QRX003 Lotion for Netherton Syndrome

Not currently recruiting at 4 trial locations

Overseen By Oleg G Khatsenko

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Quoin Pharmaceuticals

Must not be taking: Systemic biologics, Topical prescriptions

Disqualifiers: Pregnancy, Active cancer, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new lotion, QRX003, to determine its effectiveness for people with Netherton Syndrome, a skin condition causing red, scaly patches. The study evaluates the lotion's safety and effectiveness at different strengths and frequencies. Participants will apply either a lotion with active ingredients (QRX003-2% Lotion or QRX003-4% Lotion) or a placebo (a lotion without active ingredients) on their skin for 12 weeks. Individuals with a confirmed diagnosis of Netherton Syndrome, especially those with visible skin symptoms on their arms or lower legs, may be suitable for this trial. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in treatment.

Do I need to stop my current medications to join the trial?

The trial requires you to stop certain medications. You must not use systemic prescription treatments for Netherton Syndrome within 4 weeks before starting the trial, systemic biologic therapy for NS, topical prescription treatments in the treatment area within 2 weeks before starting, or any topical moisturizers/emollients in the treatment area within 24 hours before starting.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications before participating. You must not use systemic prescription treatments for Netherton Syndrome within 4 weeks, topical prescription treatments in the treatment area within 2 weeks, or any topical moisturizers in the treatment area within 24 hours before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that QRX003 lotion appears safe. In one study, a child using QRX003 experienced improved skin with no adverse effects after two weeks. Another update reported no negative effects after using QRX003 over the entire body for six weeks. Additionally, another study found no safety issues and noted high patient satisfaction. These results are promising for those considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for Netherton Syndrome, which often involves topical steroids or emollients to manage symptoms, QRX003 Lotion offers a novel approach. Researchers are excited because QRX003 contains a unique ingredient that targets the underlying cause of the condition by stabilizing the skin barrier, potentially providing longer-lasting relief. The lotion comes in two concentrations, allowing flexibility in treatment intensity. Additionally, the option to apply it once or twice daily gives patients and doctors more choices in managing the condition effectively.

What evidence suggests that QRX003 Lotion might be an effective treatment for Netherton Syndrome?

Research shows that QRX003 lotion may help treat Netherton Syndrome (NS). In one study, a child using QRX003 experienced better skin health with no side effects after applying it twice a day for just two weeks. Another case demonstrated that after nine months of using QRX003, the patient's skin remained completely healed, suggesting the treatment's long-lasting benefits. These results indicate that regular use of QRX003 could lead to positive outcomes. In this trial, participants will receive different treatments: QRX003-2% applied once daily, QRX003-4% applied once or twice daily, or a vehicle lotion as a control. Additionally, the FDA has given QRX003 Orphan Drug Designation, highlighting its potential effectiveness and importance for treating NS. ^{1 2 3 5 6}

Who Is on the Research Team?

Tony Andrasfay

Principal Investigator

Therapeutics, Inc.

Are You a Good Fit for This Trial?

Adults with Netherton Syndrome (NS) who are in good health and have NS lesions on their arms or lower legs can join this trial. Women must not be pregnant, should use birth control, and have a negative pregnancy test. Participants shouldn't have used certain treatments for NS or any investigational drugs recently.

Inclusion Criteria

I have Netherton Syndrome and agree to genetic testing if I don't have SPINK5 mutation results.

I am not able to become pregnant, or I will use birth control during and 3 months after the study.

I am in good health with no conditions that would risk my safety in the study.

Exclusion Criteria

I have active cancer, not including non-melanoma skin cancer, outside the treatment area.

I have a skin condition in the treatment area that could affect the study's results.

I have used prescription skin treatment recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants apply QRX003 lotion or vehicle lotion for 12 weeks

12 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• QRX003-2% Lotion
• QRX003-4% Lotion
• Vehicle

Trial Overview The study is testing QRX003 lotion at two different strengths (2% and 4%) against a placebo lotion to see if they're safe, tolerable, and effective for treating Netherton Syndrome.

How Is the Trial Designed?

Group I: Vehicle Lotion Experimental Treatment 1 Intervention

Subjects will apply test article once daily in the morning (QAM) for 12 weeks

Group II: QRX003-4% QAM Experimental Treatment 1 Intervention

Subjects will apply test article once daily in the morning (QAM) for 12 weeks

Group III: QRX003-4% BID Experimental Treatment 1 Intervention

Subjects will apply test article twice daily BID for 12 weeks

Group IV: QRX003-2% QAM Experimental Treatment 1 Intervention

Subjects will apply test article once daily in the morning (QAM) for 12 weeks

Who Is Running the Clinical Trial?

