Clinical trial NCT00487708: Safety, Efficacy, Pharmacokinetics, Pharmacodynamics of ACZ885 in Patients With NALP3 Mutations and Clinical Symptoms
Official title: An Open-Label, Phase II Dose Titration Study of ACZ885 (Human Anti-IL-1β Monoclonal Antibody) to Assess the Clinical Efficacy, Safety, Pharmacokinetics and Pharmacodynamics in Patients With NALP3 Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NALP3 Mutation
Keywords: ACZ885
NALP3 mutations
Interleukin-1beta
Muckle-Wells Syndrome
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-06-19
Enrollment: 34
Sex: ALL
Minimum age (years): 4
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries.
timeFrame: Every month
Secondary outcomes:
measure: 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
timeFrame: Every month
Other outcomes:
Locations:
city: Lille
country: France
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Dresden
country: Germany
facility: Novartis Investigator Site
city: Heidelberg
country: Germany
facility: Novartis Investigator Site
city: Marburg
country: Germany
facility: Novartis Investigator Site
city: Nuernberg
country: Germany
facility: Novartis investigative site
city: Tuebingen
country: Germany
facility: Novartis Investigator Site
city: New Dehli
country: India
facility: Novartis Investigator Site
city: Oviedo
country: Spain
facility: Novartis Investigator Site
city: London
country: United Kingdom
facility: Novartis Investigative site
Study officials:
affiliation: Investigative site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.