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

Trial Summary

What is the purpose of this trial?

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.

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.

How is the drug ATR12-351 different from other treatments for Netherton Syndrome?

ATR12-351 is a topical treatment specifically developed for Netherton Syndrome, which is a rare condition with no standard effective therapies. Unlike other treatments that may have systemic absorption issues, ATR12-351 is designed to be applied directly to the skin, potentially minimizing systemic side effects. ^{1 2 3 4 5}

Research Team

Mary Spellman, MD

Principal Investigator

Azitra Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study. [2014]

3. Italy pubmed.ncbi.nlm.nih.gov

Netherton syndrome and its multifaceted defective protein LEKTI. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Successful treatment of Netherton syndrome with dupilumab: A case report and review of the literature. [2022]

5. Poland pubmed.ncbi.nlm.nih.gov

Ichthyosis linearis circumflexa in a child. Response to narrowband UVB therapy. [2020]