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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I, Part II-arm1, & Part III | Experimental |
| |
| Part II - arm 2 | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACZ885 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Response in Part I (After 8 Weeks) | Treatment response was based on Physician's global assessment(PGA) of autoinflammatory disease activity, assessment of skin disease(SD) and serum values of C-reactive protein(CRP) and/or serum amyloid A(SAA). Complete Response (CR):PGA and SD ≤ minimal and normal CRP and/or SAA. Partial Response (PR): a reduction of CRP and/or SAA from baseline (BL) by >30% but not reaching normal values and PGA improvement from BL by at least one category. Disease flare: a CRP and/or SAA > 30 mg/L and either PGA > minimal or PGA = minimal and SD > minimal. Non-responders = no PR by Day 8 or no CR by Day 15. |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | San Francisco | California | 94115 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22152723 | Derived | 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. | |
| 19494217 |
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| ID | Title | Description |
|---|---|---|
| FG000 | ACZ885 | ACZ885 150 mg subcutaneous injection or 2 mg/kg subcutaneous injection, depending on body weight, every 8 weeks. |
| FG001 | Placebo | Placebo subcutaneous injection every 8 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part I - Open-label Treatment Period |
|
| ||||||||||||||||||
| Part II - 1:1 ACZ885:Placebo |
| |||||||||||||||||||
| Part III - Open-label Treatment Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ACZ885 | ACZ885 150 mg subcutaneous injection or 2 mg/kg subcutaneous injection, depending on body weight, every 8 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | percent of participants | 32 weeks after study start |
|
48 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part I ACZ885 | ACZ885 150 mg subcutaneous injection or 2 mg/kg subcutaneous injection, depending on body weight, every 8 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
The outcomes for this study were reported in separate tables for each period. The SAE and AEs were reported in all in one table.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D056587 | Cryopyrin-Associated Periodic Syndromes |
| C566739 | Multiple Pterygium Syndrome, Autosomal Dominant |
| ID | Term |
|---|---|
| D056660 | Hereditary Autoinflammatory Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
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| ID | Term |
|---|---|
| C541220 | canakinumab |
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|
| 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) | A 5-point scale was used for the Physician's global assessment on autoinflammatory disease activity (absent, minimal, mild, moderate and severe) and for the assessment of the following items:
| 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)) | Assessed serum clearance of ACZ885. | 48 weeks after study start |
| Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I. | until Week 8 |
| Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II. | 32 weeks after study start |
| Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III. | 48 weeks after study start |
| Chicago |
| Illinois |
| 60612 |
| United States |
| Novartis Investigative Site | Madison | Wisconsin | 53792 | United States |
| Novartis Investigative Site | Le Kremlin-Bicêtre | France |
| Novartis Investigational Site | Lille | France |
| Novartis Investigative Site | Montpellier | France |
| Novartis Investigative Site | Nantes | France |
| Novartis Investigative Site | Paris | France |
| Novartis Investigative Site | Tübingen | Germany |
| Novartis Investigative Site | New Delhi | India |
| Novartis Investigative Site | Barcelona | Spain |
| Novartis Investigative Site | London | United Kingdom |
| 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. |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Number of Participants With Treatment Response in Part I (After 8 Weeks) | Treatment response was based on Physician's global assessment(PGA) of autoinflammatory disease activity, assessment of skin disease(SD) and serum values of C-reactive protein(CRP) and/or serum amyloid A(SAA). Complete Response (CR):PGA and SD ≤ minimal and normal CRP and/or SAA. Partial Response (PR): a reduction of CRP and/or SAA from baseline (BL) by >30% but not reaching normal values and PGA improvement from BL by at least one category. Disease flare: a CRP and/or SAA > 30 mg/L and either PGA > minimal or PGA = minimal and SD > minimal. Non-responders = no PR by Day 8 or no CR by Day 15. | Posted | Number | Participants | 8 weeks after study start |
|
|
|
| Secondary | 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) | A 5-point scale was used for the Physician's global assessment on autoinflammatory disease activity (absent, minimal, mild, moderate and severe) and for the assessment of the following items:
| Posted | Number | Participants | 32 weeks after study start |
|
|
|
| Secondary | 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. | Intention to treat (ITT)population and LOCF. | Posted | Mean | Standard Deviation | mg/L | Week 8 and Week 32 |
|
|
|
| Secondary | Pharmacokinetics (CLD (L/d)) | Assessed serum clearance of ACZ885. | Patients in Part I and Part II who received at least one dose of ACZ885. | Posted | Mean | Standard Deviation | L/day | 48 weeks after study start |
|
|
|
| Primary | 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. | Posted | Number | Participants | 32 weeks after study start |
|
|
|
| Secondary | Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I. | Intention to treat (ITT) population. | Posted | Mean | Standard Deviation | pg/mL | until Week 8 |
|
|
|
| Secondary | Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II. | Intention to treat (ITT) population. | Posted | Mean | Standard Deviation | pg/mL | 32 weeks after study start |
|
|
|
| Secondary | Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III. | Intention to treat (ITT) population. | Posted | Mean | Standard Deviation | pg/mL | 48 weeks after study start |
|
|
|
| 0 |
| 35 |
| 27 |
| 35 |
| EG001 | Part II ACZ885 | ACZ885 150 mg subcutaneous injection or 2 mg/kg subcutaneous injection, depending on body weight, every 8 weeks. | 0 | 15 | 15 | 15 |
| EG002 | Part II Placebo | Placebo subcutaneous injection every 8 weeks. | 0 | 16 | 14 | 16 |
| EG003 | Part III ACZ885 | ACZ885 150 mg subcutaneous injection or 2 mg/kg subcutaneous injection, depending on body weight, every 8 weeks. | 2 | 31 | 24 | 31 |
| EG004 | Entire Study ACZ885 | Entire study ACZ885. The SAE and AEs were collected and reported for all three periods. | 2 | 35 | 35 | 35 |
| Blindness unilateral | Eye disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Intraocular pressure increased | Investigations | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Stomach discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Tooth impacted | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Hangover | General disorders | MedDRA | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Allergy to arthropod bite | Immune system disorders | MedDRA | Systematic Assessment |
|
| House dust allergy | Immune system disorders | MedDRA | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tinea pedis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Face injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Complex regional pain syndrome | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Nystagmus | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Stress | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Allergic cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D000094482 | Chronic Inducible Urticaria |
| D000080223 | Chronic Urticaria |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D000096703 | Cold Urticaria |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Non-responder (protocol violation) |
|
| Mild |
|
| Moderate |
|
| Severe |
|