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

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ClinicalTrials.gov Identifier: NCT01576367
Recruitment Status : Completed
First Posted : April 12, 2012
Results First Posted : August 3, 2016
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Primary Purpose: Treatment
Conditions Cryopyrin-associated Periodic Syndromes
Familial Cold Autoinflammatory Syndrome
Muckle-Wells Syndrome
Neonatal Onset Multisystem Inflammatory Disease
Intervention Biological: ACZ885
Enrollment 17
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Canakinumab
Hide Arm/Group Description Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Period Title: Overall Study
Started 17
Completed 14
Not Completed 3
Reason Not Completed
Unsatisfactory therapeutic effect             2
Moved to commercial use after 6 months             1
Arm/Group Title Canakinumab
Hide Arm/Group Description Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age at start of extension study (years) Number Analyzed 17 participants
3.1  (1.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
5
  29.4%
Male
12
  70.6%
1.Primary Outcome
Title The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Serological Inflammation Markers.
Hide Description Disease relapse following complete response is defined as inflammation markers: C-Reactive Protein (CRP) and/or Serum Amyloid A (SAA) result > 30 mg/L AND Physician's Global Assessment of Autoinflammatory Disease Activity > minimal or Physician's Global Assessment >= minimal AND Skin Disease Assessment > minimal. Physician's Global Assessment of Autoinflammatory Disease Activity and Skin Disease Assessment (urticarial skin rash) are completed by the investigator using a 5 point rating scale: absent, minimal, mild, moderate and severe.
Time Frame Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Extension Full analysis set (FAS) consisted of all patients who received at least one dose of study drug in the extension study
Arm/Group Title Canakinumab
Hide Arm/Group Description:
Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Percentage of participants
94.1
2.Secondary Outcome
Title Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies
Hide Description Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.
Time Frame minimum of 6 months and maximum of 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Extension Safety set consisted of all patients from the core study who received at least one dose of study drug in the extension study and had at least one post-treatment safety assessment. Of note, the statement that a patient had no AE also constituted a safety assessment.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: Participants
0
3.Secondary Outcome
Title Change From Baseline (Core Study Baseline) in C­-Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations
Hide Description CRP and SAA were used as serologic inflammatory markers. The target level concentrations for CRP and SAA was ≤15 mg/L and ≤10 mg/L, respectively. Negative change in concentration of inflammatory markers indicated improvement.
Time Frame Week 0, 80, 104, 128 and 152, last assessment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Extension Full analysis set (FAS) consisted of all patients who received at least one dose of study drug in the extension study
Arm/Group Title Canakinumab
Hide Arm/Group Description:
Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: (mg/L)
CRP at Core End of Study (last assessment) (n=14) -5.4  (6.28)
CRP at week 80 (n=16) -14.7  (35.8)
CRP at Week 104 (n=11) -3.8  (14.4)
CRP at Week 128(n=12) -4.1  (10.3)
CRP at Week 152 (n=12) -4.3  (11)
CRP at End of Study (last assessment) (n=16) -10.4  (30.3)
SAA at Core End of Study (last assessment) (n=16) -54.4  (133.8)
SAA at Week 80 (n=12) -79.1  (224.1)
SAA at week 104 (n=11) 15.8  (158.1)
SAA at week 128 (n=10) -28.2  (47.4)
SAA at week 152 (n=11) -6.4  (60.0)
SAA at End of Study (last assessment) (n=15) -58.5  (183.6)
4.Secondary Outcome
Title Frequency Counts of Physician’s Global Assessment of Autoinflammatory Disease and Skin Disease
Hide Description Participants were assessed based by physician on Physician's Global Assessment measured on a 5­-point scale for auto inflammatory disease activity as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe
Time Frame minimum of 6 months and maximum of 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Extension Full analysis set (FAS) consisted of all patients who received at least one dose of study drug in the extension study
Arm/Group Title Canakinumab
Hide Arm/Group Description:
Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Percentage of participants
Assessment of autoinflammatory disease (Absent) 64.7
Assessment of autoinflammatory disease (Minimal) 29.4
Assessment of autoinflammatory disease (Mild) 5.9
Assessment of autoinflammatory disease (Moderate) 0
Assessment of autoinflammatory disease (Severe) 0
Assessment of skin disease (Absent) 94.1
Assessment of skin disease (Minimal) 0
Assessment of skin disease (Mild) 5.9
Assessment of skin disease (Moderate) 0
Assessment of skin disease (Severe) 0
5.Secondary Outcome
Title Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
Hide Description Participants who received any inactivated vaccines during the study were assessed for their ability to attain protective antibody levels against the vaccine (antigen) post immunization. Participants vaccinations were not assessed for a response if the antibody titre was already sufficient at pre-dose and maintained during the study.
