E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-Severe Chronic Plaque Psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate-to-Severe Chronic Plaque 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 | 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 |
Primary Efficacy Objective: To assess the efficacy of tildrakizumab (SCH-900222/MK-3222) (hereafter referred to as MK-3222) compared to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index from baseline (PASI 75 response), and the proportion of subjects with a Physician’s Global Assessment (PGA) score of “clear” or “minimal”, with at least a 2 grade reduction from baseline, at Week 12.
Primary Safety/Tolerability Objective: To assess the safety/tolerability of tildrakizumab (MK-3222) in subjects with moderate-to-severe chronic plaque psoriasis at Week 12.
Extension Study: To assess long-term safety and tolerability of tildrakizumab (MK-3222) in subjects with moderate-to-severe chronic plaque psoriasis for a minimum of 4 years. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of tildrakizumab (MK-3222) compared to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of subjects with at least 90% improvement in PASI from baseline (PASI 90 response) at Week 12. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject (≥18 years of age) with a clinical diagnosis of moderate-to-severe chronic plaque psoriasis (defined by ≥10% body surface area [BSA] involvement, at least "moderate" [≥3] score on the PGA scale, and PASI score of ≥12 at Baseline [Visit 2]). - Subject must have a diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator). - Subject must be considered a candidate for phototherapy or systemic therapy. |
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E.4 | Principal exclusion criteria |
- Subject has predominantly non-plaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis. - Subject with current or history of severe psoriatic arthritis and is well-controlled on current therapy. - Women of childbearing potential who are pregnant, intend to become pregnant (within 6 months of completing the trial), or are lactating. - Subject who is expected to require topical therapy, phototherapy, or systemic therapy during the trial. - Subject with presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or severe infection (e.g. pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening. - Subject with any previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors, including p40, p19 and IL-17 antagonists. - Subject with evidence of active or untreated latent tuberculosis (TB) according to screening criteria specified in the protocol. Prophylactic treatment for latent TB as per local guidelines must be initiated at least 4 weeks prior to first administration of study medication. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints - Proportion of subjects with PASI 75 response at Week 12 - Proportion of subjects with a PGA score of "clear" or "minimal", with at least a 2 grade reduction from baseline, at 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) |
Key Secondary Efficacy Endpoint - Proportion of subjects with PASI 90 response at Week 12 - Proportion of subjects with PASI 100 response at Week 12 Other Secondary Efficacy Endpoints Part 1 (Weeks 0-12) - Change from baseline in DLQI from baseline at Week 12 - Proportion of subjects with a DLQI score of 0 or 1 at Week 12 - Proportion of subjects with ACR 20, ACR50 and ACR70 response at Week 12 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change from baseline in HAQ at Week 12 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change from baseline in PGAP (VAS for pain) at Week 12 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change and percent change from baseline in PASI score at Week 12 Parts 2 and 3 (Weeks 12 - 64) - Proportion of subjects with PASI 75 response at Weeks 28, 40, 52, and 64 - Proportion of subjects with PASI 90 response at Weeks 28, 40, 52, and 64 - Proportion of subjects with PASI 100 response at Weeks 28, 40, 52, and 64 - Proportion of subjects with PGA "clear" or "minimal", with at least a 2 grade reduction from baseline, at Weeks 28, 40, 52, and 64 - Change from baseline in DLQI response at Weeks 28, 40, 52 and 64 - Proportion of subjects with DLQI score of 0 or 1 at Weeks 28, 40, 52 and 64 - Proportion of subjects who relapse following withdrawal of tildrakizumab (MK-3222) treatment among re-randomized tildrakizumab (MK-3222) responders over time - Proportion of subjects with PASI 75 response following withdrawal of tildrakizumab (MK-3222) treatment among re-randomized tildrakizumab (MK-3222) responders over time - Proportion of subjects with PGA "clear" or "minimal", with at least a 2 grade reduction from baseline, following withdrawal of tildrakizumab (MK-3222) treatment among re-randomized tildrakizumab (MK-3222) responders over time - Proportion of subjects with rebound of disease following withdrawal of tildrakizumab (MK-3222) treatment among re-randomized tildrakizumab (MK-3222) responders - Proportions of subjects with PASI 75, 90 and 100 responses and the proportion of PGA ("clear" or "minimal"), with at least a 2 grade reduction from baseline, following 12 weeks of re-initiated tildrakizumab (MK-3222) treatment among subjects who relapse after withdrawal of tildrakizumab (MK-3222) treatment - Proportions of partial responders who achieve PASI 75 and the proportion of PGA ("clear" or "minimal"), with at least a 2 grade reduction from baseline, at Weeks 52 and 64 after increasing their dose of tildrakizumab (MK-3222) (from 100 mg to 200 mg) at Week 28 - Proportion of subjects with ACR 20, ACR50 and ACR70 response at Weeks 16, 28, 40, and 64 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change from baseline in HAQ at Weeks 28, 40, and 64 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change from baseline in PGAP (VAS for pain) at Weeks 28, 40, and 64 (applicable only to subjects with concomitant psoriatic arthritis at baseline enrolled at Japanese Investigative sites) - Change and percent change from baseline in PASI score over time |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 |
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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 | 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 | 3 |
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 | 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 |
Japan |
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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |