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

Cryopyrin-associated Periodic Syndromes Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01302860
• Other study ID #: CACZ885D2307
• Secondary ID: 2009-016859-22
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2011
• Last updated: July 22, 2015
• Start date: November 2010
• Est. completion date: November 2014

Study information

• Verified date: July 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutSpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyBelgium: Belgian Health Care Knowledge CenterCanada: Health CanadaSwitzerland: SwissmedicUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 60 Months

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cellulitis
• Cryopyrin-Associated Periodic Syndromes
• Eosinophilia
• Familial Cold Autoinflammatory Syndrome
• Muckle-Wells Syndrome
• Neonatal Onset Multisystem Inflammatory Disease
• Syndrome

Intervention

Drug:
• ACZ885

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Laeken
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Le Kremlin Bicetre
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	St. Augustin
Germany	Novartis Investigative Site	Tübingen
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Lausanne
United Kingdom	Novartis Investigative Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Canada,  France,  Germany,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Percentage of Participants Aged 2 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 CRP or SAA to be <15 mg/L and <10 mg/L respectively.	Week 56	No
Secondary	Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56	Participants were assessed based by physician on Physician's Global Assessment measured on a 5--point scale for auto inflammatory disease activity as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.	Week 56	No
Secondary	Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56	Participants were assessed by physician for skin disease (urticarial skin rash) measured on a 5--point scale as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.	Week 56	No
Secondary	Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56	The CRP and SAA were used as inflammatory markers. The target level concentrations for CRP and SAA was =15 mg/L and =10 mg/L, respectively. Negative change in concentration of inflammatory markers indicated improvement.	Baseline, Week 56	No
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.	Day 1 (start of study treatment) up to Week 56 (end of study)	Yes
Secondary	Percentage of Participants Receiving a Concomitant Vaccination During the Study	Participants received any one of the following inactivated vaccines as per the immunization program: Corynebacterium diphtheria, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, Influenza type A, Influenza type B, Haemophilus influenza B, Streptococcus pneumoniae, or Hepatitis B were determined.	Day 1 (start of study treatment) to Week 56 (end of study)	No
Secondary	Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines	Participants who received any inactivated vaccines during the study were assessed for their ability to attain protective antibody levels against the vaccine (antigen) post immunization. Participants vaccinations were not assessed for a response if the antibody titre was already sufficient at pre-dose and maintained during the study.	Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination)	No
Secondary	Number of Participants With Anti-canakinumab Antibodies at Week 56	Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.	Week 56 (End of study)	Yes