Netherton SyndromePhase 1/2NCT05979831
A Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome
A Phase 1/2 study testing DS-2325a in people with Netherton Syndrome, run by Daiichi Sankyo at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Netherton Syndrome
- What is being tested?
- DS-2325a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteFrance
- Study dates
- 28 Sep 2023to 6 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
- Participation in any other clinical study or expanded access program with an investigational drug or device within 4 weeks before Screening
- Suspected or confirmed COVID-19 within 4 weeks before or ongoing at Screening and planned vaccination against COVID-19 during study drug
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1b/2, Double-Blind, Placebo-Controlled, Randomized, Parallel-Arm Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome
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.
Read the detailed description
This study will explore the safety, pharmacokinetics (PK), and early clinical signal efficacy of DS-2325a in adult patients with NS. The primary objective of the study will be to explore the safety and tolerability of DS-2325a in patients with NS by administering DS-2325a for 12 consecutive weeks (Main Phase, which will be double-blind and during which some participants will receive placebo as a control) and to confirm by administering for an additional 24 weeks (Extension Phase, which will be open-label and during which all participants will receive DS-2325a). Secondary objectives of the study will include exploring the PK properties, efficacy, and immunogenicity of DS-2325a in patients with NS by administering DS-2325a for 12 consecutive weeks (Main Phase) and to confirm by administering for an additional 24 weeks (Extension Phase).
- Conditions
- Netherton Syndrome
- Being tested
- DS-2325a, Placebo
- Keywords
- Netherton Syndrome, DS-2325a
- Medical subject headings
- Netherton Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-2325aDrug
Main Phase and Extension Phase: Loading IV dose followed by maintenance SC doses
PlaceboOther
Main Phase: IV infusion followed by SC doses
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) v 27.1.
Measured: Screening (Day 0) up to Week 45 (end of study)
Secondary outcomes (8)
Pharmacokinetic Parameter Trough Concentration (Ctrough) - Main Phase
The Ctrough summaries include trough concentrations at the designed pre-dose time points that received a prior planned dose.
Measured: Main Phase: Week 1, 1 hour postdose, 2 hour postdose and Predose at Weeks 3, 5, 7, 9, and 11
Pharmacokinetic Parameter Trough Concentration (Ctrough) - Extension Phase
The Ctrough summaries include trough concentrations at the designed pre-dose time points that received a prior planned dose.
Measured: Extension Phase: Predose at Weeks 13, 15, 17, 19, 21, and 23
Median Change From Baseline in Ichthyosis Area Severity Index (IASI) Scores
The IASI assesses the intensity of the participant's erythema (IASI-Erythema) and scaling (IASI-Scaling) using a 4-point Likert scale ranging from 0 (none) to 4 (very severe). The total IASI (range 0 to 48) is determined by adding IASI-Erythema and IASI-Scaling scores. Higher scores indicate worse clinical outcome. A change from baseline is being reported and the greater the change the worse clinical outcome.
Measured: Baseline up to Week 13
Median Change From Baseline in Investigator Global Assessment (IGA) Scores
The IGA assesses a participant's erythema, scaling, inflammatory papules or plaques, oozing, and lichenification using a 5-point scale (0, clear; 1, almost clear; 2, mild; 3, moderate; 4, severe). Higher scores indicate worse clinical outcome. The change from baseline is being reported where negative values indicate an improvement in clinical outcome.
Measured: Baseline up to Week 13
Median Change From Baseline in Itch Numerical Rating Scale (NRS) Scores
The Itch NRS is a self-rated single item scale designed for assessing worst pruritus in the past 7 days. The scale utilizes an 11-point NRS, scored from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicate worse clinical outcome. The change from baseline is being reported with negative values indicating an improvement in clinical outcome.
Measured: Baseline up to Week 13
Median Change From Baseline in Skindex-29 Responses
The Skindex-29 is a 29-item questionnaire that assesses the burden of the participant's skin condition on 3 scales - symptoms, social functioning and emotional well-being. The score for each scale ranges from 0 to 100. Higher scores reflect a worse quality of life.
