E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF) |
|
E.1.1.1 | Medical condition in easily understood language |
rare orphan diseases as part of an expanding group of auto inflammatory
disorders with recurrent episodes of systemic inflammation of target
organs and body systems |
|
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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016207 |
E.1.2 | Term | Familial mediterranean fever |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072010 |
E.1.2 | Term | Hyper IgD syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
|
|
E.2.2 | Secondary objectives of the trial |
• 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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | 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. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
16 weeks (end of Epoch 2) |
|
E.5.2 | Secondary end point(s) |
Percentage of participants who achieve Physician's global assessment < 2
Percentage of participants with the serologic remission |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
16 weeks (end of Epoch 2) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Netherlands |
Russian Federation |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |