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 |
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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 | 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.1.2 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 | 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 |
The primary objective is to evaluate the efficacy of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
- To evaluate the safety and tolerability of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis.
- To evaluate the pharmacokinetics (PK) of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis. |
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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 |
Optional Biopsy Sub-study
Optional Pharmacokinetic Sub-study
Optional Photography Sub-study |
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E.3 | Principal inclusion criteria |
1. Male or female, ≥18 and ≤70 years of age at the time of Visit 1 (Screening Visit)
2. Have a history of moderate to severe plaque psoriasis for at least 6 months prior to Visit 1
3. Subjects with moderate to severe plaque psoriasis covering ≥10% BSA, with a PASI ≥12 and sPGA score ≥3 at Visit 1 and Visit 2 (baseline)
4. Body Mass Index (BMI) ≤40 kg/m^2 at Visit 1
5. Females may participate in the study if they are either surgically sterile, or post-menopausal or if of childbearing potential, use appropriate contraception methods described in the protocol for the duration of the study and for at least 30 days after the last dose of study drug.
Note: female subjects must not donate eggs for the duration of the study and for at least 12 weeks after the last dose of study drug. |
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E.4 | Principal exclusion criteria |
1. History of the discontinuation of biologic therapies (including marketed and investigational drugs) directly targeting IL-17A, IL-17A/F, IL-17 receptor A, IL-12/IL-23p40 or IL-23p19 due to lack of efficacy, according to the Investigator’s judgement
Note: If subjects discontinued these therapies due to other reasons (e.g., safety, preference of other medication, cost, insurance coverage, remission), the subjects may participate in the study according to the Investigator’s judgment.
2. Prior exposure to ROR-γ inhibitors
3. Presence of erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis or other skin conditions (e.g., clinically-significant eczema or severe acne) that could interfere with study evaluations at Visit 1
Note: Subjects with psoriatic arthritis may participate in the study if criteria for cutaneous severity of psoriasis, as well as all other study restrictions required by the protocol are met.
4. History or presence of any itch due to underlying conditions other than plaque psoriasis which cause or influence pruritus of the skin (e.g., drug-induced pruritus, significant other systemic diseases with itch) within 12 months prior to Visit 1
5. Does not meet all protocol-specified laboratory test criteria or study restrictions, including previous/concomitant medication restriction criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Parameters:
Proportion of subjects achieving a minimum 75% improvement from baseline in the PASI (PASI-75) at end of treatment (EOT) |
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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) |
Secondary Efficacy Parameters:
• Proportion of subjects achieving PASI-50/PASI-75/PASI-90;
• Percent change from baseline in PASI;
• Proportion of subjects achieving sPGA score of 0 or 1;
• Change from baseline in sPGA score;
• Percent change from baseline in BSA;
• Change from baseline in Skindex-16;
• Change from baseline in Itch Numeric Rating Scale (NRS);
• Change from baseline in each domain score/questionnaire of the Skindex-16.
Exploratory Efficacy Parameters:
• Percent change from baseline in psoriasis scalp severity index (PSSI);
• Change from baseline in Pain NRS for PsA.
Exploratory Pharmacodynamic Parameters:
• Change from baseline in levels of cytokines mRNA expression in the biopsy target psoriatic lesions at EOT;
• Change from baseline in histopathological parameters in the biopsy target psoriatic lesion at EOT.
Safety Assessments:
• Number and proportion of subjects with adverse events (AEs), type and severity of AEs, change from baseline in safety laboratory, vital sign and electrocardiogram (ECG) parameters.
Pharmacokinetic Assessments:
• Trough plasma levels of JTE-451;
• Relationship between the JTE-451 dose (exposure) and response may be assessed (exploratory). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Parameters: Weeks 2, 4, 8, 12, 16, 20 and EOT, unless otherwise stated
Exploratory Efficacy Parameters: Weeks 2, 4, 8, 12, 16, 20 and EOT, unless otherwise stated
Exploratory Pharmacodynamic Parameters: Baseline and EOT
Safety Assessments: From baseline until Week 16
Pharmacokinetic Assessments: Trough plasma levels of JTE-451 |
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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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Canada |
Germany |
Poland |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |