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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-502853-32-00 | Other Identifier | EU CTR |
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The study was terminated based on a business decision by the Sponsor.
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DS-2325a | Drug | Main Phase and Extension Phase: Loading IV dose followed by maintenance SC doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Screening (Day 0) up to Week 45 (end of study) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
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
Participants must be willing to have skin tape harvests collected from lesional and nonlesional skin areas
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Global Clinical Leader | Daiichi Sankyo | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Saint Louis Hospital | Paris | 75012 | France |
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/
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.
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.
Study eligibility will be assessed at the beginning of the Observational Part and randomization for treatment will be done at the beginning of the Interventional Part, when eligibility will be re-confirmed.
A total of 9 participants were enrolled in the study and randomized to treatment at 1 clinic site in France.
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| ID | Title | Description |
|---|---|---|
| FG000 | DS-2325a | Participants were randomized to a single initial ("loading") dose of DS-2325a (Week 1) followed by ("maintenance") doses for a total of 12 weeks (Main Phase). Participants then received DS-2325a doses for a total of 24 weeks (Extension Phase). |
| FG001 | Placebo | Participants were randomized to a single initial ("loading") dose of Placebo (Week 1) followed by ("maintenance") doses for a total of 12 weeks (Main Phase). Participants then received DS-2325a doses for a total of 24 weeks (Extension Phase). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Interventional Part Main (12 Wks) |
|
| ||||||||||||||||||
| Interventional Part Extension (24 Wks) |
|
Baseline demographic characteristics were assessed in the Safety Analysis Set.
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| ID | Title | Description |
|---|---|---|
| BG000 | DS-2325a | Participants were randomized to a single initial ("loading") dose of DS-2325a (Week 1) followed by ("maintenance") doses for a total of 12 weeks (Main Phase). Participants then received DS-2325a doses for a total of 24 weeks (Extension Phase). |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Adverse events were assessed in the Safety Analysis Set. | Posted | Count of Participants | Participants | Screening (Day 0) up to Week 45 (end of study) |
|
Adverse events were collected from screening (Day 0) up to Week 45 (end of study).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DS-2325a (Observational Part) | Participants were assessed for 12 weeks preceding study treatment administration to establish a baseline for safety and efficacy endpoints. This group was randomized to treatment with DS-2325a at the start of the Interventional Part Main Phase. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nosocomial infection | Infections and infestations | MedDRA27.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA27.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daiichi Sankyo Contact for Clinical Trial Information | Daiichi Sankyo | 908-992-6400 | CTRinfo_us@daiichisankyo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 22, 2024 | Jan 6, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D056770 | Netherton Syndrome |
| ID | Term |
|---|---|
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016113 | Ichthyosiform Erythroderma, Congenital |
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| Placebo | Other | Main Phase: IV infusion followed by SC doses |
|
The Ctrough summaries include trough concentrations at the designed pre-dose time points that received a prior planned dose. |
| 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. | 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. | 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. | 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. | 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. | 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. | Baseline up to Week 45 (end of study) |
| NOT COMPLETED |
|
|
Participants were randomized to a single initial ("loading") dose of Placebo (Week 1) followed by ("maintenance") doses for a total of 12 weeks (Main Phase). Participants then received DS-2325a doses for a total of 24 weeks (Extension Phase). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Placebo (Observational Part) |
Participants were assessed for 12 weeks preceding study treatment administration to establish a baseline for safety and efficacy endpoints. This group was randomized to treatment with Placebo at the start of the Interventional Part Main Phase. |
| OG002 | DS-2325a (Interventional Part Main Phase) | Participants were randomized to a single initial ("loading") dose of DS-2325a (Week 1) followed by ("maintenance") doses for a total of 12 weeks. |
| OG003 | Placebo (Interventional Part Main Phase) | Participants were randomized to a single initial ("loading") dose of Placebo (Week 1) followed by ("maintenance") doses for a total of 12 weeks. |
| OG004 | DS-2325a (Interventional Part Extension Phase) | Participants received DS-2325a doses for a total of 24 weeks. This group was randomized to treatment with DS-2325a at the start of the Interventional Part Main Phase. |
| OG005 | Placebo (Interventional Part Extension Phase) | Participants received DS-2325a doses for a total of 24 weeks. This group was randomized to treatment with Placebo at the start of the Interventional Part Main Phase. |
|
|
| Secondary | 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. | Participants received different frequencies of doses (changing from weekly to biweekly from Week 5 after protocol amendment) and different numbers of doses due to early study termination. The Ctrough summaries excluded one participant who received weekly dosing instead of biweekly dosing through Week 11. | Posted | Mean | Standard Deviation | ng/mL | Main Phase: Week 1, 1 hour postdose, 2 hour postdose and Predose at Weeks 3, 5, 7, 9, and 11 |
