E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Netherton-syndrome |
Nethertonin oireyhtymä |
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E.1.1.1 | Medical condition in easily understood language |
Netherton-syndrome |
Nethertonin oireyhtymä |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062909 |
E.1.2 | Term | Netherton's syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate clinical safety and efficacy of the treatment with the IMP, compared to placebo, in patients with NS. |
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E.2.2 | Secondary objectives of the trial |
Scondary objectives: •Skin itching during the treatment period will be assessed by VAS and a multidimensional 5- D pruritus scale (Phan et al. 2012). •Skin surface pH and transepidermal water loss (TEWL) will be compared at baseline and EOT. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 18 to 65 years at the screening visit and also adolescents (12-17 years) only after initial cohort of 5 adult patients have been treated for at least three days. 2. Patients/legal guardian endpoint must be willing to provide written informed consent. 3. Clinical diagnosis of NS including at least 3 out of the 4 following clinical criteria; a. Neonatal erythroderma b. Bamboo hair and/or alopecia c. Chronic atopy specified as food allergy, asthma, rhino conjunctivitis and/or eczema for at least 2 years d. Ichthyosis linearis circumflexa 4. Patients must be willing and able to understand and can comply with study requirements, apply the medication as instructed and be able to complete the study. 5. Absent LEKTI on immunohistochemistry of skin biopsy and/or confirmed mutation in SPINK5 gene 6. NS involvement ≥ 20% of Body Surface Area (BSA) required at both the screening and baseline visits. 7. Investigator Global Assessment (IGA) of two areas to be treated, score ≥3, i.e. moderate or severe for each area required. Each target area approx. 9% of BSA. i.e. equal to one arm. 8. Female of childbearing potential must either commit true abstinence when this is in line with the preferred and usual lifestyle or use an adequate and approved method of contraception throughout the study and for 4 weeks after the last study drug application. This criterion also applies to a prepubertal female subject who begins menses during the study. Adequate and approved methods of contraception applicable for the subject and/or her partner are defined below: • Progestogen-only oral hormonal contraception • Combination of male or female condom with cap, diaphragm, or sponge with spermicide (double barrier methods) • Combined (estrogen- and progestogen-containing) oral, intravaginal, or transdermal hormonal contraception • Injectable or implanted hormonal contraception • Intrauterine devices or intrauterine hormone-releasing system • Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the study • Vasectomy of partner at least 3 months before the study • Female subjects of non-childbearing potential must meet one of the following criteria: • Absence of menstrual bleeding for 1 year prior to screening without any other medical reason • Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening |
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E.4 | Principal exclusion criteria |
1. Female patient who is pregnant, nursing an infant or planning a pregnancy throughout the course of the study 2. Patient with any uncontrolled systemic disease. A potential patient in whom therapy for a systemic disease is not yet stabile for at least 3 months will not be considered for entry into the study. 3. Patient with positive serology tests like HIV, HCV & HBsAg. 4. Patient with presence of any skin disease that might interfere with the diagnosis or evaluation of the test medications. Cutaneous infection within 1 week before the baseline visit or, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit. 5. Patient that has a condition or is in a situation, which in the investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study. 6. Use of topical drugs that might alter the course of NS (e.g., topical corticosteroids and topical calcineurin inhibitors) within two weeks before baseline visit. 7. Patient with a known sensitivity to any of the study treatments and/or their components. 8. Patient who anticipates a need to use other topical or systemic therapy that might alter the course of NS. Emollients/creams can be used on remaining skin area but not the test areas. Use of topical prescription treatment within 2 weeks prior to initial dosing of study drug. Recent systemic treatment for NS (e.g. systemic corticosteroids, antibiotics, immunosuppressant, biologic and biosimilars treatments). A washout period of 4 weeks will be required for such patients to be eligible to participate in the trial. 9. Patient who anticipates the need for surgery or hospitalization during the study. 10. Concurrent involvement in any other clinical study/expanded access program with an investigational drug or device, or participation in a clinical study within 30 days prior to entering the study. 11. Suspected or confirmed COVID-19 infection within 4 weeks before the screening or baseline visit. Unresolved COVID-19 infection. Planned vaccination for COVID-19 during screening, treatment period or before the follow-up visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints: • Safety assessment includes adverse events (nature and incidence), physical examination, vital signs, laboratory safety, and local tolerability. • Primary efficacy endpoint: o The change in Investigator Global Assessment (IGA) score 0-4 (see table in Appendix B) at EOT compared to baseline.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A) To assess the safety of SXR1096 multiple doses (3 days of treatment) in adults Part B) To assess the safety and efficacy of 4 weeks treatment with SXR1096 in adults and adolescents (12-17 years)
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: • The skin condition will be characterized primarily by Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); this score has been recently developed and validated by applying it to patients affected with NS (Paller et al., 2017). • Skin itching will be assessed by VAS and a multidimensional 5-D pruritus scale (Phan et al., 2012). • Skin surface pH and transepidermal water loss (TEWL) will be measured on treated areas. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part A) To assess the safety of SXR1096 multiple doses (3 days of treatment) in adults Part B) To assess the safety and efficacy of 4 weeks treatment with SXR1096 in adults and adolescents (12-17 years) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
split-body (placebo within patient) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |