A 3-part Study of SYX-5219 in Healthy Volunteers and Participants With Atopic Dermatitis

Official title

A Multi-part, FiH Study in Healthy Participants and Participants With Atopic Dermatitis (AD) to Assess the Safety, Tolerability, Pharmacokinetics (PK) of Single & Multiple Ascending Doses and Selected Dose of SYX-5219 (AD Participants).

Overview

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

• Drug SYX-5219 Oral Capsule
  Oral Capsule to be administered at each specific dose level within each cohort

Primary outcome measures

• The Proportion of Participants With Treatment-Emergent Adverse Events [Time frame: 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.]

Secondary outcome measures (2)

• Concentrations of SYX5219 in Plasma [Time frame: 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.]
• Concentrations of SYX5219 in Urine [Time frame: 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.]

Eligibility criteria

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 exclusion criteria.
• Received treatment(s) as stated in the main study exclusion criteria.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 6 centers

• Sitryx Clinical Site — Arkansas City
• Sitryx Clinical Site — Fremont
• Sitryx Clinical Site — Plainfield
• Sitryx Clinical Site — Boardman
• Sitryx Clinical Site — Philadelphia
• Sitryx Clinical Site — Bountiful

Germany · 3 centers

• Sitryx Clinical Site — Berlin
• Sitryx Clinical Site — Frankfurt
• Sitryx Clinical Site — Freiburg im Breisgau

United Kingdom · 2 centers

• Sitryx Clinical Site — Manchester
• Sitryx Clinical Site — Merthyr Tydfil

Bulgaria · 1 center

• Sitryx Clinical Site — Sofia

Denmark · 1 center

• Sitryx Clinical Site — Herlev

Ireland · 1 center

• Sitryx Clinical Site — Dublin

Identifiers

NCT: NCT07558668 · SYX-5219-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