Time Frame pre-vaccine dose, Day 28 post-vaccine
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Extension Full analysis set (FAS) consisted of all patients who received at least one dose of study drug in the extension study. Out of 20 unique patient-vaccination cases, 17 cases were assessable for a vaccination response due to availability of pre dose antibody titer.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
Overall Number of Participants Analyzed 4
Overall Number of Units Analyzed
Type of Units Analyzed: Patient-vaccination cases
17
Measure Type: Number
Unit of Measure: vaccination cases
Positive response for antibody levels 16
No pre-dose antibody levels 3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Canakinumab
Hide Arm/Group Description Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks)
All-Cause Mortality
Canakinumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Canakinumab
Affected / at Risk (%)
Total   8/17 (47.06%) 
Ear and labyrinth disorders   
Conductive deafness  1  1/17 (5.88%) 
Gastrointestinal disorders   
Abdominal pain  1  1/17 (5.88%) 
Vomiting  1  1/17 (5.88%) 
General disorders   
Papillitis  1  1/17 (5.88%) 
Infections and infestations   
Bronchitis  1  1/17 (5.88%) 
Meningitis aseptic  1  1/17 (5.88%) 
Pneumonia  1  2/17 (11.76%) 
Injury, poisoning and procedural complications   
Limb injury  1  1/17 (5.88%) 
Vascular disorders   
Haematoma  1  1/17 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Canakinumab
Affected / at Risk (%)
Total   16/17 (94.12%) 
Blood and lymphatic system disorders   
Eosinophilia  1  1/17 (5.88%) 
Cardiac disorders   
Angina pectoris  1  1/17 (5.88%) 
Congenital, familial and genetic disorders   
Cryopyrin associated periodic syndrome  1  1/17 (5.88%) 
Ear and labyrinth disorders   
Conductive deafness  1  1/17 (5.88%) 
Ear pain  1  2/17 (11.76%) 
Eye disorders   
Eye pruritus  1  1/17 (5.88%) 
Iridocyclitis  1  1/17 (5.88%) 
Papilloedema  1  2/17 (11.76%) 
Uveitis  1  1/17 (5.88%) 
Gastrointestinal disorders   
Abdominal pain  1  2/17 (11.76%) 
Abdominal pain upper  1  2/17 (11.76%) 
Aphthous stomatitis  1  2/17 (11.76%) 
Diarrhoea  1  7/17 (41.18%) 
Gingival hypertrophy  1  1/17 (5.88%) 
Mouth ulceration  1  3/17 (17.65%) 
Nausea  1  2/17 (11.76%) 
Toothache  1  1/17 (5.88%) 
Vomiting  1  6/17 (35.29%) 
General disorders   
Pyrexia  1  6/17 (35.29%) 
Immune system disorders   
Milk allergy  1  1/17 (5.88%) 
Seasonal allergy  1  1/17 (5.88%) 
Infections and infestations   
Abscess limb  1  1/17 (5.88%) 
Bronchitis  1  2/17 (11.76%) 
Cellulitis  1  1/17 (5.88%) 
Cystitis  1  1/17 (5.88%) 
Ear infection  1  3/17 (17.65%) 
Eczema infected  1  1/17 (5.88%) 
Enterobiasis  1  1/17 (5.88%) 
