Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome

NCT00465985 | Completed Phase 3 Results

• 1 other identifier: CACZ885D2304
• Study Type: interventional
• Target: 35
• Locations: 6 countries
• Sites: 12

Brief Summary

This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome. Part I is an 8-week open-label, active treatment period to identify ACZ885 responders. Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo. Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.

Conditions

Muckle Wells Syndrome

Keywords

Muckle-Wells Syndrome; 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 (2)

• Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)

  Determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Data expressed as a percent of participants who had experienced a flare by the end of Part II.

  32 weeks after study start

• Number of Participants Who Experienced a Disease Flare in Part II

  Disease flare is determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Disease Flare = the C-reactive protein and/or serum amyloid A (SAA) \> 30 mg/L and either a PGA \> minimal, or PGA equal to minimal and \> minimal SD.

  32 weeks after study start

Secondary Outcomes (7)

• Number of Participants With Treatment Response in Part I (After 8 Weeks)

  8 weeks after study start

• Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part)

  32 weeks after study start

• Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8.

  Week 8 and Week 32

• Pharmacokinetics (CLD (L/d))

  48 weeks after study start

• Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.

  until Week 8

Study Arms (2)

Part I, Part II-arm1, & Part III

EXPERIMENTAL

Drug: ACZ885

Part II - arm 2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ACZ885 DRUG

Part I, Part II-arm1, & Part III

Placebo DRUG

Part II - arm 2

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:

• Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
• Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare
• Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).

You may not qualify if:

• History of being immunocompromised, including a positive HIV at screening test result.
• 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 significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
• History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
• Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.

Sponsors & Collaborators

• Novartis: lead

Study Sites (12)

Novartis Investigative Site

San Francisco, California, 94115, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, France

Location

Novartis Investigational Site

Lille, France

Location

Novartis Investigative Site

Montpellier, France

Location

Novartis Investigative Site

Nantes, France

Location

Novartis Investigative Site

Paris, France

Location

Novartis Investigative Site

Tübingen, Germany

Location

Novartis Investigative Site

New Delhi, India

Location

Novartis Investigative Site

Barcelona, Spain

Location

Novartis Investigative Site

London, United Kingdom

Location

Related Publications (2)

• Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, Ferreira A, Lheritier K, Patel N, Preiss R, Hawkins PN; Canakinumab in CAPS Study Group. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. doi: 10.1186/ar3535. Epub 2011 Dec 9.

  PMID: 22152723 DERIVED

• Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. doi: 10.1056/NEJMoa0810787.

  PMID: 19494217 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

Limitations and Caveats

The outcomes for this study were reported in separate tables for each period. The SAE and AEs were reported in all in one table.

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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2007
• First Posted: April 27, 2007
• Study Start: April 1, 2007
• Primary Completion: October 1, 2008
• Last Updated: August 28, 2017
• Results First Posted: February 11, 2011

Record last verified: 2017-07

Locations

IN (1); DE (1); ES (1); GB (1); FR (5); US (3)