E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muckle-Wells Syndrome (Autoinflammatory Disease) |
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E.1.1.1 | Medical condition in easily understood language |
Muckle Wells Syndrome is an inflammatory disorder caused by the body making too much of a protein called interleukin 1β (IL-1β). Symptoms include redness, swelling, pain, fever and loss of hearing. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064569 |
E.1.2 | Term | Muckle-Wells syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.
Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.
Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.
Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
•Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study will have the option to participate in this study upon disease flare
•Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).
Other protocol-defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
•History of being immunocompromised, including a positive HIV at screening test result.
•No live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
•History of significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
•History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
•Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
2. Number of Participants Who Experienced a Disease Flare in Part II |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
32 weeks after study start |
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E.5.2 | Secondary end point(s) |
1. Number of Participants With Treatment Response in Part I (After 8 Weeks)
2. Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part)
3. Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8.
4. Pharmacokinetics (CLD (L/d))
5. Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
6. Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
7. Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 8 weeks after study start
2. 32 weeks after study start
3. Week 8 and Week 32
4. 48 weeks after study start
5. until Week 8
6. 32 weeks after study start
7. 48 weeks after study start |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity assessment |
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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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Randomised withdrawal design. Double blind in Part II. |
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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.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |