E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Plaque psoriasis diagnosed for at least 12 months with or without psoriatic arthritis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
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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 |
Efficacy (as assessed by PASI response) of AEB071 in patients with moderate to severe plaque psoriasis as a function of treatment dose and treatment duration. |
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E.2.2 | Secondary objectives of the trial |
(1) to evaluate overall safety of AEB071 in the Treatment Period and Follow-up Periods as assessed by ECG and laboratory parameters, rates of AEs, and percentage of patients requiring interruption or discontinuation of study drug due to AEs; (2) to evaluate the efficacy of AEB071 compared with placebo within the Treatment Period as measured by PASI, and Investigator’s Global Assessment (IGA) of psoriasis; and (3) to evaluate the effect of treatment withdrawal and disease recurrence in the treatment-free Follow-up Period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women, between 18 and 75 years of age, inclusive at time of consent. 2. Moderate to severe plaque psoriasis diagnosed for at least 12 months (with or without presence of psoriatic arthritis as a comorbidity) requiring systemic therapy 3. Severity of disease meeting ALL of the following three criteria: - Psoriasis Area and Severity Index (PASI) score of 10 or greater - Total Body Surface Area (BSA) of 10% or greater affected by plaque psoriasis - Investigator’s Global Assessment (IGA) score of 3 or greater 4. Patients must be able to communicate with the investigator and comply with the requirements of the study and must give written informed consent before any asessment is performed. |
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E.4 | Principal exclusion criteria |
1. Hematological abnormalities i.e., leucocytes (total WBC) < 4.000/mm3, neutrophils/granulocytes (ANC/AGC) < 1.500/mm3, lymphocytes < 1000/mm3, platelets < 100.000/mm3, hemoglobin < 10 g/dL at screening 2. Heart rate < 50 or > 90 bpm when resting for 5 mins 3. Family history of long QT syndrome, or QTcF > 470 msec at baseline 4. History of tachyarrhythmia as defined by protocol. 5. History of conduction abnormality as defined by protocol. 6. Uncontrolled or unstable angina pectoris; history of myocardial infarction within previous 12 mths 7. Known history of congestive heart failure or known LVEF < 45% 8. History of percutaneous coronary intervention (PCI) or cardiac ablation 9. History of syncope 10. History of stroke or transient ischemic attack (TIA) 11. Implanted cardiac pacemaker or defibrillator 12. History of major gastrointestinal surgery 13. Evidence of being PPD+ with confirmatory chest X-ray indicating active/inactive tuberculosis at screening 14. Serum potassium level outside normal range 15. Known to be immunocompromised or positive HIV test result at screening 16. Positive hepatitis B or hepatitis C test result at screening 17. Abnormalities in liver function tests as defined in protocol. 18. Active systemic infections within the past 2 weeks other than common cold 19. History of malignancy of any organ system, treated or untreated, whether or not there is evidence of local recurrence or metastases 20. Current guttate, generalized erythrodermic, or pustular psoriasis (symptoms of inverse psoriasis are allowed as long as plaque psoriasis is predominant) 21. Current drug associated psoriasis as defined in the protocol. 22. History of drug or alcohol abuse within the 12 months prior to screening 23. Hypersensitivity to AEB071 or any ingredient of study drug 24. Any significant medical condition the severity of which prevents the patient from participating in this study according to investigators assessment 25. Use or planned use of prohibited treatments/medications within the period specified in protocol 26. Body weight below 45 kg 27. Donation or loss of 400 ml or more blood within 8 weeks prior to first dosing 28. 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 (>5 mIU/mL) 29. Women of childbearing potential (including women who have had a bilateral tubal ligation) unless they are using highly effective methods of contraception.
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E.5 End points |
E.5.1 | Primary end point(s) |
- The primary efficacy variable will be Treatment response defined as achieving PASI 75. - Secondary efficacy variables will be overall change in PASI score during the Treatment Period and treatment success in the Treatment Period based on IGA score. - Exploratory efficacy variables will be PASI, IGA, PASI 50, PASI 75 and PASI 90 at each visit, time to rebound, time to relapse, duration of remission, duration of treatment response, finger nail changes, markers of systemic inflammation (levels of C-reactive protein [CRP]); and patient’s assessments of: psoriasis, pruritus, psoriatic arthritis, psoriasis specific Quality of Life (PSORIQoL), functional disability (DLQI); and the generic health status (SF-36) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 17 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 27 |