Tralokinumab + Topical Corticosteroids for Eczema

(TRAPEDS 2 Trial)

Recruiting at 52 trial locations

Overseen By Clinical Disclosure

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: LEO Pharma

Must not be taking: Immunosuppressants, Corticosteroids, Calcineurin inhibitors, others

Disqualifiers: Active infections, Hepatitis B or C, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 196 weeks

195 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this trial is to test whether treatment with tralokinumab (administered subcutaneous injections \[SC\]) in combination with topical corticosteroids (TCS) is safe and effective to treat moderate-to-severe atopic dermatitis (AD) in children and infants. This will be judged by a range of assessments that rate the severity and extent of atopic dermatitis and its symptoms, as well as general health status and quality of life. The trial will last for up to 4 years. There will be visits every 2 weeks for the first year and every 6 weeks thereafter. Some of the visits will be conducted by phone. The study involves two different age groups: children aged 2 to under 12 years and infants aged 6 months to under 2 years. This trial compares tralokinumab +TCS to placebo + TCS for children with moderate-to-severe AD and evaluates tralokinumab + TCS for infants with moderate-to-severe AD. Infants will not receive placebo. All subjects will go through a screening process, which is the first part of the trial and will last up to 4 weeks. During this period, it will be checked if the child or infant meets the criteria to participate in the trial. The children will be randomly assigned to receive tralokinumab + TCS or placebo + TCS for the initial 16 weeks, with the treatment being double-blinded. During the first 16 weeks, children will have a 2 out of 3 chance of getting tralokinumab and a 1 out of 3 chance of getting placebo. Thereafter, all subjects will receive tralokinumab + TCS. The infants will receive tralokinumab + TCS as open-label treatment for the entire treatment period, meaning that the participants will know they are receiving tralokinumab. After stopping treatment, all participants will enter a 4-week safety follow-up period.

Will I have to stop taking my current medications?

Yes, you will need to stop certain medications before joining the trial. Specifically, you must stop using topical corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors, and Janus kinase inhibitors at least 1 week before starting, and systemic immunosuppressive drugs and corticosteroids 4 weeks before starting.

What data supports the effectiveness of the drug Tralokinumab + Topical Corticosteroids for eczema?

The research shows that topical corticosteroids are effective in treating skin conditions like psoriasis and eczema, as they help reduce inflammation and heal the skin. While the studies focus on psoriasis, the effectiveness of corticosteroids in reducing skin inflammation suggests they may also be beneficial when used with Tralokinumab for eczema. ^{1 2 3 4 5}

Is Tralokinumab + Topical Corticosteroids safe for treating eczema?

Topical corticosteroids are generally safe for treating eczema, but a small number of people may develop a contact allergy to them. This is uncommon, but if eczema worsens or doesn't improve, an allergy test might be needed. ^{6 7 8 9 10}

How does the drug Tralokinumab differ from other eczema treatments?

Tralokinumab is unique because it targets and blocks a specific protein called interleukin-13 (IL-13), which plays a key role in the inflammation associated with eczema, unlike traditional treatments that often use topical corticosteroids. This approach may reduce the risk of side effects commonly associated with long-term steroid use. ^{3 7 11 12 13}

Research Team

Medical Expert

Principal Investigator

LEO Pharma

Eligibility Criteria

This trial is for children and infants aged 6 months to under 12 years with moderate-to-severe atopic dermatitis (eczema) who haven't improved with mid-strength topical corticosteroids. They must weigh at least 9 kg, have had AD for a minimum of 3-12 months depending on age, and show significant itchiness or scratching.

Inclusion Criteria

My skin condition didn't improve after using a prescribed cream in the last 6 months.

My body weight is at least 9 kg.

I am between 6 months and 12 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Children receive tralokinumab + TCS or placebo + TCS for 16 weeks, then all receive tralokinumab + TCS; infants receive open-label tralokinumab + TCS

196 weeks

Visits every 2 weeks for the first year, then every 6 weeks; some visits by phone

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tralokinumab

Trial Overview The trial tests if tralokinumab injections plus topical corticosteroids are more effective than placebo plus TCS in treating eczema. Children will be randomly assigned to treatments for the first 16 weeks; then all get tralokinumab + TCS. Infants receive only the actual drug from the start.

