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] - 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 |
To compare the Psoriasis Area and Severity Index (PASI-75) between doses of ESK-001 and placebo after 12 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
1.To assess the safety and tolerability of ESK-001 dose in moderate to severe psoriasis patients. 2. To characterize the pharmacokinetics (PK) of ESK-001. 3.To assess the response rate in static Physician’s Global Assessment (sPGA) score after 12 weeks of treatment. 4.To assess the response rate in PASI-50,90, and 100 score after 12 weeks of treatment. 5.To compare the response rate in PASI-75 among ESK-001 treatments. 6.To assess the effect on body surface area (%BSA) involved with psoriasis after 12 weeks of treatment. 7.To assess the change in Dermatology Life Quality Index (DLQI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able and willing to provide signed informed consent to participate in this study 2. Males or females, age 18-75 years, inclusive, at the Screening Visit 3. Total body weight >40 kg (88 lb) 4. Diagnosis of plaque psoriasis for ≥6 months 5. Plaques covering ≥10% of body surface area (BSA) 6. Psoriasis area severity index score (PASI) score ≥12 and static Physician’s Global Assessment (sPGA) score ≥3 7. Women of childbearing potential (WOCBP) must agree to adhere to highly effective methods of contraception for the entirety of the study and for 30 days after the last dose of study drug 8. Males who are sexually active with WOCBP must agree to use highly effective methods of contraception for the entirety of the study and for 90 days after the last dose of study drug |
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E.4 | Principal exclusion criteria |
1. Diagnosis of non-plaque psoriasis (guttate, inverse, pustular, erythrodermic, drug induced) 2. Diagnosis of immune-mediated conditions that are commonly associated with psoriasis (e.g., uveitis, inflammatory bowel disease) or other inflammatory skin conditions that may interfere with the study assessment 3. Patients with psoriatic arthritis who are receiving systemic (oral, SC, IM or IV) immunosuppressant medications (including corticosteroids, immunosuppressant biologics) or who has or is expected, in the opinion of the investigator, to develop unstable disease. • Patients who are receiving a stable therapeutic regimen for their psoriatic arthritis that does not include immunosuppressants (e.g. NSAIDs) may be included in the study 4. Pregnant, lactating, or planning to get pregnant during the study period 5. Has used topical medications/treatments that could affect psoriasis evaluation within 2 weeks of the first administration of study drug 6. Has received phototherapy or any systemic medications/treatments that could affect psoriasis evaluation within 4 weeks of Study Day 1 7. Has received any therapeutic agent targeted to: IL-12or IL-23 within 6 months, IL-17 within 4 months, or any TNFα inhibitor(s) within 2 months of first administration of study drug 8. Is currently receiving or has received any systemic immunosuppressants or immunomodulatory drugs (e.g., methotrexate, cyclosporine) within 4 weeks of the first administration of study drug or 5 half-lives whichever is longer 9. Has received agents that modulate B cells (e.g., rituximab, ocrelizumab) within 6 months of first administration of study drug 10. Has received agents that modulate T cells (e.g., abatacept, alemtuzumab) within 3 months of first administration of study drug 11. Has received JAK inhibitors (e.g., baricitinib, tofacitinib) or TYK2 inhibitors within 4 weeks of first administration of study drug 12. History of lack of clinical response to any therapeutic agent targeted to IL-12, IL-17 or IL-23 (e.g., ustekinumab, risankizumab, secukinumab, ixekizumab) at approved doses after at least 3 months of treatment 13. History of lack of clinical response, in the Investigator’s opinion, to 2 or more biologic therapies at approved doses after at least 3 months of treatment 14. Has received any investigational agent, within 30 days or 5 half-lives (whichever is longer) of any study drug or is currently enrolled in an investigational study 15. Is currently receiving proton pump inhibitors such as omeperazole or esomeprazole. It is acceptable to substitute a histamine 2 receptor blocking drug or oral antacids prior to Study Day 1 16. Patients with QTcF >450 msec (males) or >470 msec (females) at screening 17. Unstable cardiovascular disease, defined as a recent clinical deterioration (e.g., unstable angina, rapid atrial fibrillation) or a cardiac hospitalization within the last 3 months • Patients requiring medications to treat underlying stable chronic cardiovascular disease, including but not limited to β-blockers, should be on a stable dose for at least 4 weeks before Study Day 1 18. Active herpes viral infection, including herpes simplex 1 and 2 and herpes zoster identified on examination and/or medical history within 2 months of administration of study drug 19. Patients with hepatitis C virus (HCV), or hepatitis B virus (HBV) or human immunodeficiency virus (HIV) or active or inadequately treated latent tuberculosis (TB) infection at screening 20. Has any of the following lab abnormalities: • Absolute neutrophil count <1.5 X 10^9/L • Hemoglobin <9 g/dL • AST/ALT ≥2 x upper limit of normal (ULN) • Albumin <3 g/dL • Total bilirubin ≥2 x ULN (patients with a history of Gilbert’s syndrome are not eligible) • Glomerular filtration rate <50 (Cockcroft and Gault method) 21. History of any immune-mediated or inflammatory medical condition for which patient requires current systemic (oral, SC, IM or IV) corticosteroids • Stable doses of inhaled corticosteroids for treatment of asthma are allowed 22. History of serious bacterial, fungal, or viral infections that led to hospitalization and IV antibiotic treatment within 90 days prior to screening, or any recent serious infection requiring antibiotic treatment within 30 days of Study Day 1 23. Known current malignancy or current evaluation for a potential malignancy or history of malignancy within the past 5 years prior to screening, except for adequately treated basal cell skin carcinoma, carcinoma in situ of the cervix and breast ductal carcinoma in situ 24. Live vaccines (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and bacillus Calmette-Guérin) within 4 weeks of Study Day 1 25. Patient has a known hypersensitivity to any component of the study drug 26. Patient has planned surgery during the study period Please refer to section 5.2 Inclusion criteria of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of patients with moderate to severe psoriasis achieving ≥75% reduction in PASI score at 12 weeks between doses of ESK-001 and placebo |
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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) |
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) • Plasma concentrations and PK parameters of ESK-001 • Proportion of patients achieving an sPGA score of “0” (“cleared”) or “1” (“minimal”) after 12 weeks of ESK-001 treatment compared with placebo • Proportion of patients achieving PASI-50, 90, and 100 after 12 weeks of ESK-001 treatment compared with placebo • Proportion of patients achieving PASI-75 at 12 weeks compared among the ESK-001 treatments • Change from baseline in %BSA after 12 weeks of ESK-001 treatment compared with placebo. •Change from baseline in DLQI at Week 12 in ESK-001 compared with placebo |
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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 | Yes |
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) | 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 | No |
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 | 6 |
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 | 15 |
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 |
United States |
Poland |
Czechia |
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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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |