Netherton SyndromePhase 1NCT06137157
Evaluation of Topical ATR12-351 in Adults With Netherton Syndrome
A Phase 1 study testing ATR12-351 in people with Netherton Syndrome, run by Azitra Inc. at 2 sites in United States.
Trial summary
The objectives of this clinical trial are to evaluate the safety and tolerability of topically applied ATR12-351, to understand what the body does to ATR12-351, and to observe treatment benefits of the drug in approximately 12 adult patients with Netherton Syndrome (NS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Netherton Syndrome
- What is being tested?
- ATR12-351
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Jun 2024to 7 Jul 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years of age
- Confirmed mutation of the serine protease inhibitor of Kazal type 5 (SPINK5) gene
- Involvement of ≥20% of body surface area with skin changes consistent with Netherton syndrome
Who cannot join
- Use of biologic therapies, antibiotics, antihistamines, corticosteroids, retinoids, disease-modifying antirheumatic drugs (DMARDs), immunosuppressive agents, phosphodiesterase-4 (PDE4) inhibitors, topical calcineurin inhibitors, or topical Janus kinase (JAK) inhibitors
- Open wounds or extensive areas of excoriation precluding identification of appropriate application sites in the Investigator's judgment
- Concurrent involvement in any other clinical study/expanded access program with an investigational drug or device or has participated in a clinical study within 30 days prior to the screening visit
- Residing with an immunocompromised person in the same dwelling from the baseline visit through 2 weeks after the treatment period
- History of ultraviolet phototherapy within the planned treatment area 4 weeks prior to baseline
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale University
New Haven, Connecticut, 06519
Stanford University
Palo Alto, California, 94304
About this study
Official title: A Randomized, Double-Blind, Vehicle-Controlled, First-in-Human Safety, Tolerability and Proof-of-Concept Study of Topical ATR12-351 in Adults With Netherton Syndrome
The objectives of this clinical trial are to evaluate the safety and tolerability of topically applied ATR12-351, to understand what the body does to ATR12-351, and to observe treatment benefits of the drug in approximately 12 adult patients with Netherton Syndrome (NS). ATR12-351 will be applied to skin lesions on one side of the body, while the vehicle control will be applied to similar lesion on the other side of the body twice daily for 2 weeks.
Read the detailed description
Netherton syndrome (NS) is a rare but severe autosomal recessive disease that affects the skin, hair, and immune system. NS presents at birth with red skin covered by fine scales, a specific hair shaft abnormality ("bamboo hair"), atopic lesions, and elevated systemic immunoglobulin E (IgE) levels. Patients often develop allergies and asthma, and the unfortunate prognosis for infants with NS is poor, with 10% mortality in the first 6 months of life and recurrent infections. There are no FDA-approved treatment options for NS. NS is caused by mutations in in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI). Absence of LEKTI causes unregulated activity of proteases in the kallikrein subfamily, causing excessive desquamation of skin.
ATR12-351 is a topical ointment containing a lyophilized version of a live biotherapeutic product (LBP), Staphylococcus epidermidis (SE) strain designated SE351. This strain has been modified to be auxotrophic and to express recombinant human LEKTI protein (rhLEKTI). ATR12-351 is intended to address the underlying cause of NS by replacing deficient/dysfunctional LEKTI. The treatment consists of applying ATR12-351 to affected areas, where rhLEKTI produced by ATR12-351 will counter the dysregulated skin serine protease activity observed in NS patients.
This first-in-human study is a randomized, double-blind, vehicle-controlled clinical study to assess the safety, tolerability, and pharmacokinetics (PK) of topical ATR12-351 in approximately 12 adult Netherton syndrome patients who will serve as their own control. This study will include a 14-day treatment period to investigate the safety and tolerability of ATR12-351 applied to the skin and will be followed a total of 84 days for safety. The results of this first-in-human clinical study will establish safety and tolerability as well as initial efficacy of ATR12-351 application in Netherton syndrome patients.
- Conditions
- Netherton Syndrome
- Being tested
- ATR12-351
- Keywords
- Ichthyosis, Netherton syndrome, Skin disease, ichthyosis linearis circumflexa
- Medical subject headings
- Netherton Syndrome, Ichthyosis, Skin Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATR12-351Drug
Also called ATR-12
Topical ointment containing ATR12-351, a LEKTI-secreting strain of S. epidermidis
| Study group | Role | What they receive |
|---|---|---|
| Internal controlled arm | Experimental | ATR12-351 on left side of body, vehicle on right side of body in one group; vehicle on left side of body, ATR12-351 on right side of body. Receives: Drug: ATR12-351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events
Measured: 84 days
Secondary outcomes (5)
Investigator's Global Assessment (IGA)
Visual assessment of the overall severity of skin disease severity at each application site, using a 5-point scale (0, clear; 1, almost clear/minimal; 2, mild; 3, moderate; 4, severe). Higher scores indicate greater severity.
Measured: 42 days
Patient's Global Assessment (PGA)
Visual assessment of the overall severity of skin disease severity at each application site, using a 5-point scale (0, clear; 1, almost clear/minimal; 2, mild; 3, moderate; 4, severe). Higher scores indicate greater severity.
Measured: 42 days
NS-modified SCORAD
The investigator's objective assessment of the severity (peeling, scaling, lichenification, erythema, papules) and extent (surface of affected skin areas) of skin disease at each application site is combined with patient's subjective scores (pain and pruritus). Higher scores indicate greater severity with a maximum of 100 points possible.
Measured: 42 days
Pharmacokinetics: plasma concentration
Concentration (ng/mL) of rhLEKTI in the plasma following topical application.
Measured: 42 days
Pharmacokinetics: skin concentration (Cmax skin)
Concentration of rhLEKTI in the skin (pmol/cm2), measured by tape stripping, following topical application.
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start16 Jun 2024
- Primary completion7 Jul 2026
- Study completion7 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Netherton SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Intrapatient, randomized controlled study: ATR12-351 will be applied to skin lesions on one side of the body, while the vehicle control will be applied to similar lesion on the other side of the body twice daily for 2 weeks. Each patient is randomized to receive ATR12-351 on either the left or right side.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azitra Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mary Spellman, MD, Study director, Azitra Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06137157
- Sponsor's protocol ID
- NTH201
- Status last verified
- Jul 2026
- First submitted
- 7 Nov 2023
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Vehicle-Controlled, First-in-Human Safety, Tolerability and Proof-of-Concept Study of Topical ATR12-351 in Adults With Netherton Syndrome
- ClinicalTrials.gov ID
- NCT06137157
- Acronym / sponsor ID
- NTH201
- Conditions
- Netherton Syndrome
- Keywords
- Ichthyosis, Netherton syndrome, Skin disease, ichthyosis linearis circumflexa
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Azitra Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Jun 2024 (actual)
- Primary completion
- 7 Jul 2026 (actual)
- Study completion
- 7 Jul 2026 (actual)
- First posted
- 18 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this clinical trial are to evaluate the safety and tolerability of topically applied ATR12-351, to understand what the body does to ATR12-351, and to observe treatment benefits of the drug in approximately 12 adult patients with Netherton Syndrome (NS). ATR12-351 will be applied to skin lesions on one side of the body, while the vehicle control will be applied to similar lesion on the other side of the body twice daily for 2 weeks.
Detailed description
Netherton syndrome (NS) is a rare but severe autosomal recessive disease that affects the skin, hair, and immune system. NS presents at birth with red skin covered by fine scales, a specific hair shaft abnormality ("bamboo hair"), atopic lesions, and elevated systemic immunoglobulin E (IgE) levels. Patients often develop allergies and asthma, and the unfortunate prognosis for infants with NS is poor, with 10% mortality in the first 6 months of life and recurrent infections. There are no FDA-approved treatment options for NS. NS is caused by mutations in in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI). Absence of LEKTI causes unregulated activity of proteases in the kallikrein subfamily, causing excessive desquamation of skin.
ATR12-351 is a topical ointment containing a lyophilized version of a live biotherapeutic product (LBP), Staphylococcus epidermidis (SE) strain designated SE351. This strain has been modified to be auxotrophic and to express recombinant human LEKTI protein (rhLEKTI). ATR12-351 is intended to address the underlying cause of NS by replacing deficient/dysfunctional LEKTI. The treatment consists of applying ATR12-351 to affected areas, where rhLEKTI produced by ATR12-351 will counter the dysregulated skin serine protease activity observed in NS patients.
This first-in-human study is a randomized, double-blind, vehicle-controlled clinical study to assess the safety, tolerability, and pharmacokinetics (PK) of topical ATR12-351 in approximately 12 adult Netherton syndrome patients who will serve as their own control. This study will include a 14-day treatment period to investigate the safety and tolerability of ATR12-351 applied to the skin and will be followed a total of 84 days for safety. The results of this first-in-human clinical study will establish safety and tolerability as well as initial efficacy of ATR12-351 application in Netherton syndrome patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Intrapatient, randomized controlled study: ATR12-351 will be applied to skin lesions on one side of the body, while the vehicle control will be applied to similar lesion on the other side of the body twice daily for 2 weeks. Each patient is randomized to receive ATR12-351 on either the left or right side.
| Arm | Type | Receives |
|---|---|---|
| Internal controlled arm | Experimental | Drug: ATR12-351ATR12-351 on left side of body, vehicle on right side of body in one group; vehicle on left side of body, ATR12-351 on right side of body. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults ≥18 years of age
- Confirmed mutation of the serine protease inhibitor of Kazal type 5 (SPINK5) gene
- Involvement of ≥20% of body surface area with skin changes consistent with Netherton syndrome
Key exclusion criteria (5 listed)
- Use of biologic therapies, antibiotics, antihistamines, corticosteroids, retinoids, disease-modifying antirheumatic drugs (DMARDs), immunosuppressive agents, phosphodiesterase-4 (PDE4) inhibitors, topical calcineurin inhibitors, or topical Janus kinase (JAK) inhibitors
- Open wounds or extensive areas of excoriation precluding identification of appropriate application sites in the Investigator's judgment
- Concurrent involvement in any other clinical study/expanded access program with an investigational drug or device or has participated in a clinical study within 30 days prior to the screening visit
- Residing with an immunocompromised person in the same dwelling from the baseline visit through 2 weeks after the treatment period
- History of ultraviolet phototherapy within the planned treatment area 4 weeks prior to baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATR12-351Also: ATR-12Topical ointment containing ATR12-351, a LEKTI-secreting strain of S. epidermidis | Drug | Internal controlled arm |
Primary outcome
Adverse events
Time frame: 84 days
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events
5 secondary outcomes
Investigator's Global Assessment (IGA)
Time frame: 42 days
Patient's Global Assessment (PGA)
Time frame: 42 days
NS-modified SCORAD
Time frame: 42 days
Pharmacokinetics: plasma concentration
Time frame: 42 days
Pharmacokinetics: skin concentration (Cmax skin)
Time frame: 42 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary Spellman, MD study director
Azitra Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ATR12-351 in people with Netherton Syndrome, run by Azitra Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.