E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
active chronic plaque-type psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
active chronic plaque-type psoriasis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
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 |
To evaluate flow mediated dilation (FMD) by Doppler ultrasound at week 12 in subjects in treatment arm A (300 mg Secukinumab) compared to the pooled group of patients in treatment arms C and D (placebo up to week 12). |
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E.2.2 | Secondary objectives of the trial |
Cardiovascular Surrogate Markers:
To evaluate flow mediated dilation by Doppler Ultrasound at weeks 4, 12, 24 and 52
To evaluate arterial stiffness by pulse wave analysis and pulse wave velocity at weeks 4, 12, 24 and 52
To evaluate soluble biomarkers from blood at weeks 4, 12, 24 and 52
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MRI sub-study
objectives:
To evaluate total plaque burden in the carotid artery and aorta as well as plaque composition in the carotid artery when measured in a complex plaque by 3.0 Tesla MRI at weeks 12 and 52 in a sub-study (40 patients)
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E.3 | Principal inclusion criteria |
1. Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed.
2. Men or women at least 18 years of age at time of screening.
3. Chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization with a PASI score ≥ 10 at randomization.
4. Inadequate response, intolerance or contraindication to first-line conventional systemic psoriasis treatments as documented in the patient’s medical history or reported by the patient or determined by the investigator at screening. Relative contraindications such as interference of patient’s lifestyle with the treatment are accepted.
5. At least one of the following to exclude chest infection and malignancy before initiation of a biologic immunomodulating therapy in accordance with current clinical guidelines:
o Imaging of the chest (X-ray, computerized tomography (CT), or MRI) obtained within 12 weeks prior to screening, and evaluated by a qualified physician.
o MRI of the chest obtained at screening and evaluated by a qualified physician.
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E.4 | Principal exclusion criteria |
1. Patients incapable of giving full informed consent.
2. Forms of psoriasis other than chronic plaque-type at screening or randomization.
3. Drug-induced psoriasis at randomization.
4. Ongoing use of prohibited psoriasis and non-psoriasis treatments. Washout periods have to be adhered to.
5. Use of other investigational drugs at the time of enrollment, or within 30 days or 10 half-lives of enrollment, whichever is longer.
6. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A or the IL-17A receptor.
7. Women
a. who are pregnant or breast feeding
b. who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception (Pearl Index <1) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women is required with sufficient lead time before inclusion.
8. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy. Patients with psoriatic arthritis are not excluded.
9. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
10. Known severe cardiovascular disease including but not limited to
a. congestive heart failure with ejection fraction <50% and NYHA class II-IV.
b. grade II or higher valvular disease.
c. coronary artery disease requiring reperfusion during the study period.
d. uncontrolled hypertension (repeated values of systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite maximally tolerated therapy). Patients who are at the time of screeningnot treated with maximal tolerated therapy may be rescreened after therapy has been successfully adjusted and well tolerated for at least 4 weeks.
e. documented coronary heart disease in the medical history.
f. symptoms or findings compatible with the presence of coronary artery disesase.
11. Inability to suspend therapy with angiotensin-converting-enzyme inhibitors, nitrates, calcium channel inhibitors, and angiotensin-receptor blockers for at least 12 hours before visits.
12. Subjects with a serum creatinine level exceeding 2.0 mg/dl at screening.
13. Screening total white blood cell count <2,500/μl, or platelets <100,000/μl or neutrophils <1,500/μl or hemoglobin <8.5 g/dl.
14. Chest X-ray, CT, or MRI with evidence of ongoing infectious or malignant process, obtained within 12 weeks prior to screening or after screening and prior to randomization, and evaluated by a qualified physician.
15. Active systemic infections during the last two weeks prior to randomization or any infection that reoccurs on a regular basis.
16. History of an ongoing, chronic or recurrent infectious disease including recurrent respiratory and/or urinary tract infections or evidence of tuberculosis infection.
17. Past medical history record of infection with HIV, hepatitis B or hepatitis C prior to randomization.
18. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
19. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
20. Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the subject unsuitable for the trial or puts the subject at increased risk.
21. Patients, who have already been randomized into this trial earlier must not be included a second time.
22. Study personnel or first degree relatives of investigator(s) must not be included in the study.
23. Inability or unwillingness to undergo repeated venipuncture
24. Subjects not willing to limit UV light exposure during the course of the study
25. Any medical or psychiatric condition which, in the investigator’s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
26. History or evidence of ongoing alcohol or drug abuse, within the last six months before randomization.
27. Plans for administration of live vaccines during the study period or 6 weeks prior to randomization.
28. Upper thigh circumference >102 cm and/or upper arm circumference >49 cm.
29. Current or medical history of diverticulitis and/or colitis.
30. For the MRI sub-study, patients unwilling to undergo MRI assessment or with contraindications to MRI.
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of flow mediated dilation by Doppler ultrasound in subjects in treatment arm A (300 mg Secukinumab) compared to the pooled group of patients in treatment arms C and D (placebo up to week 12). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Cardiovascular Surrogate Markers:
To evaluate flow mediated dilation by Doppler Ultrasound
To evaluate arterial stiffness by pulse wave analysis and pulse wave velocity
To evaluate soluble biomarkers from blood
To evaluate total plaque burden in the carotid artery and aorta as well as plaque composition in the carotid artery when measured in a complex plaque by 3.0 Tesla MRI in a sub-study (40 patients)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cardiovascular Surrogate Markers:
Doppler Ultrasound at weeks 4, 12, 24 and 52
pulse wave analysis and pulse wave velocity at weeks 4, 12, 24 and 52
Evaluation of soluble biomarkers from blood at weeks 4, 12, 24 and 52
3.0 Tesla MRI at weeks 12 and 52 in a sub-study
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
exploratory biomarker study |
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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 | 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 | 4 |
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 | 23 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |