Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease

NCT00685373 | Completed Phase 3 Results

• 1 other identifier: CACZ885D2306
• Study Type: interventional
• Target: 166
• Locations: 9 countries
• Sites: 28

Brief Summary

This will provided long-term safety and efficacy data for ACZ885 (a fully human anti-interleukin-1β \[anti-IL-1β\] monoclonal antibody) given as an injection subcutaneously in patients who participated in the CACZ885A2102 (NCT00487708), CACZ885D2201 (NCT00685373) or CACZ885D2304(NCT00465985) studies or newly identified patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome or Neonatal Onset Multisystem Inflammatory Disease. The duration of this study was 6 months with a maximum duration of 2 years

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),; MWS with overlapping symptoms of Neonatal Onset Multisystem Inflammatory Disease (NOMID) or Neonatal Onset Multisystem Inflammatory Disease (NOMID),; children,; systemic autoinflammatory disease,; CIAS-1 gene,; NALP-3,; ACZ885,; human monoclonal anti-human interleukin-1beta (IL-1beta),; antibody,; autosomal dominant,; familial autoinflammatory syndrome

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions

  The number of participants with Adverse Events and Infections \& Infestations are regardless of study drug relationship by primary system organ class preferred term equal and/or greater than 2% in any group. The number of participants with mild injection site reactions= mild reactions observed on at least one occasion but no moderate or severe reactions. The number of participants with moderate injection site reactions= moderate reactions observed on at least one occasion but no severe reactions.

  2 years depending on when the participant enters the study

Secondary Outcomes (3)

• The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers.

  Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

• Immunogenicity of Canakinumab (ACZ885)

  Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

• Pharmacokinetics

  Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

Study Arms (1)

Canakinumab (ACZ885)

EXPERIMENTAL

Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Drug: Canakinumab (ACZ885)

Interventions

Canakinumab (ACZ885) DRUG

6 mL glass vial containing 150 mg lyophilized Canakinumab reconstituted with water for a subcutaneous injection every 8 weeks. Dosage based on body weight.

Canakinumab (ACZ885)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients at least 3 years of age
• Diagnosis of Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome or Neonatal Onset Multisystem Inflammatory Disease. 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 under anakinra therapy or any other investigational IL-1 blocking therapy, these treatments should be discontinued prior to the baseline visit.
• Patients from the CACZ885A2102 study may enter this study. However, dosing at Visit 2 (Baseline Visit) can only occur if either 1) the patient is experiencing disease flare or 2) at least two months have elapsed from their last injection even in the absence of flare, whichever is earlier.
• Patients who completed the CACZ885D2304 study may enter this study
• Patients who completed the CACZ885D2201 study may enter this study
• Patients who discontinued from the CACZ885A2102, CACZ885D2201 or CACZ885D2304 studies and for whom in the Investigator's judgment (with prior agreement from Novartis) continued treatment with ACZ885 in this study is considered appropriate.

You may not qualify if:

• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation with the exception of trials with anakinra, other investigational IL-1 blocking therapies, and/or ACZ885.
• History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result is not allowed.
• No live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
• History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
• Positive tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice) (\>= 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit. 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (28)

Little Rock Allergy and Asthma Clinic

Little Rock, Arkansas, 72205, United States

Location

UCSF School of Medicine

San Francisco, California, 94118, United States

Location

Allergy Center at Brookstone

Columbus, Georgia, 31904, United States

Location

Rush-Presbyterian St. Lukes Medical Center

Chicago, Illinois, 60612, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Laken, Belgium

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, France

Location

Novartis Investigative Site

Lille, France

Location

Novartis Investigative Site

Montpelier Cedex, France

Location

Novartis Investigative site

Nantes, France

Location

Novartis Investigative site

Berlin, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative site

Heidelberg, Germany

Location

Novartis Investigative Site

Herne, Germany

Location

Novartis Investigative Site

Marburg, Germany

Location

Novartis Investigative site

Tübingen, Germany

Location

Novartis Investigative site

New Delhi, India

Location

Novartis Investigative site

Genova, Italy

Location

Novartis Investigative Site

Napoli, Italy

Location

Novartis Investigative Site

Padua, Italy

Location

Novartis Investigative Site

Rome, Italy

Location

Novartis Investigative Site

Trieste, Italy

Location

Novartis Investigative Site

Madrid, Spain

Location

Novartis Investigative site

Oviedo, Spain

Location

Novartis Investigative Site

Vigo, Spain

Location

Novartis Investigative site

Istanbul, Turkey (Türkiye)

Location

Novartis Investigative site

London, United Kingdom

Location

Related Publications (1)

• Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, Hoyer J, Gattorno M, Gul A, Smith J, Leslie KS, Jimenez S, Morell-Dubois S, Davis N, Patel N, Widmer A, Preiss R, Lachmann HJ. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011 Dec;70(12):2095-102. doi: 10.1136/ard.2011.152728. Epub 2011 Aug 21.

  PMID: 21859692 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

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: May 27, 2008
• First Posted: May 28, 2008
• Study Start: May 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: November 4, 2016
• Results First Posted: May 27, 2011

Record last verified: 2016-09

Locations

DE (6); TU (1); US (6); BE (1); FR (4); IT (5); IN (1); GB (1); ES (3)