|
|
|
| Secondary | 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. | Participants received different frequencies of doses (changing from weekly to biweekly from Week 5 after protocol amendment) and different numbers of doses due to early study termination. The Ctrough summaries excluded one participant who received weekly dosing instead of biweekly dosing through Week 11. | Posted | Mean | Standard Deviation | ng/mL | Extension Phase: Predose at Weeks 13, 15, 17, 19, 21, and 23 |
|
|
|
| Secondary | 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. | The IASI score was assessed in participants with available data in the Modified Intent-to-Treat Analysis Set. | Posted | Median | Full Range | score on a scale | Baseline up to Week 13 |
|
|
|
| Secondary | 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. | The IGA scores were accessed in participants with available data in the Modified Intent-to-Treat Analysis Set. | Posted | Median | Full Range | score on a scale | Baseline up to Week 13 |
|
|
|
| Secondary | 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. | The Itch NRS scores were accessed in participants with available data in the Modified Intent-to-Treat Analysis Set. | Posted | Median | Full Range | score on a scale | Baseline up to Week 13 |
|
|
|
| Secondary | 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. | Skindex-29 responses were assessed in participants with available data in the Modified Intent-to-Treat Analysis Set. | Posted | Median | Full Range | score on a scale | Baseline up to Week 13 |
|
|
|
| Secondary | 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. | Dermatology Life Quality Index Questionnaire was assessed in participants with available data in the Modified Intent-to-Treat Analysis Set. | Posted | Median | Full Range | score on a scale | Baseline up to Week 13 |
|
|
|
| Secondary | 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. | ADA's were assessed in participants with available data in the Pharmacokinetic Analysis Set. | Posted | Count of Participants | Participants | Baseline up to Week 45 (end of study) |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Placebo (Observational Part) | Participants were assessed for 12 weeks preceding study treatment administration to establish a baseline for safety and efficacy endpoints. This group was randomized to treatment with Placebo at the start of the Interventional Part Main Phase. | 0 | 4 | 1 | 4 | 2 | 4 |
| EG002 | DS-2325a (Interventional Part Main Phase) | Participants were randomized to a single initial ("loading") dose of DS-2325a (Week 1) followed by ("maintenance") doses for a total of 12 weeks. | 0 | 5 | 0 | 5 | 5 | 5 |
| EG003 | Placebo (Interventional Part Main Phase) | Participants were randomized to a single ("initial") loading dose of Placebo (Week 1) followed by ("maintenance") doses for a total of 12 weeks. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG004 | DS-2325a (Interventional Part Extension Phase) | Participants received DS-2325a doses for a total of 24 weeks. This group was randomized to treatment with DS-2325a at the start of the Interventional Part Main Phase. | 0 | 5 | 0 | 5 | 4 | 5 |
| EG005 | Placebo (Interventional Part Extension Phase) | Participants received DS-2325a doses for a total of 24 weeks. This group was randomized to treatment with Placebo at the start of the Interventional Part Main Phase. | 0 | 3 | 0 | 3 | 2 | 3 |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA27.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Nosocomial infection | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Proteus infection | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Extrasystoles | Cardiac disorders | MedDRA27.1 | Systematic Assessment |
|
| Netherton's syndrome | Congenital, familial and genetic disorders | MedDRA27.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA27.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA27.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA27.1 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA27.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA27.1 | Systematic Assessment |
|
| Influenza-like illness | General disorders | MedDRA27.1 | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA27.1 | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA27.1 | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA27.1 | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA27.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA27.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA27.1 | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Viral rhinitis | Infections and infestations | MedDRA27.1 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA27.1 | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | MedDRA27.1 | Systematic Assessment |
|
| Food allergy | Immune system disorders | MedDRA27.1 | Systematic Assessment |
|
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| D007057 | Ichthyosis |
| D012868 | Skin Abnormalities |
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D007232 | Infant, Newborn, Diseases |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Title | Measurements |
|---|---|
|
| Week 5 (predose) |
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| Week 7 (predose) |
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| Week 9 (predose) |
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| Week 11 (predose) |
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| Week 17 (predose) |
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| Week 19 (predose) |
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| Week 21 (predose) |
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| Week 23 (predose) |
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| Inflammatory papules or plaques |
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| Oozing |
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| Lichenification |
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| Functioning Score |
|