Clinical Trials Register

Summary
EudraCT Number:	2010-020061-24
Sponsor's Protocol Code Number:	CACZ885D2203
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-05-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2010-020061-24

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

D2203

A.4.1

Sponsor's protocol code number

CACZ885D2203

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Ireland
B.5.2	Functional name of contact point	Chief Scientific Officer
B.5.3	Address:
B.5.3.1	Street Address	Beech Hill Office Campus, Clonskeagh
B.5.3.2	Town/ city	Dublin
B.5.3.3	Post code	4
B.5.3.4	Country	Ireland
B.5.4	Telephone number	35312601255
B.5.5	Fax number	35312601263
B.5.6	E-mail	greg.hays@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ILARIS
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	canakinumab
D.3.2	Product code	ACZ885
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CANAKINUMAB
D.3.9.1	CAS number	914613-48-2
D.3.9.2	Current sponsor code	ACZ885
D.3.9.3	Other descriptive name	Recombinant human monoclonal antibody to human IL-1Beta of the IgG1/K class
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

TNF-receptor associated periodic syndrome (TRAPS)

E.1.1.1

Medical condition in easily understood language

TRAPS is a disease characterized by recurrent attacks of fever associated with rashes, abdominal and/or arm/leg pain, and swelling around the eyes

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10067783
E.1.2	Term	Tumor necrosis factor receptor-associated periodic syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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).

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 to the Baseline visit
k. Intravenous immunoglobulin (i.v. Ig) within 8 weeks prior to the Baseline visit
l. 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil within 12 weeks prior to the Baseline visit
m. Intra-articular, peri-articular or intramuscular corticosteroid injections within 4 weeks prior to the Baseline visit
n. Any other investigational biologics within 8 weeks prior to the Baseline visit
o. Any other investigational drugs, other than investigational biologic treatment, within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer
9. History of known hypersensitivity to canakinumab.
10. 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

E.5 End points

E.5.1

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).

E.5.1.1

Timepoint(s) of evaluation of this end point

At Day 15

E.5.2

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])

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 8 & Day 15/ 4-month and long-term treatment period

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised