Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ended
Participants planned
12
Countries
1
Sites
1
Netherton's Syndrome
The primary objective of this study is to explore the safety and tolerability of DS-2325a in patients with NS.
Key facts
- Sponsor
- Daiichi Sankyo Inc.
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 18 Aug 2023 → 7 Jan 2025
- Decision date (initial)
- 2023-07-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2022-502853-32-00
- ClinicalTrials.gov
- NCT05979831
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic
The primary objective of this study is to explore the safety and tolerability of DS-2325a in patients with NS.
Secondary objectives 4
- Secondary Objective: To explore the pharmacokinetic (PK) properties of DS-2325a in patients with NS.
- Secondary Objective: To explore the efficacy of DS-2325a in patients with NS.
- Secondary Objective: To explore the immunogenicity of DS-2325a in patients with NS.
- Observational Part Objective: To explore the characteristics of patients with NS for 12 weeks immediately before study treatment administration by assessing the same safety and efficacy (including mechanistic efficacy) endpoints to be assessed during the Interventional Part.
Conditions and MedDRA coding
Netherton's Syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10062909 | Netherton's syndrome | 100000004850 |
Study design 4 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Observational Part Observational Part will last for 12 weeks, during which patients will not be treated and will be investigated only to understand the course of their disease.
The intent of the Observational Part of the study is to gather ample information on the course of the NS disease of each patient participating in the study during the time immediately preceding study treatment administration.
During the Observational Part, patients will be assessed according to the same safety and efficacy (including mechanistic efficacy) endpoints, as
the Interventional Part Main Phase. This should give stronger possibility of comparing posttreatment with pre-treatment data than simply assessing patients once at Baseline, enhancing therefore the possibility to conclude if DS-2325a gives early clinical signal or not. Additionally, the information collected during Observational Part will possibly be used to elaborate a mathematical disease progression model that could also facilitate concluding if DS-2325a gives early clinical signal or not. Participation in the Observational Part should also give patients the possibility of acclimatizing with study environment and familiarizing with study procedures, such as use of questionnaires.
|
Not Applicable | None | ||
| 2 | Interventional Part Main Phase The Interventional Part Main Phase will be 12 week, double-blinded and placebo-controlled part, where patients will be randomized to 2 parallel arms to receive DS-2325a or placebo in a 2:1 ratio.
The intent of the Interventional Part of the study is to explore DS-2325a safety and efficacy, by comparing post-treatment with pre-treatment NS course and, in the Main Phase, the effect on NS of treatment with DS-2325a with treatment with placebo. Double-blind, placebo-controlled, and randomized design of the Interventional Part Main Phase should minimize bias. In addition to characterizing safety, intent of the Interventional Part Main Phase is to find early clinical signal, as initial evidence of DS-2325a efficacy.
|
Randomised Controlled | Double | [{"id":80149,"code":1,"name":"Subject"},{"id":80148,"code":3,"name":"Monitor"},{"id":80151,"code":5,"name":"Carer"},{"id":80150,"code":2,"name":"Investigator"}] | DS-2325a: Arm involves patients receiving DS-2325a Placebo: Arm involves patients receiving placebo |
| 3 | Interventional Part Extension Phase The Extension Phase will last for 24 weeks, it will be open-label and all patients will receive DS-2325a SC.
All patients will transition from the Interventional Part Main Phase to the Extension Phase. The Extension Phase will be discontinued if early clinical signal is not found.
The intent of the Interventional Part Extension Phase is to gather additional safety and efficacy information on DS-2325a, albeit under open-label design.
|
2 | None | ||
| 4 | Follow-Up The intent of the Follow-Up component of the study is to monitor DS-2325a safety from the end of treatment, marked by the End of Treatment (EOT) visit, 1 week after the last drug administration, until the time DS-2325a is expected to have been virtually completely eliminated, marked by the End of Study (EOS) visit 8 weeks after EOT.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Male or female patients aged 18 to 65 years with clinical diagnosis of NS including at least 3 out of the 4 following clinical criteria: 1. Neonatal erythroderma; 2. Bamboo hair and/or alopecia; 3. Chronic atopy specified as food allergy and/or asthma and/or rhino-conjunctivitis and/or eczema for at least 2 years; 4. Ichthyosis linearis circumflexa or scaling erythroderma or equivalent. Eligible participants are those who have received treatment in the past that did not work and so need the further care.
- Immunohistochemistry documentation of absence of lympho-epithelial Kazal-type-related inhibitor (LEKTI) in the skin or confirmed serine peptidase inhibitor of Kazal type 5 (SPINK5) gene mutations.
- NS involvement of ≥20% of Body Surface Area (BSA) at both Screening and Baseline.
- Patients must give written informed consent to participation in the study prior to Screening.
- Patients must be willing to have skin tape harvests collected from lesional and non-lesional skin areas
Exclusion criteria 2
- 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.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Safety endpoints will be adverse events (AEs), including serious AEs (SAEs), injection site reactions (ISRs), physical examination findings, vital sign recordings (body temperature, blood pressure, heart rate, respiratory rate), results of safety laboratory analyses of blood and urine, and electrocardiogram (ECG) findings.
Secondary endpoints 4
- Endpoints descriptive of plasma PK properties will be PK parameters derived from population PK analysis, including, but not limited to, pre-dose trough concentration (Ctrough), AUCtau,ss, total body clearance (CL), and CL/F, and epidermis-to-dermis DS-2325a concentration ratio (Ked).
