A Multi-Center, Open label, Repeated Dose Range Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Efficacy of an Anti-IL-1ß Monoclonal Antibody (ACZ885) Given Subcutaneously in Pediatric Subjects with Active Systemic Juvenile Idiopathic Arthritis (SJIA) - CACZ885A2203

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2006-001834-42-GB
• Date of registration: 14/10/2010
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Multi-Center, Open label, Repeated Dose Range Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Efficacy of an Anti-IL-1ß Monoclonal Antibody (ACZ885) Given Subcutaneously in Pediatric Subjects with Active Systemic Juvenile Idiopathic Arthritis (SJIA) - CACZ885A2203
• Scientific title: A Multi-Center, Open label, Repeated Dose Range Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Efficacy of an Anti-IL-1ß Monoclonal Antibody (ACZ885) Given Subcutaneously in Pediatric Subjects with Active Systemic Juvenile Idiopathic Arthritis (SJIA) - CACZ885A2203
• Date of first enrolment: 27/04/2007
• Target sample size: 26
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001834-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; Other trial design description: Parallel groups in stage I; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects aged 4 to 20 years at the time of the screening visit, having passed screening examinations. Parents’ or legal guardian’s written informed consent (patient’s informed consent for = 18 years of age) and child’s assent, if appropriate, are required prior to study participation. 2. Female subjects of child-bearing potential may participate if they have a negative serum pregnancy test at screening and prior to dosing, and are willing to practice double-barrier contraception during the study (from the date of screening) and for at least 3 months following the last dose. 3. Patient meets the diagnostic criteria for SJIA and has active disease defined as active arthritis (using ACR definition of active joint) in at least one joint for the last 6 weeks (does not have to be the same joint) and within 2 weeks of study entry at least one of the following systemic features considered by the treating physician to be due to SJIA: spiking, intermittent fever (body temperature > 38.9 C only for several hours during the day), and CRP > 50 mg/L (normal range < 10 mg/L). 4. Anakinra naïve or willing to discontinue anakinra under close monitoring (run in phase) until relapse (reappearance of fever and/or CRP increase). 5. Able to discontinue second line agent such as disease-modifying and immunosuppressive drugs, not including methotrexate and corticosteroids. 6. If part of the treatment at screening visit: Stable dose of methotrexate (maximum of 15 mg/m2/week) for at least eight weeks prior to the screening visit, and folic/folinic acid supplementation (according to standard medical practice of the center). Stable dose of no more than one NSAID for at least four weeks prior to the screening visit. Stable dose of oral prednisone (= 0.4 mg/kg/day or = 20 mg/day, whichever is lower) for at least one week prior to the screening visit. 7. Body weight of at least 12 kg. 8. Negative tuberculin skin test reaction (PPD 5 TU) (< 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines. Patients who have a positive PPD skin test with a documentation of BCG vaccination, who are at low environmental risk for tuberculosis infection or reactivation, and have a negative chest X-ray can be included A positive PPD sample will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group. - equal or greater than 15mm of induration for persons with no risk factors for TB -equal or greater than 10mm of induration for persons with increased probability of recent infection or with other clincal conditions that increased the risk for TB -equal or greater than 5mm of induration for vey high risk population (HIV), contact TB cases, immunosuppression (organ transplantation, steriods > 15mg/day of predisone for 1 month or more).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Use of : - Etanercept in the four weeks prior to the Baseline visit - Adalimumab in the eight weeks prior to the Baseline visit - Infliximab in the eight weeks prior to the Baseline visit - Any other investigational biologics in the eight weeks prior to the Baseline visit - Leflunomide in the four weeks prior to the Baseline visit. Documentation of a completion of a full cholestyramine elimination procedure after most recent leflunomide use will be required - Cyclosporine in the four weeks prior to the Baseline visit - Sulfasalazine or hydroxychloroquine in the eight weeks prior to the Baseline visit - i.v. immunoglobulin (i.v. Ig) in the eight weeks prior to the Baseline visit - 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, in the 24 weeks prior to the Baseline visit Wash out period may be longer according to local requirements. 2. History of recurrent bacterial, fungal or viral infection. 3. Evidence of currently active bacterial, fungal or viral infection. 4. Administration of live attenuated vaccine. 5. Uncontrolled severe systemic symptoms and/or biologic features of Macrophage Activation Syndrome (hemorrhages, central nervous system dysfunction, hepatomegaly, serum fibrinogen level < 2.5 g/L, cytopenia, hypertriglyceridemia, decreased platelet count, increased aspartate transaminase, hyperferritinemia). 6. Familial and social conditions rendering regular medical assessment not possible. 7. Participation in any clinical investigation within 4 weeks prior to dosing or loner if required by local regulations, and if for any other limitation of participation based on local regulations. 8. Donation or loss of blood (amount depending on age and weight, 10-20%, or more of volume, within 8 weeks prior to first dosing, or longer if required by local regulation. 9. Significant illness within two weeks prior to dosing 10. A past medical hsitory of clinically significant ECG abnormalilties or a family history grandparents, parents and siblings) of a prolonged QT-interval syndrome. 11. History of autonomic dysfunction (e.g. history of faiting, orthostatic hypotension, sinus arrthymia). 12. Uncontrolled hypertension 13. History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated). 14. History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug. 15. Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests at screening such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin (must not exceed twice the upper limit value of the normal range for age). 16. Presence of moderate to severe impaired renal function as indicated by clinically significantly abnormal creatinine or urea values or abnormal urinary constituents (e.g. albuminuria) at screening. Evidence of usrinary obstruction or difficulty in voiding at screening. 17. History of immunodeficiency diseases, including HIV (ELISA and \western blot) test results. 18. History of drug and alcohol abuse within 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.


