E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe plaque psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
E.1.2 | System Organ Class | 100000004858 |
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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 |
To compare the efficacy of subcutaneous injections of brodalumab to oral administration of fumaric acid esters in subjects with moderate to severe plaque psoriasis who are naive to systemic
treatment. |
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E.2.2 | Secondary objectives of the trial |
- To compare the effect on patient reported outcomes of subcutaneous injections of brodalumab to oral administration of fumaric acid esters in subjects with moderate to severe plaque
psoriasis.
- To evaluate the safety and tolerability of subcutaneous injections of brodalumab versus oral administration of fumaric acid esters in subjects with moderate to severe plaque psoriasis. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men or women ≥18 years of age at the time of screening
- Subjects with chronic plaque type psoriasis diagnosed for at least 6 months before randomisation
- Subjects with moderate to severe plaque psoriasis in whom topical therapy is not adequate and who are candidates for systemic therapy, defined at randomisation by PASI >10, affected BSA >10% and DLQI >10
- Subject has no known history of active tuberculosis
- Subject has a negative test for tuberculosis taken at screening (negative QuantiFERON test)
- Subject and/or subject’s designee is/are capable of administering subcutaneous injections |
|
E.4 | Principal exclusion criteria |
• Previous or current systemic treatment of plaque psoriasis or known contraindication for systemic therapy.
• Previous or current PUVA (psoralens and ultraviolet A) therapy.
• Washouts and non-permitted drugs:
a) Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline
b) Have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids).
c) Have received any biologic immune modulating treatment used for indication other than psoriasis within 4 weeks of baseline or within a period of 5 half-lifes of the received treatment,
whichever is longer
d) Have received any other systemic immune modulating treatment (including but not limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or parenteral corticosteroids etc. used
for indication other than psoriasis) within 4 weeks of baseline or within a period of 5 half-lifes of the received treatment, whichever is longer.
• Subjects with any of the following laboratory abnormalities at screening:
a) Leukocyte cell count below 3×109/L or lymphocyte count below 0.7×109/L.
b) Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2× ULN (upper level of normal limit).
c) Absolute neutrophil count < 2× 109/L.
d) Serum creatinine > ULN.
• History of depressive disorder within the last 2 years including current anti-depressive treatment.
• Any positive finding in history of suicidal behaviour (e.g., ‘actual suicide attempts’, ‘interrupted attempts’, ‘aborted attempts’, or ‘preparatory actions’) based on the eC-SSRS questionnaire at screening or baseline.
• Any positive finding in suicidal ideation of level 4 or 5 (‘some intent to act, no plan’ or ‘specific plan and intent’) based on the eC-SSRS questionnaire at screening or baseline.
• A PHQ-8 score of ≥10 corresponding to moderate to severe depression at screening or baseline. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- At least 75% improvement from baseline at Week 24 in Psoriasis Area and Severity Index (PASI)
- Static Physician’s Global Assessment (sPGA) scale score of 0 or 1 |
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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) |
- At least 90% improvement from baseline at Week 24 in PASI
- 100% improvement from baseline at Week 24 in PASI
- Change from baseline at Week 24 in PASI score
- PASI improvement (%) from baseline at Week 24
- Change from baseline at Week 24 in affected body surface area (BSA)
- Burden of symptoms assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 30 |
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
|
A subject is considered to have completed the trial if they have completed all periods of the trial, including the follow-up visit scheduled at Week 32 for brodalumab and at Week 26 for fumaric acid esters. The End of Trial Form must be completed for all randomised subjects. The end of the trial is defined as the date of the last visit of the last subject in the trial. |
|
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 | |
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 |