Study of efficacy and safety of canakinumab in patients with Hereditary Periodic Fevers

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2013-004291-35-BE
• Date of registration: 27/05/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and safety of canakinumab in patients with Hereditary Periodic Fevers
• Scientific title: A randomized, double-blind, placebo controlled study of canakinumab in patients with Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), with subsequent randomized withdrawal/ dosing frequency reduction and open-label long term treatment epochs
• Date of first enrolment: 20/06/2014
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004291-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• 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, Canada, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Netherlands, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Patient's written informed consent (or parent's written informed
consent in case of pediatric patient) at screening
• Male and female patients at least 2 years of age at the time of the
screening visit. Male and female patients >28 days but <2 years old at
the time of the screening visit will be enrolled in the open label arm only.
• Confirmed diagnosis at screening
• Active flare and CRP >10mg/L at randomization
Are the trial subjects under 18? yes
Number of subjects for this age range: 105
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Use of the following therapies (within varying protocol defined
timeframes): Corticosteroids, anakinra, canakinumab, rilonacept,
tocilizumab, TNF inhibitors, abatacept, tofacitinib, rituximab,
leflunomide, thalidomide, cyclosporine, intravenous immunoglobulin, 6-
Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, any
other investigational biologics
- History of malignancy of any organ system (other than localized basal
cell carcinoma of the skin or in - situ cervical cancer), treated or
untreated
- Significant medical diseases, including but not limited to the following:
a. History of organ transplantation
b. Elevated alanine aminotransferase (ALT) =3x ULN
c. Elevated aspartate aminotransferase (AST) =3x ULN
d. Increase in total bilirubin
e. Serious hepatic disorder (Child-Pugh scores B or C)
f. Chronic Kidney Disease
g. Thyroid disease
h. Diagnosis of active peptic ulcer disease
i. Coagulopathy j. Significant CNS effects including vertigo and dizziness
j. Any conditions or significant medical problems which
immunecompromise the patient and/or places the patient at
unacceptable risk for immunomodulatory therapy
- Live vaccinations within 3 months prior to the start of the trial, during
the trial, and up to 3 months following the last dose


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

Health Condition(s) or Problem(s) studied

Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF)
MedDRA version: 18.0 Level: PT Classification code 10016207 Term: Familial mediterranean fever System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 18.0 Level: LLT Classification code 10067783 Term: Tumor necrosis factor receptor-associated periodic syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 18.0 Level: PT Classification code 10072010 Term: Hyper IgD syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

Product Name: canakinumab
Product Code: ACZ885
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Proportion of participants with resolution of the index flare at Day 15
and no new disease flares over 16 weeks following randomization.
To demonstrate clinically meaningful reduction of disease activity with
canakinumab versus placebo.

Main Objective: The primary objective of the randomized treatment epoch and for the overall
study is to demonstrate that subcutaneous canakinumab administered every 4 weeks is superior to placebo in achieving a clinically meaningful reduction of disease activity defined as resolution of the index flare at Day 15 and no new disease flares over 16 weeks of treatment.

Secondary Objective: • To evaluate the percentage of patients who achieve a Physician Global Assessment of Disease Activity (PGA) <2 (“minimal” or “none”) at Week 16
• To evaluate the percentage of patients with the serologic remission at Week 16 (defined as C-reactive protein [CRP] < or = 10 mg/L)
• To evaluate the percentage of patients with normalized Serum Amyloid A (SAA) level at Week 16 (defined as SAA < or = 10 mg/L)
• To evaluate the percentage of canakinumab responders in Epoch 2 who maintain a clinically meaningful response (absence of new flares) when switched to canakinumab every 8 weeks compared to placebo (Epoch 3)
• To evaluate the long-term safety and tolerability and immunogenicity of canakinumab
• To evaluate the pharmacokinetics/ pharmacodynamics of canakinumab

Timepoint(s) of evaluation of this end point: 16 weeks (end of Epoch 2)

Secondary Outcome(s)

Secondary end point(s): Percentage of participants who achieve Physician's global assessment < 2
Percentage of participants with the serologic remission

Timepoint(s) of evaluation of this end point: 16 weeks (end of Epoch 2)

Secondary ID(s)

2013-004291-35-IT

CACZ885N2301

NCT02059291

Source(s) of Monetary Support

Novartis Pharma Services AG