A Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome

NCT05979831 | Terminated Phase 1 FDA Drug

• 2 other identifiers: DS2325-1192022-502853-32-00
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Netherton Syndrome (NS) is a severe rare disease characterized by generalized scaling, erythema, and epidermal barrier defects. This study assessed the safety, pharmacokinetics (PK), and efficacy of DS-2325a in patients with NS.

Conditions

Netherton Syndrome

Keywords

Netherton Syndrome; DS-2325a

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events

  Screening up to Week 45 (end of study)

Secondary Outcomes (7)

• Pharmacokinetic Parameter Trough Concentration (Ctrough)

  Main Phase: Baseline and predose of Weeks 3, 5, 7, 9, and 11; Extension Phase: Predose of Weeks 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, and 45

• Mean Ichthyosis Area Severity Index (IASI) Scores

  Screening; Observational: Predose of Weeks 1, 5, and 9; Main Phase: Baseline, predose of Weeks 3, 5, 7, 9, and 11; Extension Phase, predose of Weeks 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

• Mean Investigator Global Assessment (IGA) Scores

  Screening; Observational: Predose of Weeks 1, 5, and 9; Main Phase: Baseline, predose of Weeks 3, 5, 7, 9, and 11; Extension Phase, predose of Weeks 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

• Mean Itch Numerical Rating Scale (NRS) Scores

  Screening; Observational: Predose of Weeks 1, 5, and 9; Main Phase: Baseline, predose of Weeks 3, 5, 7, 9, and 11; Extension Phase, predose of Weeks 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

• Skindex-29 Responses

  Screening; Observational: Predose of Weeks 1, 5, and 9; Main Phase: Baseline, predose of Weeks 3, 5, 7, 9, and 11; Extension Phase, predose of Weeks 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

Study Arms (2)

DS-2325a

EXPERIMENTAL

Participants will be randomized to receive a single initial ("loading") dose of DS-2325a (Week 1) followed by ("maintenance") doses for a total of 12 weeks (Main Phase). Participants will receive DS-2325 doses for a total of 24 weeks (Extension Phase).

Drug: DS-2325a

Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive a single initial loading dose of placebo followed by maintenance doses of placebo for a total of 12 weeks (Main Phase).

Other: Placebo

Interventions

DS-2325a DRUG

Main Phase and Extension Phase: Loading IV dose followed by maintenance SC doses

DS-2325a

Placebo OTHER

Main Phase: IV infusion followed by SC doses

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged 18 to 65 years with clinical diagnosis of NS including at least 3 out of the 4 following clinical criteria:
• Neonatal erythroderma
• Bamboo hair and/or alopecia
• Chronic atopy specified as food allergy and/or asthma and/or rhino-conjunctivitis and/or eczema for at least 2 years
• Ichthyosis linearis circumflexa or scaling erythroderma or equivalent
• Immunohistochemistry documentation of absence of LEKTI in the skin or confirmed SPINK5 gene mutations
• NS involvement of ≥20% of Body Surface Area (BSA)
• Patients must give written informed consent to participation in the study prior to Screening
• Participants must be willing and able to understand and comply with study requirements
• Participants must be willing to have skin tape harvests collected from lesional and nonlesional skin areas

You may not qualify if:

• Any skin disease that may interfere with the diagnosis or evaluation of NS
• Any infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before Screening visit
• Concomitant systemic disease not controlled by treatment. Stability for 3 months prior to Screening is required
• Kidney or liver disease with significant impairment of organ function (creatinine clearance \<30 mL/min, calculated using the Cockcroft-Gault Equation, and Child-Pugh Class C; ALT and AST \>2 × ULN range; total bilirubin \>1 × ULN).
• Concomitant disease or condition that may interfere with, or treatment of which may interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study
• Any significant condition (eg, medical, psychiatric, or social) that according to Investigator's judgment would prevent compliance with study protocol and full study participation
• Known hypersensitivity to any ingredient of the study drug product
• Anticipation of the need for surgery or hospitalization during the study
• History of suicide attempt or suicidal ideation within 1 year prior to Screening
• History of substance abuse within 6 months prior to Screening or a positive urine drug test at Screening. Medical marijuana may be used per discretion of the Investigator
• History or positive test result for human immunodeficiency virus (HIV) at Screening
• Active hepatitis B virus (HBV) infection, determined by positive test result for hepatitis B surface antigen, at Screening
• Active hepatitis C virus (HCV) infection, determined as HCV ribonucleic acid (RNA) above the limit of detection in patients with positive HCV antibody titer, at Screening
• Use of topical drugs that may alter the course of NS (eg, topical corticosteroids and topical calcineurin inhibitors) within 2 weeks before Screening or anticipation of need to use these drugs during study drug
• Systemic treatment with corticosteroids, immunosuppressants, targeted therapeutics, biologics, and IV Ig within 8 weeks before Screening

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

Saint Louis Hospital

Paris, 75012, France

Location

MeSH Terms

Conditions

Netherton Syndrome

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: September 28, 2023
• Primary Completion: January 6, 2025
• Study Completion: January 6, 2025
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

FR (1)