E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque Type Psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 the following 2 treatment paradigms in subjects who have achieved an inadequate (Investigator’s Global Assessment [IGA] ≥2) response to ustekinumab at Week 16:
- Switching to guselkumab treatment.
- Remaining on ustekinumab treatment.
• To assess the safety and tolerability of guselkumab in subjects with moderate to severe plaque-type psoriasis and an inadequate (IGA≥2) response to ustekinumab at Week 16.
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of switching to guselkumab on patient-reported signs and symptoms of psoriasis for subjects with an inadequate (IGA≥2) response to ustekinumab at Week 16.
• To assess the PK and immunogenicity of guselkumab after subcutaneous (SC) administrations in subjects with moderate to severe plaque-type psoriasis and an inadequate (IGA≥2) response to ustekinumab at Week 16.
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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 |
Skin biopsy samples will be collected from a subset of subjects who consent to participate in the optional biopsy substudy. Enrollment in the biopsy study will be optional and will include approximately 120 to 150 subjects at selected study sites. Only subjects who consent to participate in the optional biopsy substudy will undergo collection of these samples. Biopsies will be used for assessment of gene expression and T cell repertoire.
Whole blood samples will be collected from the subset of subjects who consent to participate in the optional biopsy substudy. Peripheral blood mononuclear cells (PBMCs) will be isolated from these samples and processed for immune repertoire analysis with assessment of T-cell receptor clonality.
Protocol version A1, dated 12 February 2015 |
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E.3 | Principal inclusion criteria |
- Have a diagnosis of plaque-type psoriasis (with or without psoriatic arthritis for at least 6 months before the first administration of study drug
- Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (>=) 12 at Screening and at Baseline
- Have an Investigator's Global Assessment (IGA) >=3 at Screening and at Baseline
- Have an involved body surface area (BSA) >= 10 percent (%) at Screening and at Baseline
- Be a candidate for phototherapy or systemic treatment for psoriasis (either naïve or history of previous treatment) |
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E.4 | Principal exclusion criteria |
- Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- Has unstable cardiovascular disease, defined as a recent clinical deterioration (example [eg], unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months
- Currently has a malignancy or has a history of malignancy within 5 years before Screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration)
- Has previously received guselkumab or ustekinumab |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The number of visits at which subjects achieve an IGA response of cleared (0) or minimal (1) and at least a 2 grade improvement (from Week 16) from Week 28 through Week 40, among randomized subjects with an inadequate (IGA≥2) response to ustekinumab at Week 16. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 28 / Week 32/week 36/ week 40 |
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E.5.2 | Secondary end point(s) |
Major Secondary Endpoints
• The number of visits at which subjects achieve a PASI 90 response from Week 28 through Week 40 among randomized subjects with an inadequate (IGA≥2) response to ustekinumab at Week 16.
• The number of visits at which subjects achieve an IGA response of cleared (0) from Week 28 through Week 40 among randomized subjects with an inadequate (IGA≥2) response to ustekinumab at Week 16.
• The proportion of subjects who achieve an IGA of 0 or 1 and at least a 2-grade improvement (from Week 16) at Week 28.
Other Secondary Endpoints
Subjects with an inadequate (IGA≥2) response to ustekinumab at Week 16
• The number of visits at which subjects achieve a PASI 100 response from Week 28 through Week 40.
• The number of visits at which subjects achieve a PASI 75 response from Week 28 through Week 40.
• The average percent improvement from baseline in PASI response between Week 28 and Week 40.
• The number of visits at which subjects achieve a DLQI of 0 or 1 from Week 28 through Week 40 among randomized subjects with DLQI >1 at Week 16.
• The number of visits at which subjects achieve a PSSD symptom score of 0 from Week 28 through Week 40 among randomized subjects with a PSSD symptom score ≥1 at Week 16.
• The number of visits at which subjects achieve a PSSD sign score of 0 from Week 28 through Week 40 among randomized subjects with a PSSD sign score ≥1 at Week 16.
• The number of visits at which subjects achieve a score of 0 for each PSSD individual scale from Week 28 through Week 40 among randomized subjects with PSSD scale score ≥1 at Week 16.
• The proportion of subjects who achieve a PASI 90 response at Week 28.
• The proportion of subjects who achieve an IGA of 0 or 1 and at least a 2-grade improvement (from Week 16) at Week 52.
• The proportion of subjects who achieve a PASI 90 response at Week 52.
• The proportion of subjects who achieve a PSSD symptom score of 0 at Week 52 among randomized subjects with a PSSD symptom score ≥1 at Week 16.
• The proportion of subjects who achieve a PSSD sign score of 0 at Week 52 among randomized subjects with a PSSD sign score ≥1 at Week 16.
• The proportion of subjects who achieve DLQI of 0 and 1 at Week 52 among randomized subjects with DLQI >1 at Week 16.
• The proportion of subjects who achieve each PSSD individual score of 0 at Week 52 among randomized subjects with PSSD scale score ≥1 at Week 16.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 28 / Week 32/week 36/ week 40 / Week 52 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
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 |
Canada |
Germany |
Korea, Republic of |
Poland |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |