Topical ATR12-351 for Netherton Syndrome

Recruiting at 1 trial location

Overseen By Travis Whitfill

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Azitra Inc.

Must not be taking: Biologics, Corticosteroids, Retinoids, others

Disqualifiers: Open wounds, Other clinical study, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new topical treatment called ATR12-351 for Netherton Syndrome, a rare skin condition. The main goal is to determine if ATR12-351 is safe and well-tolerated when applied to skin lesions. Researchers aim to understand how the body processes the treatment and whether it improves the condition. Ideal participants are adults with Netherton Syndrome affecting at least 20% of their skin. As a Phase 1 trial, this research focuses on understanding how ATR12-351 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, including biologic therapies, antibiotics, antihistamines, corticosteroids, retinoids, DMARDs, immunosuppressive agents, PDE4 inhibitors, topical calcineurin inhibitors, and topical JAK inhibitors, to participate in this trial.

Is there any evidence suggesting that ATR12-351 is likely to be safe for humans?

Research has shown that ATR12-351 was safe and well-tolerated in earlier studies. Participants mostly experienced mild to moderate symptoms at the application site, and these symptoms were temporary. This suggests the treatment is unlikely to cause serious side effects and should be manageable for most people. However, as with any new treatment, individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Netherton Syndrome?

Researchers are excited about ATR12-351 for treating Netherton Syndrome because it offers a novel approach compared to standard therapies like topical steroids and emollients. Unlike these treatments, ATR12-351 is a topical application designed to target the underlying genetic causes of the condition. It specifically focuses on correcting the skin barrier dysfunction by potentially enhancing the skin's natural ability to retain moisture and protect against irritants. This targeted action could lead to more effective and longer-lasting relief for patients.

What evidence suggests that ATR12-351 might be an effective treatment for Netherton Syndrome?

Research has shown that ATR12-351 might help treat Netherton Syndrome, based on encouraging early studies. In these studies, applying ATR12-351 to the skin significantly reduced a protein called IL-36γ by 93%. IL-36γ is associated with skin inflammation, a problem in Netherton Syndrome. Additionally, ATR12-351 proved generally safe in initial trials, causing only mild to moderate, short-lived symptoms at the application site. These findings suggest that ATR12-351 could help manage symptoms for people with Netherton Syndrome. ^{1 2 5 6 7}

Who Is on the Research Team?

Mary Spellman, MD

Principal Investigator

Azitra Inc.

Are You a Good Fit for This Trial?

Adults over 18 with Netherton Syndrome, affecting at least 20% of their body and confirmed SPINK5 gene mutation. Participants should not be using certain medications like biologics, antibiotics, or steroids, nor have had recent phototherapy or other clinical trials within the last month.

Inclusion Criteria

Over 20% of my skin is affected by Netherton syndrome.

My condition involves a SPINK5 gene mutation.

Exclusion Criteria

I am not currently in any clinical trials or have been in one within the last 30 days.

I haven't had UV light treatment on the area to be treated in the last 4 weeks.

I am not currently using any immune system affecting drugs like steroids or biologics.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATR12-351 applied to skin lesions on one side of the body, while the vehicle control is applied to similar lesions on the other side twice daily for 2 weeks

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATR12-351

Trial Overview The trial tests ATR12-351's safety and effects when applied to skin lesions in adults with Netherton Syndrome. One side of the body receives ATR12-351 while the other gets a control treatment for comparison, twice daily for two weeks.

How Is the Trial Designed?

Group I: Internal controlled arm Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Azitra Inc.

Lead Sponsor

Trials

4

Recruited

130+

Published Research Related to This Trial

A case of Netherton syndrome (NS), a rare genetic disorder caused by mutations in the SPINK5 gene, was confirmed through whole exome sequencing, identifying two new mutations from the patient's parents.

