Atopic Dermatitis, Healthy Participants
Conditions
Keywords
IL-25, Monoclonal antibody, First-in-human, Multiple ascending dose, Single ascending dose, Atopic dermatitis, Healthy Participant
Brief summary
This first-in-human study evaluates BYN-001, a humanized IgG1 monoclonal antibody targeting interleukin-25 (IL-25), a cytokine implicated in atopic dermatitis. Parts A and B are randomized, double-blind, placebo-controlled single and multiple ascending dose cohorts in healthy adults, that will assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of BYN-001. Part C will assess BYN-001 in adults with moderate to severe atopic dermatitis.
Detailed description
Atopic dermatitis (AD) is a common chronic inflammatory skin disease for which current type 2 cytokine-targeted biologics leave a substantial proportion of patients with an inadequate response or residual pruritus. IL-25 acts upstream of type 2 inflammation and has been shown to drive pruritus and epidermal barrier dysfunction. BYN-001 selectively binds and neutralises IL-25 (with a long predicted terminal half-life), supporting an infrequent dosing interval. Part A will consist of a single ascending dose (SAD) design, with administration in up to five cohorts. Part B will consist of a multiple ascending dose (MAD) design, with administration in up to three cohorts. Both parts will enroll healthy participants and will be conducted under a sentinel dosing approach, with dose escalation decisions governed by a Safety Monitoring Committee (SMC) at each escalation step. Part C will enroll participants with moderate to severe AD.
Interventions
BIOLOGICALBYN-001
BYN-001 will be administered by subcutaneous injection. In Part A, a Single Ascending Dose (SAD) design will be implemented across up to five cohorts, with healthy participants receiving a single dose of BYN-001. In Part B, a Multiple Ascending Dose (MAD) design will be implemented with healthy participants receiving multiple doses of BYN-001.
DRUGPlacebo
Part A SAD healthy participants will receive a single subcutaneous injection of placebo. Part B MAD healthy participants will receive multiple doses of subcutaneous injection of placebo.
Sponsors
Bionyra Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blinded study design. Site staff, participants and the Sponsor/CRO may become unblinded within 2 weeks of interim analysis completion.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Part A and B Key Inclusion Criteria: * Age 18-55 years of age * Must be in good health with no significant medical conditions * Willing and able to attend all study visits and comply with study requirements * Able and willing to provide written informed consent Part A and B
Exclusion criteria
* Evidence of clinically significant condition or disease * Any physical or psychosocial condition that prohibits study completion * Know history of illicit drug use or abuse, alcoholism and/or smoking more than -5 cigarettes a day in the prior 3 months * History of sever allergic reactions of hypersensitivity Part C Inclusion Criteria * Age 18-55 years of age * Must be in good health with no significant medical conditions * Willing and able to attend all study visits and comply with study requirements * Able and willing to provide written informed consent * Documented chromic atopic dermatitis within 1 year prior to screening * Moderate to severe atopic dermatitis Part C Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AEs) | From first dose through end of study (up to Week 48 for BYN-001 recipients; up to 2 weeks post-unblinding for placebo recipients) | Includes clinically relevant findings from clinical laboratory tests (haematology, urinalysis, blood chemistry), physical examination, vital signs, and 12-lead ECG. Assessed separately for the healthy-volunteer participants (Part A and B) and the AD participants in Part C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters of BYN-001 | Serial PK sampling per the Schedule of Assessments, through Week 48 | Peak plasma concentration of BYN-001 may be calculated if deemed necessary. |
| Incidence of anti-drug antibodies (ADA) to BYN-001 | Baseline through Week 48 | Immunogenicity assessed using a validated methods. |
| Titer of anti-drug antibodies (ADA) to BYN-001 | Baseline through Week 48 | Immunogenicity assessed using validated methods. |
Contacts
CONTACTJames McCarthy, Prof.
Outcome results
None listed