A Study to Evaluate Topically Applied SXR1096 Cream in Patients With Netherton Syndrome

Inclusion Criteria:

1. Male or female patients aged 18 to 65 years at the screening visit and alsoadolescents (12-17 years) only after initial cohort of 5 adult patients have beentreated 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 clinicalcriteria;
4. Neonatal erythroderma
5. Bamboo hair and/or alopecia
6. Chronic atopy specified as food allergy, asthma, rhino conjunctivitis and/oreczema for at least 2 years
7. Ichthyosis linearis circumflexa
8. Patients must be willing and able to understand and can comply with studyrequirements, apply the medication as instructed and be able to complete the study.
9. Absent LEKTI on immunohistochemistry of skin biopsy and/or confirmed mutation inSPINK5 gene
10. NS involvement ≥ 20% of Body Surface Area (BSA) required at both the screening andbaseline visits.
11. 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.
12. Female of childbearing potential must either commit true abstinence when this is inline with the preferred and usual lifestyle or use an adequate and approved method ofcontraception throughout the study and for 4 weeks after the last study drugapplication. This criterion also applies to a prepubertal female subject who beginsmenses during the study. Adequate and approved methods of contraception applicable for the subject and/or herpartner 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 transdermalhormonal 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 monthsbefore 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 medicalreason
• Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3months before screening

Exclusion Criteria:

1. Female patient who is pregnant, nursing an infant or planning a pregnancy throughoutthe course of the study
2. Patient with any uncontrolled systemic disease. A potential patient in whom therapyfor a systemic disease is not yet stabile for at least 3 months will not be consideredfor 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 orevaluation of the test medications. Cutaneous infection within 1 week before thebaseline visit or, any infection requiring treatment with oral or parenteralantibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before thebaseline visit.
5. Patient that has a condition or is in a situation, which in the investigator's opinionmay put the patient at significant risk, may confound the study results, or mayinterfere significantly with the patient's participation in the study.
6. Use of topical drugs that might alter the course of NS (e.g., topical corticosteroidsand topical calcineurin inhibitors) within two weeks before baseline visit.
7. Patient with a known sensitivity to any of the study treatments and/or theircomponents.
8. Patient who anticipates a need to use other topical or systemic therapy that mightalter the course of NS. Emollients/creams can be used on remaining skin area but notthe test areas. Use of topical prescription treatment within 2 weeks prior to initialdosing of study drug. Recent systemic treatment for NS (e.g. systemic corticosteroids,antibiotics, immunosuppressant, biologic and biosimilars treatments). A washout periodof 4 weeks will be required for such patients to be eligible to participate in thetrial.
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 aninvestigational drug or device, or participation in a clinical study within 30 daysprior to entering the study.
11. Suspected or confirmed COVID-19 infection within 4 weeks before the screening orbaseline visit. Unresolved COVID-19 infection. Planned vaccination for COVID-19 duringscreening, treatment period or before the follow-up visit.