Efficacy and Safety Study of Canakinumab Administered for 6 Months (24 Weeks) in Japanese Patients With Cryopyrin-associated Periodic Syndromes Followed by an Extension Phase

• Register: EUCTR
• Last refreshed on: 18 April 2016
• Main ID: EUCTR2015-003490-15-Outside-EU/EEA
• Date of registration: 14/04/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy and Safety Study of Canakinumab Administered for 6 Months (24 Weeks) in Japanese Patients With Cryopyrin-associated Periodic Syndromes Followed by an Extension Phase
• Scientific title: An Open-label, Efficacy and Safety Study of Canakinumab (Anti-interleukin-1ß Monoclonal Antibody) Administered for 6 Months (24 Weeks) in Japanese Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease, Followed by an Extension Phase to Provide Canakinumab to Study Patients Until it is Approved and Marketed in Japan
• Target sample size: 20
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003490-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Japan

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. At study entry, patients should have a clinical diagnosis of FCAS, MWS or NOMID and require medication. At the time of screening, patients can be either untreated or treated with other medication.
2. Presence, or history of at least 2 of the following symptoms:
- For NOMID patients:
?Typical NOMID urticarial rash
?Signs of central nervous system (CNS) involvement such as increased intracranial pressure and/or papilledema and/or cerebral spinal fluid pleiocytosis and/or stroke and/or seizures, and/or sensorineural hearing loss
?Typical arthropatic changes on X-rays: epiphysal and/or patellar overgrowth With start of NOMID symptoms before or at 6 months of age
- For MWS patients:
?periodic fever
?headache/migraine
?arthralgia
?urticarial skin rash
?conjunctivitis
?myalgia
?sensorineural hearing impairment
- For FCAS patients:
?urticarial skin rash
?fever/chills
?conjunctivitis
?joint pain
3. Patients requiring oral steroids, NSAIDs and/or disease-modifying antirheumatic drugs (DMARDs) can be enrolled if they are on a stable dose (oral steroids: < 20 mg/day or < or = 0.4 mg/kg prednisone or prednisone equivalent, whichever applies) for at least 4 weeks prior to the screening visit.
4. Able to communicate with the investigator and comply with the requirements of the study (for children the parent can assist when necessary).

Other protocol-defined inclusion/exclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or nursing (lactating) women.
2. All women capable of becoming pregnant unless they are postmenopausal or are using one or more methods of contraception.
3. Participation in any other study within 30 days
4. Infection with HIV, Hepatitis B or C.
5. Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
6. History of drug or alcohol abuse within the 12 months prior to dosing.
7. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing for adults.
8. History of significant medical conditions, which in the doctor's opinion would exclude the patient from participating in this trial.
9. History of renal transplantation.
10.Presence of any additional rheumatic diseases or significant systemic diseases. For example, major chronic infectious/ inflammatory/ immunologic disease (such as inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus in addition to the autoinflammatory disease).
11. Presence of any of the following laboratory abnormalities: ALT or AST greater than 2 times the upper limit of normal (ULN), platelet count less than 100x109/L.
12. History of recurrent and/or evidence of clinically significant active bacterial, fungal, or viral infections.
13. History of contact with patients with suspected tuberculosis symptoms; or history or complication of tuberculosis infection.
14. Use of the following therapies:
- Etanercept in the 4 weeks prior to the baseline visit (Day 1) and thereafter
- Adalimumab in the 8 weeks prior to the baseline visit (Day 1) and thereafter
- Infliximab in the 12 weeks prior to the baseline visit (Day 1) and thereafter
- Rituximab in the 26 weeks prior to the baseline visit (Day 1) and thereafter
- Tocilizumab in the 3 weeks prior to the baseline visit (Day 1) and thereafter
- Any other investigational biologics in the 8 weeks prior to the baseline visit (Day 1) and thereafter (with the exception of anakinra therapy-see below)
- Anakinra therapy after the baseline visit (Day 1). Last anakinra injection should occur not less than 6 hours prior to the canakinumab injection at Day 1
- Leflunomide in the 4 weeks prior to the baseline visit (Day 1) and thereafter. After the completion of leflunomide treatment a cholestiramine in dose 8 g 3 times per day for 14 days is recommended.
- Thalidomide in the 4 weeks prior to the baseline visit (Day 1) and thereafter
- Cyclosporine in the 4 weeks prior to the baseline visit (Day 1) and thereafter
- i.v. immunoglobulin (i.v. Ig) in the 8 weeks prior to the baseline visit (Day 1) and thereafter
- 6-Mercaptopurine, azathioprine, cyclophosphamide, or chlorambucil in the 12 weeks prior to the baseline visit (Day 1) and thereafter
- Dapsone, mycophenolate mofetil in the 3 weeks prior to the baseline visit (Day 1) and thereafter
- > or = 20 mg/day or >0.4 mg/kg, whichever applies, of prednisone or prednisone equivalent in the 4 week prior to the baseline visit (Day 1) and thereafter
- Methyl prednisone pulse therapy in the 4 weeks prior to baseline visit and thereafter
15. History of allergic reaction to similar drugs. No additional exclusions may be applied by the doctor, in order to ensure that the study population will be representative of all eligible patients.

Other protocol-defined inclusion/exclusion criteria may apply



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Cryopyrin-associated Periodic Syndromes Familial Cold Autoinflammatory Syndrome Muckle-Wells Syndrome Neonatal Onset Multisystem Inflammatory Disease
MedDRA version: 19.0 Level: PT Classification code 10064570 Term: Familial cold autoinflammatory syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 19.0 Level: LLT Classification code 10064574 Term: NOMID System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 19.0 Level: PT Classification code 10068850 Term: Cryopyrin associated periodic syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 19.0 Level: PT Classification code 10064569 Term: Muckle-Wells syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Ilaris
Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Main Objective: To assess the proportion of patients who were free of relapse at
week 24 including those patients who have been up-titrated.

Primary end point(s): Number of participants without a relapse

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Objective: to assess:
• the safety and tolerability of canakinumab.
• the efficacy of canakinumab with respect to the treatment response (percentage of complete responder patients) by Day 15 for those patients who were not up-titrated and by Day 29 for those patients who were up-titrated.
• the efficacy of canakinumab with respect to physician’s global assessment of auto-inflammatory symptoms.
• the efficacy of canakinumab with respect to inflammatory parameters (CRP, SAA) levels.
• the percentage of patients experiencing a relapse during the entire study.
• the pharmacokinetic (PK) and pharmacodynamic (PD) profiling of canakinumab and assess the PK / PD relationships.
• the clinical improvement (or resolution) with regards to: central nervous system (CNS) involvement, eye disease, hearing impairment, skin disease, joint disease, fever, and kidney
function.
• the change in corticosteroids total daily dose.
• the immunogenicity of canakinumab.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: First point: 29 days
All others: 24 months

Secondary end point(s): •Number of complete responder patients
•Clinical improvement (or resolution) with regards to: central nervous system (CNS) involvement, eye disease, hearing impairment, skin disease, joint disease, fever, and kidney function
•Number of patients experiencing a relapse during the entire study
•How much canakinumab is contained in the patients' blood (pharmacokinetics) and what are the effect of canakinumab on the patients' body (pharmacodynamic)
•Presence of antibody against canakinumab

Secondary ID(s)

NCT00991146

CACZ885D2308

Source(s) of Monetary Support

Novartis Pharmaceuticals