Netherton Syndrome
Conditions
Keywords
First-in-human, Single ascending dose, Multiple ascending dose, Pharmacokinetics, Placebo control, Netherton syndrome
Brief summary
This is a first-in-human, Phase 1/1b, 4-part study that includes the evaluation of safety, tolerability, pharmacokinetics (PK), and immunogenicity of BCX17725 when administered via single and multiple doses in healthy adult participants (Parts 1 and 2), and multiple doses in adult participants with Netherton syndrome (Part 3). In Part 4, the effectiveness, safety, and tolerability of BCX17725 when administered via multiple IV and/or SC doses through 12 weeks will be evaluated in adult and adolescent participants with Netherton syndrome.
Detailed description
Parts 1 and 2 are randomized, placebo-controlled, single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study parts, respectively, in healthy participants. Part 3 will evaluate multiple dose administrations in participants with Netherton syndrome in an open-label design. Part 4 will evaluate multiple administrations of BCX17725 in participants with Netherton syndrome in an open-label study design over 12 weeks, with an 8-week post-treatment follow-up period.
Interventions
DRUGBCX17725
BCX17725 for injection
DRUGPlacebo
Placebo for injection
Sponsors
BioCryst Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Parts 1 and 2 will be blinded; Parts 3 and 4 will be open label
Intervention model description
In Parts 1 and 2, participants will be randomized to BCX17725 or placebo under double-blind conditions. In Parts 3 and 4, participants will receive open-label BCX17725.
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Male or non-pregnant, non-lactating female aged 18 to 55 years, inclusive (Parts 1 and 2), 18 to 65 years, inclusive (Part 3), or 12 to 65 years, inclusive (Part 4) * Confirmed diagnosis of Netherton syndrome (Parts 3 and 4) * IGA score of ≥ 3 (Parts 3 and 4) and IASI score of ≥ 16 (Part 4) * BMI between 18 and 30 kg/m\^2, inclusive (Parts 1 and 2) * Estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min/1.73 m\^2 (Parts 1 and 2) or ≥ 60 mL/min/1.73 m\^2 (Part 3) * Agree to follow the protocol contraception requirements from screening until 90 days after the last dose of study drug * In the opinion of the investigator, expected to adequately comply with all required study procedures and restrictions for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | From screening through EOS (ie, through Day 78 in Parts 1 and 3, and Day 106 in Part 2) | Incidence of TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) from screening through end-of-study (EOS) in each study part |
| Change from baseline in Ichthyosis Area and Severity Index (IASI) score at Week 12 (Part 4) | From baseline to Week 12 | IASI measures the severity of erythema (IASI-E) and scaling (IASI-S); the maximum sub-scores for the IASI-E and IASI-S being 24, and the maximum total IASI score being 48. Higher scores indicate worse clinical outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed serum concentration (Cmax) | Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3) | Cmax of BCX17725 |
| Time to maximum observed serum concentration (Tmax) | Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3) | Time to Cmax of BCX17725 |
| Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUC0-t) | Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3) | AUC0-t of BCX17725 |
| Terminal elimination half-life (t1/2) | Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3) | Terminal elimination half-life (t1/2) of BCX17725 |
| Number of participants who are anti-drug antibody (ADA)-positive (baseline and post-baseline) and number of participants who have treatment-emergent ADAs | Day 1 pre-dose and up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3) | Incidence of ADAs to BCX17725 |
| Change from baseline in Investigator Global Assessment (IGA) score at Week 12 (Part 4) | From baseline to Week 12 | IGA assesses the overall severity of a participant's NS skin disease based on a 5-point scale (0, clear; 1, almost clear; 2, mild; 3, moderate; and 4, severe). Higher scores indicate worse clinical outcome. |
| Change from baseline in Worst Itch Numerical Rating Score (NRS) at Week 12 (Part 4) | From baseline to Week 12 | Worst Itch Numerical Rating Scale (NRS) is a self-rated, single-item scale designed for assessing the worst itch in the past 7 days. The scale uses an 11-point NRS, scored from 0 (no itch) to 10 (worst possible itch). Higher scores indicate worse clinical outcome. |
| Incidence of TEAEs (Part 4) | From baseline through Week 20 | Incidence of TEAEs as assessed by CTCAE |
| Serum concentrations of BCX17725 (Part 4) | From baseline through Week 20 | Serum concentrations of BCX17725 |
Countries
Australia, France, Germany, Netherlands, United States
Contacts
CONTACTBioCryst Pharmaceuticals, Inc.
Outcome results
None listed