Gastroenteritis  1  4/17 (23.53%) 
Hand-foot-and-mouth disease  1  1/17 (5.88%) 
Impetigo  1  2/17 (11.76%) 
Laryngitis  1  1/17 (5.88%) 
Lice infestation  1  1/17 (5.88%) 
Meningitis aseptic  1  1/17 (5.88%) 
Molluscum contagiosum  1  2/17 (11.76%) 
Nasopharyngitis  1  7/17 (41.18%) 
Oral herpes  1  1/17 (5.88%) 
Otitis media  1  1/17 (5.88%) 
Paronychia  1  2/17 (11.76%) 
Pharyngitis streptococcal  1  1/17 (5.88%) 
Pneumonia  1  1/17 (5.88%) 
Rhinitis  1  4/17 (23.53%) 
Tonsillitis  1  3/17 (17.65%) 
Upper respiratory tract infection  1  4/17 (23.53%) 
Urinary tract infection  1  2/17 (11.76%) 
Varicella  1  3/17 (17.65%) 
Vulval abscess  1  1/17 (5.88%) 
Injury, poisoning and procedural complications   
Arthropod bite  1  1/17 (5.88%) 
Craniocerebral injury  1  1/17 (5.88%) 
Investigations   
Body temperature increased  1  1/17 (5.88%) 
C-reactive protein increased  1  1/17 (5.88%) 
CSF white blood cell count increased  1  1/17 (5.88%) 
Serum amyloid A protein increased  1  1/17 (5.88%) 
Transaminases increased  1  1/17 (5.88%) 
Tympanometry abnormal  1  2/17 (11.76%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders   
Joint swelling  1  1/17 (5.88%) 
Pain in extremity  1  1/17 (5.88%) 
Nervous system disorders   
Burning sensation  1  1/17 (5.88%) 
Cerebral ventricle dilatation  1  1/17 (5.88%) 
Headache  1  6/17 (35.29%) 
Hemiplegia  1  1/17 (5.88%) 
Lethargy  1  1/17 (5.88%) 
Loss of consciousness  1  1/17 (5.88%) 
Motor developmental delay  1  2/17 (11.76%) 
Pyramidal tract syndrome  1  1/17 (5.88%) 
Seizure  1  1/17 (5.88%) 
Speech disorder developmental  1  3/17 (17.65%) 
Renal and urinary disorders   
Hypertonic bladder  1  1/17 (5.88%) 
Reproductive system and breast disorders   
Breast pain  1  1/17 (5.88%) 
Vulvovaginal burning sensation  1  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/17 (29.41%) 
Epistaxis  1  1/17 (5.88%) 
Oropharyngeal pain  1  3/17 (17.65%) 
Productive cough  1  1/17 (5.88%) 
Rhinorrhoea  1  1/17 (5.88%) 
Skin and subcutaneous tissue disorders   
Dermatitis  1  1/17 (5.88%) 
Dermatitis diaper  1  1/17 (5.88%) 
Dry skin  1  1/17 (5.88%) 
Eczema  1  2/17 (11.76%) 
Hypersensitivity vasculitis  1  1/17 (5.88%) 
Prurigo  1  1/17 (5.88%) 
Pruritus  1  1/17 (5.88%) 
Pruritus generalised  1  1/17 (5.88%) 
Rash  1  5/17 (29.41%) 
Rash maculo-papular  1  1/17 (5.88%) 
Skin lesion  1  1/17 (5.88%) 
Urticaria  1  1/17 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01576367     History of Changes
Other Study ID Numbers: CACZ885D2307E1
2011-005154-57 ( EudraCT Number )
First Submitted: February 17, 2012
First Posted: April 12, 2012
Results First Submitted: June 22, 2016
Results First Posted: August 3, 2016
Last Update Posted: September 11, 2018