Ustekinumab for Ichthyosis

Overseen By NU Dermatology CTU

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: Systemic retinoids, Anti-inflammatories, Topical steroids

Disqualifiers: Ichthyosis vulgaris, X-linked ichthyosis, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug ustekinumab can reduce inflammation and improve symptoms in people with ichthyosis, a group of rare genetic skin disorders that cause thick, scaly skin and discomfort. The researchers aim to determine if ustekinumab, which targets specific inflammation pathways, can enhance the quality of life for those affected. Suitable candidates for this trial are individuals aged 6 and up with a confirmed diagnosis of ichthyosis who experience significant skin redness due to their condition. As an Early Phase 1 trial, this research focuses on understanding how ustekinumab works in people, offering participants a chance to be among the first to potentially benefit from this new treatment approach.

Will I have to stop taking my current medications?

The trial requires that you stop using any systemic retinoid or systemic anti-inflammatory agent at least 4 weeks before starting, and you must not use topical steroids in the week before starting or retinoid or keratolytic agents in the 24 hours before starting.

Is there any evidence suggesting that ustekinumab is likely to be safe for humans?

Research has shown that ustekinumab, a drug affecting certain pathways in the body, has been used in people with conditions similar to ichthyosis. Some studies have examined its safety. For instance, one study found that 5% to 8.6% of patients experienced serious side effects during treatment, indicating that most did not have severe problems. This suggests that ustekinumab is generally well-tolerated by many.

Ustekinumab is already approved for treating other conditions, such as psoriasis, which provides additional confidence about its safety. However, since this trial is in its early stages, much remains to be learned about its safety for ichthyosis specifically. Current data indicate that while there are some risks, the treatment might be safe for most people. ^{1 2 3 4 5}

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

Ustekinumab is unique because it targets specific proteins in the immune system, potentially reducing the inflammation that contributes to ichthyosis. Unlike standard treatments like topical emollients and retinoids that primarily focus on symptom relief, ustekinumab offers a more targeted approach by inhibiting interleukin-12 and interleukin-23. Researchers are excited about this treatment because it could address the underlying immune response in ichthyosis, providing a new way to manage the condition beyond surface-level symptom control.

What evidence suggests that ustekinumab might be an effective treatment for ichthyosis?

Research has shown that ustekinumab, a medication effective for psoriasis, might also benefit those with ichthyosis. Ichthyosis is a genetic skin condition characterized by thick, scaly skin. Studies have found that ustekinumab can improve skin conditions similar to ichthyosis. Some patients reported smoother skin and reduced itching after starting ustekinumab. Although specific data for ichthyosis is limited, the drug targets the same inflammation process present in both psoriasis and ichthyosis. This trial will evaluate ustekinumab's potential to reduce inflammation and improve skin symptoms in people with ichthyosis. ^{2 5 6 7 8}

Who Is on the Research Team?

Amy Paller, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for children (6+) and adults with ichthyosis who have not used certain medications targeting IL-12/IL-23, steroids, or retinoids within specific time frames before the study. Participants must test negative for TB, Hepatitis B/C, HIV, be immunocompetent and agree to contraception requirements.

Inclusion Criteria

I am a man who can father children and will use contraception during and 16 weeks after the study.

You need to have a negative test for tuberculosis, hepatitis B, hepatitis C, and HIV before starting the study.

I am either postmenopausal or, if of childbearing age, I am following specific contraceptive guidelines.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant.

I am under 6 years old.

I can give my own consent or have someone legally allowed to do so if I'm under 18.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ustekinumab to assess clinical response and safety for ichthyotic disorders

7 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue to receive ustekinumab to evaluate long-term efficacy and safety

What Are the Treatments Tested in This Trial?

Interventions

• Ustekinumab

Trial Overview The trial tests Ustekinumab's effectiveness in treating ichthyoses by reducing skin inflammation. It's an open-label study where all participants know they're receiving the drug. The goal is to see if this treatment can improve their quality of life.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Ustekinumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Stelara for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Approved in United States as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Canada as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Japan as Stelara for:

• Plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

This case report highlights a rare instance of severe Staphylococcus aureus infection in a 64-year-old woman who had recently received ustekinumab for psoriatic arthritis, suggesting that while ustekinumab is generally safe, clinicians should remain vigilant for potential severe infections in patients on biological therapies.