Quoin Pharmaceuticals

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

Netherton's syndrome is a rare congenital condition in children that can present with various skin issues, such as ichthyosis linearis circumflexa and atopic symptoms, as seen in a case of a five-year-old boy with additional neurological complications.

Due to its nonspecific symptoms, Netherton's syndrome can be easily misdiagnosed as other skin disorders, highlighting the importance for pediatricians to include it in their differential diagnosis for generalized erythematous skin conditions in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of Netherton's syndrome with cerebral infarction. Calikoğlu, E., Anadolu, R., Sanli, H., et al.[2004]

An 11-year-old boy with Netherton syndrome developed Cushing syndrome after using 1% hydrocortisone ointment over his entire body for more than a year, highlighting the risks of systemic absorption in patients with compromised skin barrier function.

This case emphasizes the need for caution when using even low-potency topical steroids in Netherton syndrome, as long-term use in large quantities can lead to significant systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cushing syndrome from percutaneous absorption of 1% hydrocortisone ointment in Netherton syndrome. Halverstam, CP., Vachharajani, A., Mallory, SB.[2017]

There has been a significant increase in severe allergic reactions, including anaphylaxis, related to natural rubber exposure, particularly affecting patients with spina bifida and healthcare workers, with an estimated 2% to 10% of medical personnel being latex allergic.

Latex allergy can cause a range of reactions from contact dermatitis to systemic anaphylaxis, and while diagnosis often relies on clinical history, skin prick tests and serologic testing are available but have limitations in specificity and sensitivity. Prophylactic measures to reduce rubber exposure are recommended to prevent sensitization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allergic reaction to products made of natural rubber]. Antczak, M., Kuna, P., Cieślewicz, G.[2008]

Latex allergy is becoming more common due to the widespread use of latex products, with three main types of reactions: irritant contact dermatitis, allergic contact dermatitis, and Type I hypersensitivity, particularly affecting at-risk groups like children with spina bifida.

Diagnosis of latex allergy involves history, skin prick tests, and specific serum IgE tests, but avoidance of latex is the best prevention strategy, which is challenging due to the prevalence of latex products in everyday life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A discussion of natural rubber latex allergy with special reference to children: clinical considerations. Eustachio, N., Cristina, CM., Antonio, F., et al.[2019]

Two cases of Netherton syndrome, a rare genetic disorder affecting skin, showed significant improvement when treated with secukinumab, a medication that targets IL-17.

This suggests that IL-17 therapy could be a promising treatment option for managing the symptoms of Netherton syndrome, which currently lacks specific treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab use in the treatment of Netherton's syndrome. Gan, C., King, E., Orchard, D.[2022]

An 8-year-old boy with Netherton syndrome was initially misdiagnosed with severe atopic dermatitis, highlighting the importance of accurate and timely diagnosis for effective treatment.

Treatment with a low dose of oral acitretin (0.25 mg/kg) and a topical moisturizer led to significant improvement in the child's skin condition and pruritus within 2 months, with continued improvement observed at the 6-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An 8-Year-Old Child with Delayed Diagnosis of Netherton Syndrome. Leung, AKC., Barankin, B., Leong, KF.[2020]

The case study describes a patient with Netherton's syndrome, characterized by specific skin lesions and hair abnormalities, including ichthyosis linearis circumflexa and tricorrexis invaginata.

Treatment with etretinate was effective in managing the patient's skin and hair lesions, highlighting its potential as a therapeutic option for this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Netherton syndrome]. Moragón, M., Botella, R., Jiménez, A., et al.[2013]

Netherton syndrome is a rare genetic disorder characterized by specific symptoms including ichthyosis linearis circumflexa, atopic conditions, and unique hair shaft anomalies.

The diagnosis of Netherton syndrome in the presented patient was confirmed through the identification of 'matchstick' and 'golf tee' hair signs, alongside the classic hair shaft anomaly known as trichorrhexis invaginata.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and easy diagnosis of Netherton syndrome with dermoscopy. Meltem Akkurt, Z., Tuncel, T., Ayhan, E., et al.[2017]

A new human induced pluripotent stem cell (iPSC) line has been created from urine-derived cells of a patient with Netherton syndrome, which is caused by mutations in the SPINK5 gene.

