An open-label extension study of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations who participated in studies ACZ885G2301 and ACZ885G2305;and response characterization study in canakinumab treatment-naïve patients with active SJIA with and without fever - G2301E1

• Register: EUCTR
• Last refreshed on: 2 February 2015
• Main ID: EUCTR2008-008008-42-AT
• Date of registration: 30/12/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label extension study of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations who participated in studies ACZ885G2301 and ACZ885G2305;and response characterization study in canakinumab treatment-naïve patients with active SJIA with and without fever - G2301E1
• Scientific title: An open-label extension study of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations who participated in studies ACZ885G2301 and ACZ885G2305;and response characterization study in canakinumab treatment-naïve patients with active SJIA with and without fever - G2301E1
• Date of first enrolment: 28/01/2010
• Target sample size: 304
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-008008-42
• 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: Placebo: Other:

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Peru, Poland, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1.Parent’s or legal guardian’s written informed consent and child’s assent, if appropriate, or patient’s informed consent for = 18 years of age before any study related activity is performed.
2.The following patients are eligible to participate in the open label extension study (CACZ885G2301E1):
• Patients from study CACZ885G2305 or CACZ885G2301 who achieved an adapted ACR pediatric 30 response 15 days after their initial dose of canakinumab but clinically deteriorated AS DEFINED BY a minimum ACR Pediatric 30 response not BEING maintained after Day 15 and intervention is deemed necessary by the investigator.
• Patients in study CACZ885G2301 who are not eligible to enter Part II (withdrawal part) because they were not able to meet the corticosteroid entry criteria of 0.5 mg/kg oral prednisone (or equivalent) or were not able to taper their steroids by at least 0.3 mg/kg (please refer to CACZ885G2301 protocol for detailed rules)
• Responder patients in Part I or Part II who were maintaining their minimum ACR pediatric 30 response or had not flared when CACZ885G2301 was stopped.
• CACZ885G2301 patients who were responders in Part I (achieved and maintained a minimum adapted ACR pediatric 30) but experienced a flare in Part II.
• Treatment-naïve patients need to meet the following criteria:
- Confirmed diagnosis of Systemic Juvenile Idiopathic Arthritis as per ILAR definition that must have occured at least 2 months prior to enrollment with onset of disease < 16 years of age
- Male and female patients aged = 2 TO < 20 years of age
- Active disease at the time of enrollment defined as having 2 or more of the following:documented spiking, intermittent fever (body temperature >38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose; at least 2 joints with active arthritis; C-reactive protein (CRP) > 30 mg/l (normal range < 10 MG/L); rash; serositis; lymphadenopathy and hepatosplenomegaly
- Naïve to canakinumab

OTHER PROTOCOL-DEFINED INCLUSION CRITERIA MAY APPLY



Are the trial subjects under 18? yes
Number of subjects for this age range: 288
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
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) female patients
2. Female patients having reached sexual maturity UNLESS they are:
• female patients whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and/or
• using an acceptable method of contraception with a failure rate (Pearl Index (PI)) < 1.
Reliable contraception should be maintained throughout the study and for 3 months after study drug discontinuation.
3. History hypersensitivity to study drug or to biologics.
4. With active or recurrent bacterial, fungal or viral infection at the time of enrollment
5. Risk factors for tuberculosis (TB)
6. With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and/ or places the patient at unacceptable risk for participation in an immunodulatory therapy. In particular, clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty’s syndrome
7. With neutropenia (absolute neutrophil count <1500/mm3) at screening
8. With significant medical conditions, which in the opinion of the Investigator will exclude the patient from the study (can be discussed on a case by case basis with Novartis)
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
10. Live vaccinations within 3 months prior to the start of the study. Killed or inactivated vaccines may be permitted according to the investigator’s discretion.
11. Donation or loss of blood (amount depending on age and weight, 10-20% or more of volume, see Appendix 3 within 8 weeks prior to first dosing, or longer if required by local regulation.
12. Familial and social conditions rendering regular medical assessment not possible
13. History of drug or alcohol abuse within the 12 months prior to dosing.
No additional exclusions may be applied by the investigator, 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

Active systemic manifestations of Systemic Juvenile Idiopathic Arthritis (SJIA)
MedDRA version: 14.1 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: ILARIS
Product Name: Canakinumab
Product Code: ACZ885
Pharmaceutical Form: Powder 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-
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Lyophilisate for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective:

Main Objective: •To assess the long-term safety, tolerability, and immunogenicity of canakinumab
•To assess efficacy at an exploratory level by investigating disease control defined by maintenance of at least an adapted ACR pediatric 30 during the extension PHASE
•To perform biomarker analyses to explore the characteristics of response to canakinumab
treatment
•To introduce Juvenile Arthritis Disease Activity Score (JADAS) and Disease Activity Score
(DAS) as exploratory assessments of efficacy
•To assess efficacy of canakinumab treatment based on adapted pediatric ACR30 criteria in
patients who report previous Anakinra, tocilizumab or other biologic treatment

Primary end point(s): - Long-term safety, tolerability, and immunogenicity of canakinumab
- Disease control by maintenance of at least an adapted ACR pediatric 30
- Assess efficacy of canakinumab treatment based based on adapted ACR Paediatric 30 criteria in patients who report previous anakinra, tocilizumab or other biologic treatment

Timepoint(s) of evaluation of this end point: Days 1 to 728

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Days 1 to 728

Secondary end point(s): 1) The number of patients that were able to taper steroid as per protocol.
2) The number of patients who reached steroid free regimen
3) The number of patients who were able to reduce the canakinumab dose to 2 mg/kg/4 week
4) The percentage of patients who will meet the definition of inactive disease on medication and possible clinical remission on medication

Secondary ID(s)

2008-008008-42-FR

CACZ885G2301E1

Source(s) of Monetary Support

Novartis Pharma AG