Measured: Baseline up to Week 13
Median Change From Baseline in Dermatology Life Quality Index (DLQI) Questionnaire Score
The Dermatology Life Quality Index (DLQI) is a 10-item validated questionnaire used to assess participants' perception of the impact of their skin disease on different aspects of their quality of life over the prior week. The DLQI score is the sum of the 10 item scores and ranges from 0 to 30. A high score is indicative of a poor quality of life.
Measured: Baseline up to Week 13
Number of Participants With Anti-Drug Antibodies Against DS-2325a (Interventional Part Main and Extension Phases)
The anti-drug antibodies (ADAs) against DS-2325a was assessed as the immunogenicity endpoint.
Measured: Baseline up to Week 45 (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2023
- Study start28 Sep 2023
- Primary completion6 Jan 2025
- Study completion6 Jan 2025
Why it stopped: The study was terminated based on a business decision by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Netherton SyndromeStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05979831
- Sponsor's protocol ID
- DS2325-119
- Other IDs
- 2022-502853-32-00
- Status last verified
- Apr 2026
- First submitted
- 31 Jul 2023
- Last updated
- 14 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2, Double-Blind, Placebo-Controlled, Randomized, Parallel-Arm Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome
- ClinicalTrials.gov ID
- NCT05979831
- Acronym / sponsor ID
- DS2325-119
- Conditions
- Netherton Syndrome
- Keywords
- Netherton Syndrome, DS-2325a
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated based on a business decision by the Sponsor.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2023 (actual)
- Primary completion
- 6 Jan 2025 (actual)
- Study completion
- 6 Jan 2025 (actual)
- First posted
- 7 Aug 2023 (actual)
- Results
- Posted 14 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will explore the safety, pharmacokinetics (PK), and early clinical signal efficacy of DS-2325a in adult patients with NS. The primary objective of the study will be to explore the safety and tolerability of DS-2325a in patients with NS by administering DS-2325a for 12 consecutive weeks (Main Phase, which will be double-blind and during which some participants will receive placebo as a control) and to confirm by administering for an additional 24 weeks (Extension Phase, which will be open-label and during which all participants will receive DS-2325a). Secondary objectives of the study will include exploring the PK properties, efficacy, and immunogenicity of DS-2325a in patients with NS by administering DS-2325a for 12 consecutive weeks (Main Phase) and to confirm by administering for an additional 24 weeks (Extension Phase).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DS-2325a | Experimental | Drug: DS-2325aParticipants 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). |
| Placebo | Placebo comparator | Other: PlaceboParticipants 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-2325aMain Phase and Extension Phase: Loading IV dose followed by maintenance SC doses | Drug | DS-2325a |
| PlaceboMain Phase: IV infusion followed by SC doses | Other | Placebo |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events
Time frame: Screening (Day 0) up to Week 45 (end of study)
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) v 27.1.
8 secondary outcomes
Pharmacokinetic Parameter Trough Concentration (Ctrough) - Main Phase
Time frame: Main Phase: Week 1, 1 hour postdose, 2 hour postdose and Predose at Weeks 3, 5, 7, 9, and 11
Pharmacokinetic Parameter Trough Concentration (Ctrough) - Extension Phase
Time frame: Extension Phase: Predose at Weeks 13, 15, 17, 19, 21, and 23
Median Change From Baseline in Ichthyosis Area Severity Index (IASI) Scores
Time frame: Baseline up to Week 13
Median Change From Baseline in Investigator Global Assessment (IGA) Scores
Time frame: Baseline up to Week 13
Median Change From Baseline in Itch Numerical Rating Scale (NRS) Scores
Time frame: Baseline up to Week 13
Median Change From Baseline in Skindex-29 Responses
Time frame: Baseline up to Week 13
Median Change From Baseline in Dermatology Life Quality Index (DLQI) Questionnaire Score
Time frame: Baseline up to Week 13
Number of Participants With Anti-Drug Antibodies Against DS-2325a (Interventional Part Main and Extension Phases)
Time frame: Baseline up to Week 45 (end of study)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DS-2325a in people with Netherton Syndrome, run by Daiichi Sankyo at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (time frame: Screening (Day 0) up to Week 45 (end of study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026; AzTrials last refreshed its copy on 7 Nov 2026.