A Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BCX17725
- Registration Number
- NCT06539507
- Lead Sponsor
- BioCryst Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 78
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 - BCX17725 single dose BCX17725 Participants randomized to BCX17725 will receive BCX17725 as a single dose in sequential ascending dose cohorts Part 1 - placebo single dose Placebo Participants randomized to placebo will receive placebo as a single dose Part 2 - BCX17725 multiple doses BCX17725 Participants randomized to BCX17725 will receive BCX17725 as multiple doses in sequential ascending dose cohorts Part 2 - placebo multiple doses Placebo Participants randomized to placebo will receive placebo as multiple doses Part 3 - BCX17725 multiple doses BCX17725 Participants will receive BCX17725 as multiple doses Part 4 - BCX17725 multiple doses BCX17725 Participants will receive BCX17725 as multiple doses
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Investigative site
🇦🇺Brisbane, Queensland, Australia
Investigative site🇦🇺Brisbane, Queensland, Australia