An open-label, long-term safety and efficacy study of ACZ885 (anti-interleukin-1ß monoclonal antibody) administered for at least 6 months in patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease - D2306

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2007-004367-22-GB
• Date of registration: 07/03/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label, long-term safety and efficacy study of ACZ885 (anti-interleukin-1ß monoclonal antibody) administered for at least 6 months in patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease - D2306
• Scientific title: An open-label, long-term safety and efficacy study of ACZ885 (anti-interleukin-1ß monoclonal antibody) administered for at least 6 months in patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease - D2306
• Date of first enrolment: 01/05/2008
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004367-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients at least 4 years of age at the time of the screening visit.
2. Patient’s informed consent for = 18 years of age before any assessment is
performed.
3. Parent or legal guardian’s written informed consent and child’s assent, if
appropriate, are required before any assessment is performed for patients
<18 years of age.
4. Patients with a diagnosis of FCAS, MWS, or
NOMID.
At study entry, new ACZ885 NAIVE patients should have symptoms requiring pharmacological intervention.
At the time of screening, patients can be either untreated or treated (i.e. under
ACZ885, anakinra, or any other investigational IL-1 blocking therapy). Prior
agreement between the Investigator and Novartis for study eligibility is required
for patients who do not have a molecular diagnosis of NALP3 mutations available
(EITHER TESTING NOT PERFORMED, OR TESTING PERFORMED BUT NEGATIVE) upon study entry. FOR THOSE PATIENTS WHO HAVE NOT BEEN MOLECULLARLY TESTED FOR NALP3 MUTATIONS, MOLECULAR TESTING SHOULD BE PERFORMED DURING THE COURSE OF THE STUDY.)
5. For patients under anakinra therapy or any other investigational IL-1 blocking
therapy, these treatments should be discontinued prior to the baseline visit (see
Section 6.5.8 for specific time points for discontinuing treatments prior to the
baseline visit).
6. Patients from the A2102 study may enter this study upon signing informed
consent irrespective of whether they are in remission or flaring. However, dosing
at Visit 2 (Baseline Visit) can only occur if either 1) the patient is experiencing
disease flare or 2) at least two months have elapsed from their last injection even
in the absence of flare, whichever is earlier.
7. Patients who completed the D2304 study may enter this study upon signing
informed consent. A patient is defined as completing the study if he/she
completed the D2304 study up to and including Visit 15 (End of Study Visit).
8. PATIENTS WHO COMPLETED THE DD201 STUDY MAY ENTER THIS STUDY UPON SIGNING INFORMED CONSENT. A PATIENT IS DEFINED AS COMPLETING THE STUDY IF HE/SHE COMPLETED THE D2201 STUDY UP TO AN INCLUDING THE END OF STUDY VISIT.
9. Patients who discontinued from the A2102, D2201 or D2304 studies and for whom in the
Investigator’s judgment (with prior agreement from Novartis) treatment with
ACZ885 in this study is considered appropriate.
10. Body weight = 15 kg.
11. Able to communicate with the investigator and comply with the requirements of
the study (for children the parent can assist when necessary).
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or nursing (lactating) women.
2. Women of child-bearing potential unless they meet the following definition of postmenopausal state: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or are using one or more of the acceptable methods of contraception detailed in the protocol are used.
3. Participation in any clinical investigation within 4 weeks prior to dosing or longer if
required by local regulation with the exception of trials with anakinra, other
investigational IL-1 blocking therapies, and/or ACZ885.
4. History of being immunocompromised, including a positive HIV at screening
(ELISA and Western blot) test result.
5. A positive HBsAg or Hepatitis C antibody test result.
6. Live vaccinations within 3 months prior to the start of the trial, during the trial, and
up to 3 months following the last dose.
7. History of drug or alcohol abuse within the 12 months prior to dosing.
8. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing for
adults (For children the cut-off amount of donation or loss of blood should be
based on the Investigator's judgment & according to the local regulations. Please
also refer to Appendix 4 for the recommended sample volume per blood draw for
children).
9. History of significant medical conditions, which in the Investigator’s opinion would
exclude the patient from participating in this trial (this can be discussed with
Novartis on a case by case basis in case of uncertainty).
10. History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
11. Positive tuberculin skin test reaction (PPD 5 tuberculin units or as according to
local standard practice) (= 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 (TB) infection or reactivation, and have a negative chest X-ray can be
included. A positive PPD test has been defined using the [MMWR 2000
guidance], summarized as criteria for tuberculin positivity by risk group:
• equal or greater than 15 mm of induration for persons with no risk factors for
TB
• equal or greater than 10 mm of induration for persons with an increased
probability of recent infection or with other clinical conditions that increased
the risk for TB
• equal or greater than 5 mm of induration for very high risk population (HIV),
contact TB cases, immunosuppression (organ transplantation, steroids
> 15 mg/day of prednisone for 1 month or more).
12.Precaution against tuberculosis should be handled according to the best medical
practice consistent to the local standards in each country with prior consultation
with Novartis. Patients requi

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

Health Condition(s) or Problem(s) studied

The following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
MedDRA version: 9.1 Level: LLT Classification code 10064569 Term: Muckle-Wells syndrome

Intervention(s)

Product Name: ACZ885
Product Code: ACZ885
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Canakinumab (WHO approval pending)
CAS Number: -
Current Sponsor code: ACZ885
Other descriptive name: Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150 mg-

Primary Outcome(s)

Secondary Objective: 1. Maintenance of response over time defined by the number of patients who do not relapse as determined by the Physician’s global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers.
2. to Assess number of patients who require a dose adjustment or an administration frequency adjustment, with subsequent maintenance of response over time as determined by the Physician’s global assessment of autoinflammatory disease activity, assessment of skin disease and CRP and/or SAA.
3. Immunogenicity of ACZ885. PK of ACZ885, in particular, comparison of the new HSA- (human serum albumin) drug formulation with previously used HSA+ formulation.
4. Long-term effects of ACZ885 on disease progression with regards to deafness, kidney function, neurological and ophthalmological symptoms.
5. Long term maintenance of Health-Related Quality of Life
(HRQoL) of ACZ885 by using the HAQ©, SF-36®, FACIT-Fatigue©, and CHQ-PF28©.

Main Objective: Long-term safety and tolerability of ACZ885 in patients who participated in the A2102, D2201 or D2304 studies or in newly identified patients with the following cryopyrin-associated periodic syndromes (CAPS): Familial Cold Autoinflammatory Syndrome FCAS), Muckle-Wells Syndrome (MWS) or Neonatal Onset Multisystem Inflammatory Disease (NOMID).

Primary end point(s): Assess Long term safety and tolerability

Secondary ID(s)

CACZ885D2306

Not available

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 12/08/2015
• Date Completed: 29/04/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004367-22/results