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

Sitryx Therapeutics Ltd

Status and phase: Enrolling; Phase 1

Conditions: Moderate to Severe Atopic Dermatitis

Treatments: Drug: SYX-5219 Oral Capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT07558668

SYX-5219-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 149 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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149 participants in 3 patient groups

Part 1 Single Ascending Dose (SAD)

Experimental group

Description:

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).

Treatment:

Drug: SYX-5219 Oral Capsule

Part 2 Multiple Ascending Dose (MAD)

Experimental group

Description:

Multiple doses of SYX-5219 (active or matching placebo) administered once or twice daily for all cohorts.

Treatment:

Drug: SYX-5219 Oral Capsule

Part 3 AD Participants Multiple Doses

Experimental group

Description:

Multiple doses of SYX-5219 (active or matching placebo) administered twice daily for multiple dose administration

Treatment:

Drug: SYX-5219 Oral Capsule