• Results First Posted: August 18, 2015

Record last verified: 2017-02

Locations

ES (2); GB (1); CH (1); BE (2); FR (1); CA (1); DE (4)