Netherton Syndrome
Conditions
Keywords
Netherton Syndrome, DS-2325a
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.
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).
Interventions
DRUGDS-2325a
Main Phase and Extension Phase: Loading IV dose followed by maintenance SC doses
OTHERPlacebo
Main Phase: IV infusion followed by SC doses
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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: * 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameter Trough Concentration (Ctrough) - Main Phase | Main Phase: Week 1, 1 hour postdose, 2 hour postdose and Predose at Weeks 3, 5, 7, 9, and 11 | The Ctrough summaries include trough concentrations at the designed pre-dose time points that received a prior planned dose. |
| Pharmacokinetic Parameter Trough Concentration (Ctrough) - Extension Phase | Extension Phase: Predose at Weeks 13, 15, 17, 19, 21, and 23 | The Ctrough summaries include trough concentrations at the designed pre-dose time points that received a prior planned dose. |
| Median Change From Baseline in Ichthyosis Area Severity Index (IASI) Scores | Baseline up to Week 13 | 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. |
| Median Change From Baseline in Investigator Global Assessment (IGA) Scores | Baseline up to Week 13 | 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. |
| Median Change From Baseline in Itch Numerical Rating Scale (NRS) Scores | Baseline up to Week 13 | 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. |
| Median Change From Baseline in Skindex-29 Responses | Baseline up to Week 13 | 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. |
| Median Change From Baseline in Dermatology Life Quality Index (DLQI) Questionnaire Score | Baseline up to Week 13 | 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. |
| Number of Participants With Anti-Drug Antibodies Against DS-2325a (Interventional Part Main and Extension Phases) | Baseline up to Week 45 (end of study) | The anti-drug antibodies (ADAs) against DS-2325a was assessed as the immunogenicity endpoint. |
Countries
France
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
Participant flow
Recruitment details
A total of 9 participants were enrolled in the study and randomized to treatment at 1 clinic site in France.
Pre-assignment details
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29 years |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 1 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 2 / 5 | 2 / 4 | 5 / 5 | 4 / 4 | 4 / 5 | 2 / 3 |
| serious Total, serious adverse events | 0 / 5 | 1 / 4 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 3 |
Outcome results
None listed