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

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).

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.

Study Overview

• Status: Recruiting
• Conditions: Moderate to Severe Atopic Dermatitis
• Intervention / Treatment: Drug: SYX-5219 Oral Capsule

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.

• Study Type: Interventional
• Enrollment (Estimated): 149
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sitryx Therapeutics; Phone Number: +44 (0)1865 648401; Email: info@sitryx.com
• Study Contact Backup: Name: Sitryx Therapeutics; Phone Number: +44 (0) 1865 648401; Email: info@sitryx.com

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1404
    • Recruiting
    • Sitryx Clinical Site
• Denmark
  • Herlev
    • Herlev, Herlev, Denmark, 2730
      • Not yet recruiting
      • Sitryx Clinical Site
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Sitryx Clinical Site
  • Frankfurt, Germany, 60596
    • Recruiting
    • Sitryx Clinical Site
  • Freiburg im Breisgau, Germany, 79106
    • Active, not recruiting
    • Sitryx Clinical Site
• Ireland
  • Dublin, Ireland, D08 NHY1
    • Recruiting
    • Sitryx Clinical Site
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Recruiting
    • Sitryx Clinical Site
  • Merthyr Tydfil, United Kingdom, CF48 4DR
    • Recruiting
    • Sitryx Clinical Site
• United States
  • Arkansas
    • Arkansas City, Arkansas, United States, 72117
      • Recruiting
      • Sitryx Clinical Site
  • California
    • Fremont, California, United States, 94538
      • Recruiting
      • Sitryx Clinical Site
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Recruiting
      • Sitryx Clinical Site
  • Ohio
    • Boardman, Ohio, United States, 44512
      • Recruiting
      • Sitryx Clinical Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Recruiting
      • Sitryx Clinical Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • Recruiting
      • Sitryx Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Single Ascending Dose (SAD); Single dose of SYX-5219 (active or matching placebo) administered on Day 1 for all cohorts and Day 1 of each treatment period for food effect cohorts (in fasted and fed conditions).	Drug: SYX-5219 Oral Capsule; Oral Capsule to be administered at each specific dose level within each cohort
Experimental: Part 2 Multiple Ascending Dose (MAD); Multiple doses of SYX-5219 (active or matching placebo) administered once or twice daily for all cohorts.	Drug: SYX-5219 Oral Capsule; Oral Capsule to be administered at each specific dose level within each cohort
Experimental: Part 3 AD Participants Multiple Doses; Multiple doses of SYX-5219 (active or matching placebo) administered twice daily for multiple dose administration	Drug: SYX-5219 Oral Capsule; Oral Capsule to be administered at each specific dose level within each cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Participants With Treatment-Emergent Adverse Events	The number of participants who reported a treatment-emergent adverse event (TEAE) will be summarised.	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

Outcome Measure	Measure Description	Time Frame
Concentrations of SYX5219 in Plasma	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.	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	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.	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.

Other Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in the Eczema Area and Severity Index (EASI) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Proportion of participants achieving a 50% 75% and 90% reduction of EASI (EASI50 and EASI75 and EASI90) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Proportion of participants achieving a minimum 2- grade improvement from baseline in validated Investigator Global Assessment (vIGA) score to clear (0) or almost clear (1) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Percent change from baseline in peak pruritus numeric rating scale (PP-NRS) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Proportion of participants with ≥3-point and ≥4-point improvement in peak pruritus numeric rating scale - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Percent change from baseline in weekly average of the daily PP-NRS scores - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Percent change from baseline in weekly average of the daily sleep loss scores - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Change from baseline and percent change from baseline in percent atopic dermatitis covering the body surface area (BSA) involvement - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Change from baseline in Dermatology Life Quality Index (DLQI) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.
Change from baseline in Patient Orientated Eczema Measure (POEM) - Part 3	For Part 3: Measured at screening, Day 1, Day 8, Day 15, Day 29, Day 43 & Day 56.

Collaborators and Investigators

• Sponsor: Sitryx Therapeutics Ltd
• Investigators: Study Director: Sitryx Therapeutics, Study Sponsor

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2025
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: SYX-5219-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No