This iPSC line can be used as a valuable research model to study the disease's pathogenesis and explore potential therapies for the severe skin barrier damage associated with Netherton syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of an induced pluripotent stem cell line (SAHGMUi001-A) from a patient with Netherton syndrome carrying SPINK5 mutation. Xu, M., Wang, L., Yin, J., et al.[2021]

Netherton syndrome (NS) is a severe genetic disorder linked to chromosome 5q32, identified through linkage analysis in 20 affected families, indicating a strong genetic basis for the condition.

This research marks a significant step towards identifying the NS gene, which could enhance our understanding of skin and immune system development, potentially leading to better treatments for affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping. Chavanas, S., Garner, C., Bodemer, C., et al.[2021]

A high incidence of positive patch test reactions to E45 cream was observed, with 118 out of 362 patients testing positive, indicating potential allergic reactions to its ingredients.

The main allergen identified was triethanolamine, while irritant reactions were linked to the formation of triethanolamine stearate in the cream, leading to a formulation change that will remove triethanolamine to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contact dermatitis from the old formula E45 cream. Batten, TL., Wakeel, RA., Douglas, WS., et al.[2019]

A study analyzing 16 brands of gloves marketed as 'accelerator-free' found that all gloves contained at least one rubber accelerator, contradicting their claims.

Specifically, dipentamethylenethiuram disulfide was detected in all gloves, and half of the samples contained multiple accelerators, highlighting a potential risk for patients with allergic contact dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are Rubber Gloves Marketed as Accelerator-Free Truly Free of Accelerators? Pillsbury, ME., Ronkainen, S., Goodier, M., et al.[2021]

A pediatric case of a Buschke-Lowenstein tumor in a patient with Netherton syndrome was successfully treated with surgery, demonstrating that surgical intervention can be safe in these patients despite concerns about wound healing complications.

The use of conventional dressings and topical negative-pressure therapy allowed for effective wound management and healing, suggesting that these methods can be beneficial in patients with Netherton syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations in surgical management of a Buschke-Lowenstein tumor in Netherton syndrome: A case report. Ashton, R., Moledina, J., Sivakumar, B., et al.[2018]

A retrospective study of 618 patients with suspected allergic contact dermatitis revealed that the most common allergens were nickel sulfate, thimerosal, and potassium bichromate.

The study found a statistically significant decrease in positive patch-test results for lanolin, neomycin, and anthraquinone over the years, suggesting these allergens may have a lower risk of sensitization and could potentially be excluded from standard testing in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patch test standard series recommended by the Brazilian Contact Dermatitis Study Group during the 2006-2011 period. Duarte, IA., Tanaka, GM., Suzuki, NM., et al.[2021]

Citations

1. investors.quoinpharma.com investors.quoinpharma.com/news-releases/news-release-details/quoin-pharmaceuticals-announces-further-clinical-evidence-qrx003

News Release These results strongly indicate that ongoing, chronic treatment with QRX003 is necessary for a continued positive clinical outcome in Netherton Syndrome ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06953466

Clinical Study of QRX003 Lotion in Subjects With ... The goal of this clinical trial (via an expanded access Treatment Protocol) is to learn if QRX003 (an investigational drug) applied topically to the skin

3. dermatologytimes.com dermatologytimes.com/view/quoin-reports-positive-qrx003-whole-body-pediatric-data-for-netherton-syndrome

Quoin Reports Positive QRX003 “Whole Body” Pediatric ... A pediatric patient using QRX003 saw an improved disease state with visually healed skin and no adverse effects after just 2 weeks of twice-daily application.

4. wate.com wate.com/business/press-releases/globenewswire/9562938/quoin-pharmaceuticals-announces-recruitment-of-three-additional-patients-in-investigator-pediatric-netherton-syndrome-study-and-provides-positive-9-month-whole-body-data-update-from

Quoin Pharmaceuticals Announces Recruitment of Three ... After 9 months of continued whole body application of QRX003, the subject's skin remains completely healed demonstrating the durability of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05521438

Safety, Tolerability and Efficacy of QRX003 Lotion in ... Safety, Tolerability and Efficacy of QRX003 Lotion in Subjects With Netherton Syndrome. ClinicalTrials.gov ID NCT05521438. Sponsor Quoin Pharmaceuticals.

6. muschealth.org muschealth.org/medical-services/dermatology/dermatology-research/get-involved/netherton-syndrome

Netherton Syndrome | MUSC Health | Charleston SC The purpose of this study is to assess the dose dependent safety, tolerability and potential efficacy of QRX003 lotion in subjects with Netherton Syndrome (NS).