Moderate to Severe Atopic Dermatitis
Conditions
Brief summary
The purpose of this study is to evaluate the study drug, SYX-5219, in a multi-part First-in-Human (FiH) study to be conducted in healthy volunteers and participants with Atopic Dermatitis (AD). The objectives of this study are to determine the safety, tolerability and levels of SYX-5219 in the blood and urine when SYX-5219 is given in each part of the study (SAD, MAD, Food Effect and Participants with AD). The study will be split into up to 3 parts as follows: * Part 1 - Single Ascending Dose (SAD) and Food Effect in healthy volunteers * Part 2 - Multiple Ascending Dose (MAD) in healthy volunteers * Part 3 - Multiple Dose in Participants with AD - enrolling up to 45 males and females with a confirmed diagnosis of AD of at least 6 months, evaluating multiple dose administrations of SYX-5219 or placebo daily over a period of 42 days.
Detailed description
This is a multi-part, adaptive, Phase 1, double-blind, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of SYX-5219 following single ascending doses (SAD), multiple ascending doses (MAD), and selected dosing in participants with atopic dermatitis (AD). Parts 1 and 2 will be conducted at a single site in the UK. Part 3 will be conducted globally at multiple sites. Part 1 (Single Ascending Dose & Food Effect) Part 1 (SAD) will enrol up to 48 healthy participants in cohorts (3:1, active:placebo). Participants will receive single doses of SYX-5219, with a food effect evaluation including a second dosing period following washout. Part 2 (Multiple Ascending Dose) Part 2 (MAD) will enrol up to 24 healthy participants in cohorts (3:1, active:placebo). Participants will receive multiple doses of SYX-5219 over a defined treatment period. Part 3 (AD Participants) Part 3 will enrol up to 45 participants with AD across multiple global sites. Participants will be randomised (2:1) to receive SYX-5219 or placebo for up to 42 days. Prior exposure to targeted systemic therapy will be limited. Study assessments will include safety and exploratory efficacy evaluations during treatment and follow-up.
Interventions
DRUGSYX-5219 Oral Capsule
Oral Capsule to be administered at each specific dose level within each cohort
Sponsors
Sitryx Therapeutics Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Parts 1 \& 2 * Healthy male and female participant, between ≥ 18 to ≤ 65 years of age, inclusive, with a BMI of body mass index (BMI) of 18-32 kg/m2. * Female participant of non-childbearing potential or female of childbearing potential that is sexually abstinent. * No clinically significant abnormalities in laboratory, vital signs or ECG measurements. Part 3 * Male and female participants with clinically confirmed diagnosis of active AD, between ≥ 18 to ≤ 65 years of age, inclusive, with a BMI of body mass index (BMI) of ≤40 kg/m2. * Meet minimum AD entry criteria; * AD covering ≥10% of the body surface area (BSA) at screening and baseline. * Eczema Area and Severity Index (EASI) score ≥16 at screening and baseline. * Validated Investigator's Global Assessment (vIGA) score of ≥ 3 (moderate) at screening and baseline. * Peak Pruritus NRS score of ≥ 4 at screening and baseline.
Exclusion criteria
Parts 1 \& 2 • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 35 days or 5 half-lives (whichever is longer) prior to the first dose of IMP. Part 3 * Any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the Investigator, put the participant at undue risk. * Has medical history as stated in the main study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Treatment-Emergent Adverse Events | Adverse events are collected from the date of consent until up to 10 days after the dose in Part 1 (Day 11), 14 days after the last dose in Part 2 (Day 28) and up to Day 56 in Part 3. | The number of participants who reported a treatment-emergent adverse event (TEAE) will be summarised. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of SYX5219 in Plasma | For Part 1: 14 timepoints from pre-dose Day 1 up to 120 h post-dose Day 6. For Part 2: 28 timepoints from pre-dose Day 1 up to Day 19. For Part 3: 8 timepoints from pre-dose Day 1 up to Day 56. | Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for SYX-5219. This endpoint will report the summary of derived pharmacokinetic parameters for participants in all parts of the study. |
| Concentrations of SYX5219 in Urine | For Part 1: continuous urine collection from Day 1 up to 48 hr post-dose on Day 2. For Part 2: continuous urine collection from Day 1 up to 48 hr post-dose on Day 2 and Day 14 up to 48 hr post-dose on Day 16. | Urine samples were obtained in order to evaluate defined urine pharmacokinetic parameters for SYX-5219. This endpoint will report the summary of derived pharmacokinetic parameters for participants in Part 1 and Part 2 of the study. |
Countries
Bulgaria, Denmark, Germany, Ireland, United Kingdom, United States
Contacts
CONTACTSitryx Therapeutics
STUDY_DIRECTORSitryx Therapeutics
Study Sponsor
Outcome results
None listed