The patient showed significant clinical improvement after treatment with dupilumab, a medication typically used for other conditions, with no reported adverse effects, suggesting potential for dupilumab as a safe therapeutic option for NS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of Netherton syndrome with dupilumab: A case report and review of the literature. Wang, J., Yu, L., Zhang, S., et al.[2022]

Topical treatments with tacrolimus and pimecrolimus were effective in controlling skin symptoms in four siblings with Netherton's syndrome, demonstrating a promising therapeutic option for this rare condition.

This case report highlights the safety of using these topical calcineurin inhibitors, as the siblings experienced good control of their skin disease without any toxic effects, addressing concerns about systemic absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. Bin Saif, G., Al-Khenaizan, S.[2015]

A 12-year-old patient with ichthyosis linearis circumflexa showed significant improvement after 30 sessions of narrowband UVB phototherapy, suggesting its potential efficacy.

Narrowband UVB phototherapy may be a promising short-term treatment option for patients with ichthyosis linearis circumflexa and Netherton syndrome, which often have compromised skin barrier function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ichthyosis linearis circumflexa in a child. Response to narrowband UVB therapy. Singer, R., Çopur, M., Yüksel, EN., et al.[2020]

Netherton syndrome (NS) is a rare genetic disorder caused by mutations in the SPINK5 gene, leading to severe skin and hair abnormalities, and often poor prognosis in infancy due to complications.

While diagnostic tools have improved the ability to identify NS, there is currently no specific treatment available, highlighting the ongoing need for innovative therapies to manage this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Netherton syndrome and its multifaceted defective protein LEKTI. D'Alessio, M., Fortugno, P., Zambruno, G., et al.[2017]

In a study involving 3 children with Netherton syndrome, the topical application of pimecrolimus, 1% cream over 18 months was well tolerated, with no significant abnormalities in blood tests and low systemic absorption levels (0.625 to 7.08 ng/mL).

The treatment led to significant improvements in skin condition and symptoms, with rapid responses observed within the first month, indicating its potential efficacy for managing Netherton syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study. Yan, AC., Honig, PJ., Ming, ME., et al.[2014]

Citations

1. ir.azitrainc.com ir.azitrainc.com/news-releases/news-release-details/azitra-reports-promising-safety-data-phase-1b-trial-netherton

Azitra Reports Promising Safety Data from Phase 1b Trial in ... Drug candidate ATR12-351 has been generally safe and well-tolerated with occasional, transient, mild to moderate symptoms at application ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06137157

NCT06137157 | Evaluation of Topical ATR12-351 in Adults ... 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 ...

3. prnewswire.com prnewswire.com/news-releases/azitra-reports-promising-safety-data-from-phase-1b-trial-in-netherton-syndrome-302483136.html

Azitra Reports Promising Safety Data from Phase 1b Trial ... Drug candidate ATR12-351 has been generally safe and well-tolerated with occasional, transient, mild to moderate symptoms at application ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/azitra-trial-netherton-syndrome/

Azitra screens subject in trial of ATR-12 for Netherton ... The design of the trial is based on strong preclinical data, which includes the topical use of ATR-12 offering a 93% reduction in IL-36γ levels ...

5. synapse.patsnap.com synapse.patsnap.com/article/azitra-screens-first-patient-for-phase-1b-atr-12-trial-for-netherton-syndrome

Azitra Screens First Patient for Phase 1b ATR-12 Trial ... Azitra has secured clinical sites and identified patients with Netherton syndrome for this 12-patient Phase 1b trial, which will assess safety, ...

6. firstwordpharma.com firstwordpharma.com/story/5988268

Azitra, Inc. Announces Q2 2025 Results and Provides ... "For ATR-12, our lead program targeting the rare, chronic and devastating Netherton syndrome, we announced promising safety data in the first ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06137157?term=AREA%5BConditionSearch%5D(%22Netherton%20Syndrome%22)&rank=1

Evaluation of Topical ATR12-351 in Adults With Netherton ... 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, ...