- DS-2325a presence will be assessed in the skin if the optional skin biopsies will be available.
- Several endpoints for the assessment of efficacy (ECS), including, but not limited to IASI (including IASI-Erythema and IASI Scaling), Investigator Global Assessment (IGA) and patient-reported outcome (PRO) measures, such as Itch Numerical Rating Scale (NRS) scores and quality-of-life assessments obtained using the Skindex-29 and the Dermatology-Life-Quality-Index (DLQI) questionnaires.
- Anti-drug antibodies (ADAs) against DS-2325a will be the immunogenicity endpoint.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10210888 · Product
- Active substance
- DS-2325A
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- SUBCUTANEOUS OR INTRAVENOUS
- Authorisation status
- Not Authorised
- MA holder
- DAIICHI SANKYO, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
SUB20079 · Substance
- Active substance
- Sodium Chloride Solution 0.9%
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Daiichi Sankyo Inc.
- Sponsor organisation
- Daiichi Sankyo Inc.
- Address
- 211 Mount Airy Road
- City
- Basking Ridge
- Postcode
- 07920-2311
- Country
- United States
Scientific contact point
- Organisation
- Daiichi Sankyo Inc.
- Contact name
- Clinical Trial Office
Public contact point
- Organisation
- Daiichi Sankyo Inc.
- Contact name
- Clinical Trial Office
Third parties 10
| Organisation | City, country | Duties |
|---|---|---|
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Laboratory analysis |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Invicro LLC ORG-100046990
|
Boston, United States | Laboratory analysis |
| WCG Clinical Inc. ORG-100040730
|
Los Angeles, United States | Other |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Laboratory analysis |
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Laboratory analysis |
| Imagine Institut Des Maladies Genetiques Necker Enfants Malades ORG-100013367
|
Paris, France | Laboratory analysis |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Greenfield, United States | Laboratory analysis |
| Labcorp Central Laboratory Services S.a.r.l. Meyrin ORG-100011524
|
Meyrin, Switzerland | Laboratory analysis |
| Iqvia Limited ORG-100008655
|
Reading, United Kingdom | On site monitoring, Code 10, Code 11, Code 12, Code 2, Code 5, Data management, Code 8 |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 12 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2023-08-18 | 2023-09-28 | 2024-09-10 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-64556
- Halt date
- 2024-09-10
- Member states concerned
- France
- Publication date
- 2024-12-20
- Reason
- Sponsor decision, Medicinal Product related
- Explanation
- Refer to the attached document
- Follow-up measures
- Refer to the attached document
- Benefit-risk balance changed
- No
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| DS2325-119 Summary of Results SUM-113533
|
2026-01-06T20:37:12 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| DS2325-119 Lay Person Summary of Results | 2026-01-06T20:37:50 | Submitted | Laypersons Summary of Results |
Documents 18 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | DS2325-119 PLS Final Draft 19 Dec 2025 | 1 |
| Protocol (for publication) | D1_Protocol_2022-502853-32-00_red_san | 3.0 |
| Protocol (for publication) | D1_Protocol_Pharmacy_Manual_2022-502853-32-00_red_san | 1 |
| Protocol (for publication) | D4_Patient Facing Document_Patient_ID_Card_FR_san | 2.0 |
| Protocol (for publication) | D4_Patient Facing Document_PRO_DLQI_FR_san | N/A |
| Protocol (for publication) | D4_Patient Facing Document_PRO_Itch NRS_2022-502853-32-00_FR_san | 2 |
| Protocol (for publication) | D4_Patient Facing Document_PRO_Skindex29_2022-502853-32-00_FR_san | N/A |
| Recruitment arrangements (for publication) | K_2022-502853-32_Recruitment and Consent_FR_san | 1 |
| Subject information and informed consent form (for publication) | 2022-502853-32_Pr HOVNANIAN Letter_Red-San | NA |
| Subject information and informed consent form (for publication) | L_1_2022-502853-32_Informed Consent Form_Patient_FRA_san | V2.0FRA1.0 |
| Subject information and informed consent form (for publication) | L_2_2022-502853-32_Informed Consent Form_Pregnant Partner_FR_san | V1.0FRA2.0 |
| Subject information and informed consent form (for publication) | L3_2022-502853-32_Welcome Letter_FRA_San | V1.0 |
| Subject information and informed consent form (for publication) | L4_2022-502853-32_Payment Card Letter_FRA_San | V1.0 |
| Subject information and informed consent form (for publication) | L5_2022-502853-32_Expense Claim Form_FRA_San | 2.0 |
| Subject information and informed consent form (for publication) | L6_2022-502853-32_Personal Data Consent Form_FRA_San | V1.0 |
| Summary of results (for publication) | DS2325-119 EU CTIS Draft 05Jan2026 | 1 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_EN_2022-502853-32-00_san | 3.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_FR_2022-502853-32-00_san | 3.0 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-31 | France | Acceptable 2023-07-10
|
2023-07-17 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-11-14 | France | Acceptable | 2024-01-19 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-02-19 | France | Acceptable 2024-03-29
|
2024-03-29 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-07-17 | France | Acceptable | 2024-08-13 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-10-15 | France | Acceptable | 2024-10-15 |