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

Health Condition(s) or Problem(s) studied

Systemic Juvenile Idiopathic Arthritis (SJIA)
MedDRA version: 8.1 Level: PT Classification code 10059177 Term: Juvenile arthritis

Intervention(s)

Product Name: ACZ885
Product Code: ACZ885
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: ACZ885 Drug Substance
Current Sponsor code: ACZ885
Other descriptive name: ACZ885 Drug Substance
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: • To assess the proportion of patients with inactive disease at each dose level. • To investigate the possibility of corticosteroid tapering. • To establish a biomarker and pharmacogenomic characterization of these patients at baseline and to evaluate the treatment response to ACZ885.

Main Objective: • To evaluate the safety, tolerability and immunogenicity of sc administration of ACZ885 in pediatric subjects with active Systemic Juvenile Idiopathic Arthritis (SJIA). • To assess the initial efficacy profile (% responders to treatment and time to relapse) of sc dosing of ACZ885 in pediatric subjects with active SJIA according to the modified American College of Rheumatology (ACR) pediatric 30 definitions and the ability of ACZ885 to control the systemic manifestations of SJIA such as fever and rash. • To assess the PK of ACZ885 administered sc in children. • To assess PK and PD relationships in order to derive a dose and dosing regimen for Phase III (dose and dosing frequency required for relief of signs and symptoms and response according to at least ACR 30 definition).

Primary end point(s): To evaluate the safety, tolerability and immunogenicity of sc administration of ACZ885 in paediatric subjects with active Systemic Juvenile Idiopathic Arthritis (SJIA). To assess the initial efficacy profile (%responders to treatment and time relapse) of sc dosing of ACZ885 in paediatric subjects with active SJIA accordingly to the modified American College of Rheumatology (ACR) paediatric 30 definitions and the ability of the ACZ885 to control the systemic manifestations of SIJA such as fever and rash. To assess the PK of ACZ885 administered to children To assess PK and PD relaionships in order to derive a dose and dosing regimen for Phase III (dose and dosing frequency required for relief of signs and symptoms and response accordingly to at least ACR 30 definition)

Secondary ID(s)

not available

CACZ885A2203

2006-001834-42-FR

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 05/08/2015
• Date Completed: 09/03/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-001834-42/results