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

NCT05211830 | Completed Phase 1 DMC

• 1 other identifier: SXR001
• Study Type: interventional
• Target: 9
• Locations: 4 countries
• Sites: 5

Brief Summary

In this phase I/II trial a topical skin cream with the active substance SXR1096 will be tested in patients with Netherton syndroms, a rare inflammatory skin disease. SXR1096 is a specific and potent protease inhibitor that can inhibit the proteases kallikrein 5, 7 and 14 - all recognised as up-regulated and causing the disease state in Netherton syndrome patients. Patients will be treated for one month with active cream and placebo cream at different areas of the skin.

Conditions

Netherton Syndrome

Outcome Measures

Primary Outcomes (3)

• Safety of the treatment with SXR1096 compared to placebo in initial cohort of adults

  Number of patients with treatment-related adverse events during the treatment period of 4 weeks

  4 week

• Safety of the treatment with SXR1096 compared to placebo in adults and adolescents

  Number of patients with treatment-related adverse events during the treatment period of 4 weeks

  4 weeks

• Efficacy of the treatment with SXR1096 compared to placebo in adults and adolescents

  The change in Investigator Global Assessment (IGA) score 0-4 at EOT compared to baseline (0 being clear of lesions (erythema and scaling) and 4 being the worst score).

  4 weeks

Study Arms (2)

SXR1096 cream

EXPERIMENTAL

The active treatment will be the specific small molecule inhibitor of KLK5, 7 and 14 in a proprietary skin cream formulation.

Drug: SXR1096 cream

Placebo cream

PLACEBO COMPARATOR

The placebo control will be the proprietary skin cream formulation without the active substance.

Drug: Placebo cream

Interventions

SXR1096 cream DRUG

Skin cream to be applied twice a day to a predefined area of the skin

SXR1096 cream

Placebo cream DRUG

Skin cream to be applied twice a day to a predefined area of the skin

Placebo cream

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients/legal guardian endpoint must be willing to provide written informed consent.
• 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, asthma, rhino conjunctivitis and/or eczema for at least 2 years
• Ichthyosis linearis circumflexa
• 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.
• Absent LEKTI on immunohistochemistry of skin biopsy and/or confirmed mutation in SPINK5 gene
• NS involvement ≥ 20% of Body Surface Area (BSA) required at both the screening and baseline visits.
• 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.
• 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)

You may not qualify if:

• Female patient who is pregnant, nursing an infant or planning a pregnancy throughout the course of the study
• 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.
• Patient with positive serology tests like HIV, HCV \& HBsAg.
• 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.
• 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.
• 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.
• Patient with a known sensitivity to any of the study treatments and/or their components.
• 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.
• Patient who anticipates the need for surgery or hospitalization during the study.
• 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.
• 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.

Sponsors & Collaborators

• Sixera Pharma: lead

Study Sites (5)

Medical University Innsbruck, Tirol Kliniken

Innsbruck, Austria

Location

Saint Louis Hospital

Paris, 75010, France

Location

Necker Hospital

Paris, France

Location

University of Freiburg

Freiburg im Breisgau, Germany

Location

Karolinska Hospital, Huddinge

Stockholm, Sweden

Location

MeSH Terms

Conditions

Netherton Syndrome

Condition Hierarchy (Ancestors)

Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Maarten de Chateau, MD PhD

  Sixera Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active and placebo will be provided in a blinded fashion.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will act as their own controls as they will all be treating different contralateral areas of the skin with active and placebo creams in a blinded fashion.

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: January 27, 2022
• Study Start: December 7, 2021
• Primary Completion: June 10, 2025
• Study Completion: August 20, 2025
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); FR (2); SE (1); AU (1)