E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Muckle-Wells Syndrome (Autoinflammatory Disease) |
|
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. |
|
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 |
|
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 will investigate the clinical efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of
ACZ885, administered intravenously and subcutaneously to patients with NALP3 mutations whose clinical symptoms are either untreated or insufficiently treated and require medical intervention. |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients aged 4 to 75 years (inclusive)
•Body weight ≥ 12 kg and < 100 kg.
Females of child-bearing potential must have a negative pregnancy test. Additional birth control details to be provided at screening.
•Documented molecular diagnosis of NALP3 mutations and clinical symptoms that are either untreated or insufficiently treated and require medical intervention.
•Patients under anakinra therapy or any other IL-1 blocking therapy, whose clinical symptoms improved under treatment and are willing to discontinue that therapy until a relapse becomes
evident.
•Patients with a very severe characteristics requiring oral prednisone are eligible if the dose is stable (≤ 0.4 mg/kg/day or ≤ 20 mg/day, whichever is lower) for at least 1 week prior to the
screening visit. Steroid therapy may be tapered during treatment with ACZ885 at the discretion of the investigator.
•Parents' or legal guardian's written informed consent (patient's informed consent for ≥ 18 years of age) and child's assent, if appropriate, are required prior to study participation.
Other protocol-defined inclusion criteria may apply. |
|
E.4 | Principal exclusion criteria |
•Participation in any clinical trial investigation (except trials with anakinra) within 4 weeks prior to dosing or longer per local regulation
•Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. Therapeutic antibodies (e.g. anti-TNF-alpha antibodies) must be discontinued at least 60 days before dosing.
•Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing. A past personal or close family medical history of clinically significant ECG abnormalities or prolonged QT-interval syndrome.
•History of
◦Immunocompromise, including a positive HIV result.
◦Positive Hepatitis B surface antigen or Hepatitis C test result.
◦Drug or alcohol abuse within the 12 months prior to dosing.
◦Tuberculosis.
◦Renal transplant.
◦Evidence of lymphoma.
•Active medical condition preventing participation in the study such as infection, poorly controlled diabetes etc.
•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.
Other protocol-defined exclusion criteria may apply. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Response to treatment and time to relapse after ACZ885 administration according to monthly investigator's clinical assessments, laboratory monitoring, and patient diaries. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Assessment of safety,tolerability and immunogenicity of ACZ885 at each clinical visit.
Evaluation of ACZ885 PK and PD at each clinical visit Evaluate efficacy towards hearing loss (every 4 months), kidney function (every 4 months), neurological symptoms |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every month unless every 4 months indicated above |
|
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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 |
|
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.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |