E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adult subjects with moderate-to-severe plaque psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
adults with moderate-to-severe psoriasis |
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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 | 10071117 |
E.1.2 | Term | Plaque psoriasis |
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 brodalumab with guselkumab in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of brodalumab compared with guselkumab while ontreatment for up to 28 weeks in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.
To evaluate the efficacy of brodalumab compared with guselkumab through Week 28 in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.
To evaluate the safety of brodalumab compared with guselkumab throughout the trial (28 weeks) in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is ≥18 years of age at the time of screening.
- Subject has a diagnosis of plaque psoriasis for at least 6 months before the first administration of investigational medicinal product (IMP) as determined by the investigator.
- Subject has inadequately controlled plaque psoriasis currently treated with ustekinumab, and fulfil ALL of the following criteria:
- Ustekinumab administered at least 3 times at or higher than the
approved dose or frequency for at least 24 weeks.
- IGA ≥2 at screening and baseline.
- Absolute PASI >3 at screening and baseline.
- The last administration of ustekinumab was ≥12 weeks before randomisation.
- Subject has no active tuberculosis at screening (negative QuantiFERON® or purified protein derivative [PPD] test). Subjects
with adequately treated latent tuberculosis are eligible. |
|
E.4 | Principal exclusion criteria |
- Subject was diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g. eczema) that would interfere with evaluations of the effect of IMP on plaque psoriasis.
- Subject has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus).
- Subject has any systemic disease (e.g. renal failure, heart failure, hypertension, liver disease, diabetes, anaemia) considered by the investigator to be clinically significant and uncontrolled.
- Subject has a known history of Crohn’s disease.
- Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
- Subject has a history of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
- Subject has a known history of active tuberculosis.
- Subject has a history of suicidal behaviour (i.e. ‘actual suicide attempt’, ‘interrupted attempt’, ‘aborted attempt’, or ‘preparatory acts or behaviour’) based on the Columbia-Suicide Severity Rating Scale (CSSRS) questionnaire at screening or baseline.
- Subject has any suicidal ideation of severity 4 or 5 (‘some intent to act, no plan’ or ‘specific plan and intent’) based on the C-SSRS questionnaire at screening or baseline.
- Subject has a Patient Health Questionnaire-8 (PHQ-8) score of ≥10, corresponding to moderate-to-severe depression at screening or baseline.
- Subject has previously received more than 1 tumour necrosis factor-α (TNF-α) inhibitor.
- Subject has previously been treated with any anti-interleukin (IL)-17A, anti-IL-17 receptor subunit A, or anti-IL-23 besides ustekinumab.
- Subject has known or suspected hypersensitivity to any component(s) of the IMPs. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
Having PASI 100 response at Week 16.
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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) |
Key secondary endpoint:
Time to PASI 100 response
Secondary endpoints:
Time to PASI 90 response
Having PASI 100 response, assessed separately at Weeks 4, 8, and 28.
Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28.
Having IGA of 0, assessed separately at Week 16 and Week 28.
Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.
Having DLQI total score of 0 or 1, assessed separately at Weeks 4, 8, 12, 16, 20, 24, and 28.
Change in SF-36v24 score from baseline, assessed separately at Weeks 4, 8, 16, and 28.
Occurrence of TEAEs from baseline to Week 28. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between week 0 and 28, as specified for each endpoint. |
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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 | No |
E.8.1.3 | Single blind | Yes |
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 |
subject- and assessor-blinded |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 69 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 | No |
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 |
Australia |
Austria |
Belgium |
Denmark |
France |
Sweden |
United Kingdom |
Netherlands |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
|
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
|
Last visit of the last subject at global level. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |