First-in-Human Study of Oral SDC-1801 in Healthy Adults and Adults with Plaque Psoriasis (Part 4 - Adults with Plaque Psoriasis)

INTERVENTION: Part 4 of this study will have a randomised, double‐blind design, and consist of 2 sequential dose cohorts (Cohorts Psoriasis Dose i and Psoriasis Dose ii). Each cohort will consist of 12 participants with moderate to severe plaque psoriasis. Cohort Psoriasis Dose i will only start after the Safety Review Committee (SRC) meeting has taken place to review the available safety, tolerability, and pharmacokinetic (PK) data from all previous cohorts, and the members of the SRC have decided that it is appropriate to initiate Part 4 of the study and the doses that should be used. The doses that are selected for Part 4 of the study will have been demonstrated to be well tolerated, and exposure at those doses would not have exceeded that seen at the no‐observed‐adverse‐effect level (NOAEL) (in the most sensitive toxicology species, the dog) in other Parts of the study. Recruitment to Cohort Psoriasis Dose ii may start as soon as recruitment to Cohort Psoriasis Dose i has completed. The participants in each cohort will be randomised in a 3:1 ratio to multiple doses of SDC‐1801 or matching placebo. SDC‐1801 or placebo will be administered as an oral capsule/s OD (once daily) or BID (twice daily) for 14 days. On Day 1 and Day14 (to minimise any effect of food on PK assessments), the study drug will be administered after an overnight fast of at least 8 hours and if a BID dose regimen is chosen, the second dose will be administered at approximately 8pm following a 4‐hour fast. To check dosing compliance, while in the Clinical Pharmacology Unit (CPU), participants will have their mouths examined following dosing to determine that the dose has been swallowed. For dosing that occurs outside of the CPU, dosing visits will be conducted as nurse home visits or study staff will te CONDITION: Inflammatory and Immune System ‐ Autoimmune diseases Plaque Psoriasis; ; Plaque Psoriasis PRIMARY OUTCOME: Primary Outcome 1; ; Vital Signs:; ; Body temperature (via typmanic thermometer), pulse rate (via automated device), respiratory rate (via observation), systolic and diastolic blood pressure (via an automated device) and blood oxygen saturation (via pulse oximeter) will be measured at the following timepoints.; [‐ Screening; ‐ Day ‐1; ‐ Day 1: pre‐dose, 2h, 4h, 8h, 12h; ‐ Day 2: 24 hours post first dose; ‐ Day 4: 72 hours post first dose; ‐ Day 6: 120 hours post first dose; ‐ Day 7: 144 hours post first dose; ‐ Day 10: 216 hours post first dose; ‐ Day 12: 264 hours post first dose; ‐ Day 14: pre‐dose, 2h, 4h, 8h, 12h; ‐ Day 15: 24 hours post Day 14 dose; ‐ Day 17: 72 hours post Day 14 dose; ‐ Day 19: 120 hours post Day 14 dose; ‐ Day 28 post first dosing visit: follow‐up visit] Primary Outcome 2 ; ; ECG:; ; ECGs will be recorded via the use of a standard 12 lead ECG machine, with measurements taken in triplicate, at the following time points. ; [‐ Screening; ‐ Day 1: pre‐dose, 1h, 2h, 4h, 6h, 8h and 12h; ‐ Day 2: 24h post‐dose; ‐ Day 14: pre‐dose, 1h, 2h, 4h, 6h, 8h and 12h; ‐ Day 15: 24h post Day 14 dose; ‐ Day 28 post first dosing visit: follow‐up visit] To evaluate the safety and tolerability of 14 days dosing with oral SDC‐1801 compared with placebo in participants with plaque psoriasis. Withdrawal information, and the reasons for withdrawal will be collected via the eCRF.[Participants in the study will have the following safety assessments conducted from their presentation to the clinic at Screening (up to 28 days prior to dosing) to Day 28 following their first dose. ] SECONDARY OUTCOME: Primary Outcome 3: ; ; Clinical Laboratory Samples: ; ; Clinical Laboratory samples of blood and urine (for haematology, blood chemistry and urinalysis) will be collected and measured at: [‐ Screening ; ‐ Pre‐dose (day 1) ; ‐ Day 2 (24 hours) post‐dose ; ‐ Day 6 (120 hours) post‐dose ; ‐ Day 10 (216 hours) post‐dose ; ‐ Day 12 (264 hours) post‐dose ; ‐ Day 15 (24 hours) post‐Day 14 dose ; ‐ Day 28 (post first dosing visit): follow‐up visit] To evaluate the multiple dose PK of oral SDC‐1801 in adults with psoriasis. ; ; The following parameters, where appropriate, will be determined for SDC‐1801 and its metabolites by noncompartmental analysis using individual concentration‐time profiles in plasma and urine: ; ; • Plasma: Cmax, Tmax, C24, Cav, AUC24, AUC from the time of dosing to time t (AUC0‐t), AUC0‐8, t½, terminal rate constant, Rac. ; ; • Urine: Ae tau and CL r. ; • Dose‐standardized parameters (Cmax/dose, C24h/dose or CT/dose, AUC/dose and Ae%).[PK samples for SDC‐1801 and its metabolites will be taken from participants in Part 4 of the study, at the following timepoints: ; ; ‐ Day 1: pre‐dose, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h post‐first dose ; ‐ Day 2: 24 h post‐first dose ; ‐ Day 4: 72 h post‐first dose ; ‐ Day 6: 120h post‐first dose ; ‐ Day 7: 144h post‐first dose ; ‐ Day 10: 168h post‐first dose ; ‐ Day 12: 264h post‐first dose ; ‐ Day 13: 288h post‐first dose ; ‐ Day 14: pre‐Day 14 dose, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h post Day 14 dose ; ‐ Day 15: 24 hours post Day 14 dose ; ‐ Day 16: 48 hours post Day 14 dose ; ‐ Day 17: 72 hours post Day 14 dose ; ‐ Day 18: 96 hours post Day 14 dose ; ‐ Day 19: 120 hours post Day 14 dose] INCLUSION CRITERIA: 1. Able and willing to comply with the protocol requirements and to sign the ICF as approved by the IEC/IRB, prior to any Screening evaluations. 2. History of plaque psoriasis for at least 6 months prior to the Screening visit. 3. No significant flare in psoriasis for at least 3 months before Screening (information obtained from medical chart, participant's physician, or directly from the participant). 4. Has moderate to severe plaque psoriasis at baseline as defined by a PASI score greater than or equal to 10 and a PGA score greater than or equal to 3 at Screening and Day ‐1. 5. Body surface area (BSA) covered by plaque psoriasis greater than or equal to 10% at Screening and Day ‐1. 6. Must be a candidate for phototherapy or for systemic treatment of psoriasis. 7. Must agree to avoid prolonged exposure to the sun and avoid other ultraviolet light sources (e.g. tanning beds) during the study period and for 7 days after the last dose of study