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

A Phase 1/1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single and Multiple Ascending Doses of BCX17725 in Healthy Participants and Multiple Doses of BCX17725 in Participants With Netherton Syndrome

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.

Study Overview

• Status: Recruiting
• Conditions: Netherton Syndrome
• Intervention / Treatment: Drug: BCX17725; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BioCryst Pharmaceuticals, Inc.; Phone Number: +1 919 859 1302; Email: clinicaltrials@biocryst.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital - Department of Dermatology
      • Contact: Pablo Fernandez-Penas, MD; Phone Number: 02 8890 5686; Email: wslhd-dermatology-clinicaltrials@health.nsw.gov.au
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Recruiting
      • Veracity Clinical Research
      • Contact: Lynda Spelman, MD; Phone Number: 07 3039 1311; Email: trials@veracityclinicalresearch.com.au
    • Brisbane, Queensland, Australia, 4006
      • Active, not recruiting
      • Nucleus Network
• France
  • Paris, France, 75010
    • Not yet recruiting
    • Hôpital Saint-Louis
    • Contact: Emilie Fapong; Phone Number: 01 42 49 40 62; Email: emilie.fapong@aphp.fr
    • Contact: Hafsoiti Hassandjohar; Phone Number: 01 42 49 40 62; Email: hafsoiti.hassandjohar@aphp.fr
• Germany
  • Heidelberg, Germany, 69120
    • Not yet recruiting
    • Universitatsklinikum Heidelberg
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Not yet recruiting
    • Maastricht Universitair Medisch Centrum (MUMC+)
    • Contact: Phone Number: +31 (0)43-3875290; Email: genodermatose@mumc.nl
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus Universitair Medisch Centrum (EMC)
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Not yet recruiting
      • Stanford University School of Medicine
      • Contact: Thomas Buschbacher; Phone Number: 352-278-7603; Email: tbusch@stanford.edu
      • Contact: Chaw-Ning Lee; Phone Number: 650-497-7230; Email: cnlee06@stanford.edu
    • San Diego, California, United States, 92123
      • Recruiting
      • Therapeutics Clinical Research
      • Contact: Hector Bailon; Phone Number: 141 858-571-6800; Email: hbailon@therapeuticsresearch.com
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale Center for Clinical Investigation
      • Contact: Nicole Olszewski; Phone Number: 203-785-5505; Email: nicole.olszewski@yale.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Dermatology CTU
      • Contact: Phone Number: 312-503-5944; Email: NUderm-research@northwestern.edu
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Dawes Fretzin Clinical Research Group, LLC
      • Contact: Joannie Prusa; Phone Number: 108 317-516-5030; Email: jprusa@ecommunity.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - BCX17725 single dose; Participants randomized to BCX17725 will receive BCX17725 as a single dose in sequential ascending dose cohorts	Drug: BCX17725; BCX17725 for injection
Experimental: Part 1 - placebo single dose; Participants randomized to placebo will receive placebo as a single dose	Drug: Placebo; Placebo for injection
Experimental: Part 2 - BCX17725 multiple doses; Participants randomized to BCX17725 will receive BCX17725 as multiple doses in sequential ascending dose cohorts	Drug: BCX17725; BCX17725 for injection
Experimental: Part 2 - placebo multiple doses; Participants randomized to placebo will receive placebo as multiple doses	Drug: Placebo; Placebo for injection
Experimental: Part 3 - BCX17725 multiple doses; Participants will receive BCX17725 as multiple doses	Drug: BCX17725; BCX17725 for injection
Experimental: Part 4 - BCX17725 multiple doses; Participants will receive BCX17725 as multiple doses	Drug: BCX17725; BCX17725 for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	From baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed serum concentration (Cmax)	Cmax of BCX17725	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	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	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	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	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.	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.	From baseline to Week 12
Incidence of TEAEs (Part 4)	Incidence of TEAEs as assessed by CTCAE	From baseline through Week 20
Serum concentrations of BCX17725 (Part 4)	Serum concentrations of BCX17725	From baseline through Week 20

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Multiple ascending dose; First-in-human; Netherton syndrome; Single ascending dose; Placebo control
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Infant, Newborn, Diseases; Skin Diseases; Congenital Abnormalities; Abnormalities, Multiple; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Netherton Syndrome
• Other Study ID Numbers: BCX17725-101; U1111-1303-9510 (Other Identifier: WHO UTN); 2025-521973-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No