?A study to check how beneficial and safe the drug canakinumab is for patients with TNF-receptor associated periodic syndrome (TRAPS)

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2010-020061-24-IE
• Date of registration: 18/05/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: ?A study to check how beneficial and safe the drug canakinumab is for patients with TNF-receptor associated periodic syndrome (TRAPS)
• Scientific title: An open-label, multicenter, efficacy and safety study of 4-month canakinumab treatment with 5-month follow-up and long-term treatment period in patients with active recurrent or chronic TNF-receptor associated periodic syndrome (TRAPS) - D2203
• Date of first enrolment: 24/08/2010
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020061-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Ireland, Italy, United Kingdom

Contacts

• Name: Chief Scientific Officer
• Affiliation: Novartis Ireland

• Name: Chief Scientific Officer
• Affiliation: Novartis Ireland

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient’s written informed consent for = 18 years of age before any assessment is performed. 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.
2. Male and female patients at least 4 years of age at the time of the screening visit.
3. Patients with a clinical diagnosis of TRAPS and a mutation of TNFRSF1A gene. Patients with low penetrance mutations, such as R92Q or P46L, can be included with mutual agreement between the investigator and Novartis.
4. Patients with a diagnosis of recurrent TRAPS must experience more than 6 episodes/year prior to receiving an effective biologic therapy and the duration of each episode lasted at least 8 days. For patients receiving biologic therapy, this criterion applies to prior to receiving the biologic therapy.
5. Patients who have been treated with anakinra must have demonstrated a partial or complete clinical response with an associated decrease in their inflammation markers (CRP and SAA).
6. Active TRAPS as evidenced by clinical signs and symptoms of active TRAPS (Physician’s Global Assessment = 2) and an elevated CRP > 10mg/L (Normal CRP range = 10 mg/L) and/or SAA > 10 mg/L (Normal SAA range = 10 mg/L) at time of first canakinumab treatment.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
2. Women of child-bearing potential, defined as pre-menarche females aged 8 years and above or all women physiologically capable of becoming pregnant, UNLESS they are
• women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
• women whose partners have been sterilized by vasectomy or other means
• using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices [IUDs]; periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] is not acceptable) or total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance.
• Women of child-bearing potential should be willing to use a reliable contraception
throughout the study and for 3 months after study drug discontinuation.
• Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
3. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
4. Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (= 5 mm induration) at screening or within 2 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (= 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test.
5. Live vaccinations within 3 months prior to the start of the trial, during the trial, and up months following the last dose.
6. History of significant other medical conditions, which in the Investigator’s opinion would exclude the patient from participating in this trial.
7. History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s).
8. Use of the following therapies:
a. Corticosteroids (oral prednisone (or equivalent)) > 0.2 mg/kg/day (or greater than the maximum of 15 mg/day for children over 60 kg) within 1 week prior to the Baseline visit
b. Anakinra within 24 hours prior to Baseline visit
c. Canakinumab within 3 months prior to Baseline visit
d. Rilonacept within 1 week prior to Baseline visit
e. Tocilizumab within 3 weeks prior to Baseline visit
f. Etanercept within 4 weeks prior to Baseline visit
g. Rituximab within 26 weeks prior to the Baseline visit
h. Leflunomide within 4 weeks prior to the Baseline visit. Documentation of a completion of a full cholestyramine elimination treatment after most recent leflunomide use will be required.
i. Thalidomide within 4 weeks prior to the Baseline visit
j. Cyclosporine within 4 weeks prior t

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

Health Condition(s) or Problem(s) studied

TNF-receptor associated periodic syndrome (TRAPS)
MedDRA version: 14.1 Level: LLT Classification code 10067783 Term: Tumor necrosis factor receptor-associated periodic syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

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
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-

Primary Outcome(s)

Main Objective: To assess if canakinumab induces complete or almost complete response in patients with active TRAPS at Day 15 (defined as 15 days after the first dose).

Secondary Objective: 1. To assess if canakinumab can induce complete or almost complete response in patients with active TRAPS at Day 8.
2. To assess the percentage of patients with complete clinical remission (Physician’s Global Assessment score = 1) at Day 8 and Day 15.
3. To assess the percentage of patients with C-reactive protein (CRP) < 10mg/L and serum amyloid A (SAA) < 10mg/L at Day 8 and Day 15.
4. To assess if canakinumab can induce complete or almost complete response at Day 15 for patients who received an additional dose on Day 8.
5. To assess time to patient’s assessed clinical remission (Patient’s Global Assessment score =1) after initial canakinumab treatment.
6. To assess time to physician’s assessed clinical remission (Physician’s Global Assessment score = 1) after initial canakinumab treatment.
7. To assess the profile over time in CRP and SAA from baseline to end of study.

Primary end point(s): To assess if canakinumab induces complete or almost complete response active TRAPS at Day 15 (defined as 15 days after the first dose).

Timepoint(s) of evaluation of this end point: At Day 15

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 8 & Day 15/ 4-month and long-term treatment period

Secondary end point(s): Percentage of patients with complete clinical remission as measured by The Physician's Global Assessment score

Percentage of patients with C-reactive protein (CRP) < 10mg/L and serum amyloid A (SAA) < 10mg/L

Complete or almost complete response (defined by the Physician's Global Assessment, C-reactive protein [CRP])

Secondary ID(s)

CACZ885D2203

Source(s) of Monetary Support

Novartis Pharma Services