A Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BCX17725

Phase 1RecruitingNCT06539507

BioCryst Pharmaceuticals78 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Netherton Syndrome

Interventions

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (5)

Investigative site

New Haven, Connecticut, United States

RECRUITING

Investigative site

Indianapolis, Indiana, United States

RECRUITING

Investigative site

Sydney, New South Wales, Australia

RECRUITING

Investigative site

Brisbane, Queensland, Australia

ACTIVE_NOT_RECRUITING

Investigative site

Brisbane, Queensland, Australia

RECRUITING

Outcomes

Primary Outcomes

Incidence of treatment-emergent adverse events (TEAEs)

Incidence of TEAEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) from screening through end-of-study (EOS) in each study part

Time frame: From screening through EOS (ie, through Day 78 in Parts 1 and 3, and Day 106 in Part 2)

Change from baseline in Ichthyosis Area and Severity Index (IASI) score at Week 12 (Part 4)

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.

Time frame: From baseline to Week 12

Secondary Outcomes

Maximum observed serum concentration (Cmax)

Cmax of BCX17725

Time frame: Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3)

Time to maximum observed serum concentration (Tmax)

Time to Cmax of BCX17725

Time frame: Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3)

Area under the serum concentration-time curve (AUC) from time 0 to the time of last measurable concentration (AUC0-t)

AUC0-t of BCX17725

Time frame: Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3)

Terminal elimination half-life (t1/2)

Terminal elimination half-life (t1/2) of BCX17725

Time frame: Up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3)

Number of participants who are anti-drug antibody (ADA)-positive (baseline and post-baseline) and number of participants who have treatment-emergent ADAs

Incidence of ADAs to BCX17725

Time frame: Day 1 pre-dose and up to Day 64 (Part 1), Day 92 (Part 2), and Day 78 (Part 3)

Change from baseline in Investigator Global Assessment (IGA) score at Week 12 (Part 4)

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.

Time frame: From baseline to Week 12

Change from baseline in Worst Itch Numerical Rating Score (NRS) at Week 12 (Part 4)

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.

Time frame: From baseline to Week 12

Incidence of TEAEs (Part 4)

Incidence of TEAEs as assessed by CTCAE

Time frame: From baseline through Week 20

Serum concentrations of BCX17725 (Part 4)

Serum concentrations of BCX17725

Time frame: From baseline through Week 20

A Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BCX17725

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts