Safety, Efficacy, Pharmacokinetics, Pharmacodynamics of ACZ885 in Patients With NALP3 Mutations and Clinical Symptoms

NCT00487708 | Completed Phase 2 DMC

• 1 other identifier: CACZ885A2102
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 10

Brief Summary

This study will investigate the clinical efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ACZ885, administered intravenously and subcutaneously to patients with NALP3 mutations whose clinical symptoms are either untreated or insufficiently treated and require medical intervention.

Conditions

NALP3 Mutation

Keywords

ACZ885; NALP3 mutations; Interleukin-1beta; Muckle-Wells Syndrome

Outcome Measures

Primary Outcomes (1)

• Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries.

  Every month

Secondary Outcomes (1)

• Assessment of safety,tolerability and immunogenicity of ACZ885 at each clinical visit. Evaluation of ACZ885 PK and PD at each clinical visit Evaluate efficacy towards hearing loss(every 4 months),kidney function (every 4 months),neurological symptoms

  Every month

Study Arms (1)

1

EXPERIMENTAL

ACZ885

Drug: canakinumab

Interventions

canakinumab DRUG

1

Eligibility Criteria

• Age: 4 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 4 to 75 years (inclusive)
• Body weight ≥ 12 kg and \< 100 kg.
• Females of child-bearing potential must have a negative pregnancy test. Additional birth control details to be provided at screening.
• Documented molecular diagnosis of NALP3 mutations and clinical symptoms that are either untreated or insufficiently treated and require medical intervention.
• Patients under anakinra therapy or any other IL-1 blocking therapy, whose clinical symptoms improved under treatment and are willing to discontinue that therapy until a relapse becomes evident.
• Patients with a very severe characteristics requiring oral prednisone are eligible if the dose is stable (≤ 0.4 mg/kg/day or ≤ 20 mg/day, whichever is lower) for at least 1 week prior to the screening visit. Steroid therapy may be tapered during treatment with ACZ885 at the discretion of the investigator.
• Parents' or legal guardian's written informed consent (patient's informed consent for ≥ 18 years of age) and child's assent, if appropriate, are required prior to study participation.

You may not qualify if:

• Participation in any clinical trial investigation (except trials with anakinra) within 4 weeks prior to dosing or longer per local regulation
• Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. Therapeutic antibodies (e.g. anti-TNF-alpha antibodies) must be discontinued at least 60 days before dosing.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• A past personal or close family medical history of clinically significant ECG abnormalities or prolonged QT-interval syndrome.
• History of
• Immunocompromise, including a positive HIV result.
• Positive Hepatitis B surface antigen or Hepatitis C test result.
• Drug or alcohol abuse within the 12 months prior to dosing.
• Tuberculosis.
• Renal transplant.
• Evidence of lymphoma.
• Active medical condition preventing participation in the study such as infection, poorly controlled diabetes etc.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigator Site

Lille, France

Location

Novartis Investigator Site

Berlin, Germany

Location

Novartis Investigator Site

Dresden, Germany

Location

Novartis Investigator Site

Heidelberg, Germany

Location

Novartis Investigator Site

Marburg, Germany

Location

Novartis investigative site

Nuremberg, Germany

Location

Novartis Investigator Site

Tübingen, Germany

Location

Novartis Investigator Site

New Dehli, India

Location

Novartis Investigator Site

Oviedo, Spain

Location

Novartis Investigative site

London, United Kingdom

Location

Related Publications (1)

• Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, Stricker K, Chakraborty A, Tannenbaum S, Wright AM, Rordorf C. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011 Feb 28;13(1):R34. doi: 10.1186/ar3266.

  PMID: 21356079 DERIVED

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes

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

Study Officials

• Novartis

  Investigative site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 18, 2007
• First Posted: June 19, 2007
• Study Start: January 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: February 17, 2009

Record last verified: 2009-02

Locations

IN (1); GB (1); FR (1); DE (6); ES (1)