The report emphasizes the importance of ongoing monitoring for rare but serious infections in patients treated with biologicals like ustekinumab, as symptoms may be nonspecific and fever may not always be present, necessitating thorough investigation when inflammatory markers are elevated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab. Joost, I., Steinfurt, J., Meyer, PT., et al.[2018]

Ustekinumab is an effective treatment for adults with active psoriatic arthritis, showing significant improvement compared to placebo in phase 3 trials, with benefits maintained up to 100 weeks.

The drug has a favorable safety profile, with rare occurrences of serious infections or major cardiovascular events, making it a valuable option for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. McKeage, K.[2021]

A 71-year-old male patient developed eosinophilic pneumonia after being treated with ustekinumab for severe psoriasis, highlighting a potential adverse effect of this medication.

After discontinuing ustekinumab and starting corticosteroid treatment, the patient's symptoms resolved, indicating that eosinophilic pneumonia can improve with treatment withdrawal and corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ustekinumab-induced eosinophilic pneumonia during the course of ustekinumab therapy for plaque psoriasis]. Amy de la Bretèque, M., Appere-De Vecchi, C., Zeboulon, C., et al.[2015]

Ustekinumab (STELARA) is a safe and effective treatment for skin conditions related to inflammatory bowel diseases (IBD), including metastatic Crohn's disease and pyoderma gangrenosum, based on a review of 22 articles.

It also effectively addresses paradoxical skin reactions caused by TNF-α inhibitors, such as psoriasis, particularly when these reactions do not improve with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. Wu, J., Smogorzewski, J.[2021]

Citations

1. ejhp.bmj.com ejhp.bmj.com/content/30/Suppl_1/A227.3

6ER-018 Off-label use of ustekinumab in refractory ... Conclusion and Relevance Ustekinumab is suggested to be an alternative therapy in some severe EI subtypes refractory to topical and systemic treatments. In ...

2. academic.oup.com academic.oup.com/bjd/advance-article/7848640

Biologics in congenital ichthyosis: are they effective? At the time of analysis, treatment was ongoing in 43 of 98 (44%) patients (Table 2). The remaining 55 (56%) patients discontinued the biologic, ...

3. ejhp.bmj.com ejhp.bmj.com/content/30/Suppl_1/A37.2

4CPS-042 Off-label use of ustekinumab in nonbullous ... At the 3rd month of treatment, the patient observed a mild improvement while presenting diffused erythema with scaling and rough skin in the folds, with an ...

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/stelara/medical-content/stelara-treatment-of-ichthyosis

STELARA - Treatment of Ichthyosis Systemic acitretin resulted in significant improvement in PPK and ichthyosis. STELARA therapy was initiated, resulting in itch improvement after 4 weeks.

5. withpower.com withpower.com/trial/early-phase-1-ichthyosis-3-2021-bd670

Ustekinumab for Ichthyosis · Info for Participants Ustekinumab has been shown to be effective in treating moderate to severe plaque psoriasis and psoriatic arthritis, as well as other skin conditions like ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10188215/

Assessing the Use of Ustekinumab in a Pediatric Patient ... There was an initial mild improvement in his erythema within one month of treatment, but by his one-year follow-up, ustekinumab had failed to ...

7. jaad.org jaad.org/article/S0190-9622(15)00939-1/pdf

Safety and efficacy of ustekinumab in adolescent patients ... Results: 123 residents responded (41.8% response rate), representing approxi- mately 29.1% of the total number of graduating residents. 69 (56.1%) residents.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK409638/

DETAILED OUTCOME DATA - Ustekinumab (Stelara) Injection Through week 60, 5.0% and 8.6% of patients experienced at least one treatment-emergent serious adverse event in the combined 45 mg and 90 mg group, respectively ...