Participant Groups

Group I: Tralokinumab + TCS for subjects aged 6 months to <2 years Experimental Treatment 1 Intervention

Dose and dosing frequency for each subject will depend on the subject's body weight.

Group II: Tralokinumab + TCS for subjects aged 2 to <12 years Experimental Treatment 1 Intervention

Dose and dosing frequency for each subject will depend on the subject's body weight.

Group III: Placebo + TCS for subjects aged 2 to <12 years Experimental Treatment 1 Intervention

Dose and dosing frequency for each subject will depend on the subject's body weight.

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

Approved in United States as Adbry for:

• Moderate-to-severe atopic dermatitis

Approved in European Union as Adtralza for:

• Moderate-to-severe atopic dermatitis

Approved in Canada as Adtralza for:

• Moderate-to-severe atopic dermatitis

Who Is Running the Clinical Trial?

LEO Pharma

Lead Sponsor

Trials

275

Recruited

189,000+

Christophe Bourdon

LEO Pharma

Chief Executive Officer since 2022

Engineering degree from Université de Technologie de Compiègne

Dr. Siri Torhaug

LEO Pharma

Chief Medical Officer since 2022

MD, PhD

Findings from Research

A systematic review of 11 studies found that nonadherence to topical corticosteroids in psoriasis patients varied widely, with rates ranging from 8% to 88.3%, highlighting a significant challenge in treatment effectiveness.

The study identified 34 factors contributing to nonadherence and noted that a disease management program improved adherence, suggesting that targeted interventions could enhance treatment outcomes for psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical adherence to topical corticosteroid preparations prescribed for psoriasis: A systematic review. Svendsen, MT., Andersen, F., Hansen, J., et al.[2018]

In a pilot study involving Italian adults with eczema, the new non-steroid anti-inflammatory cream showed effectiveness in reducing eczema severity, with recovery rates of 58.3% in the non-steroid group compared to 91.7% in the Hydrocortisone group when following the treatment protocol closely.

While Hydrocortisone Butyrate 0.1% Cream was more effective overall, the non-steroid cream demonstrated significant clinical improvement at each assessment point, suggesting it could be a viable long-term treatment option for eczema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non steroid treatment for eczema: results from a controlled and randomized study. De Waure, C., Cadeddu, C., Venditti, A., et al.[2015]

In a study involving eight patients with chronic psoriatic plaques, clobetasol, betamethasone, and triamcinolone were effective in healing lesions within one week when occluded with a hydrocolloid dressing, while hydrocortisone showed better results than the untreated control area.

In a larger group of 44 patients with various skin conditions, betamethasone applied weekly under the same dressing led to healing of lesions, demonstrating the efficacy of this treatment method for multiple dermatological issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of psoriasis and other dermatoses with a single application of a corticosteroid left under a hydrocolloid occlusive dressing for one week. Juhlin, L.[2004]

In a study involving outpatients with chronic plaque-type psoriasis, the combination of a hydrocolloid dermatologic patch (Actiderm) and topical beta-methasone valerate cream led to significant lesion resolution after three weeks of treatment.

In contrast, using either the patch or the steroid cream alone resulted in only mild and insignificant improvements, highlighting the patch's effectiveness as an important addition to psoriasis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic response to a dermatologic patch and betamethasone valerate 0.1 percent cream in the management of chronic plaques in psoriasis. Wilkinson, RD., Ohayon, M.[2013]

Corticophobia, or fear of using topical corticosteroids, is prevalent among both parents of children with atopic dermatitis and health care professionals, with parents and public health care nurses scoring equally high at 44%.

The study found that general practitioners and pediatricians had lower corticophobia scores (39% and 31%, respectively), indicating that the type of profession and personal experience with atopic dermatitis significantly influence beliefs about corticosteroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroid phobia (corticophobia) in parents of young children with atopic dermatitis and their health care providers. Bos, B., Antonescu, I., Osinga, H., et al.[2019]

Topical corticosteroids (TCS) used for atopic eczema showed no significant increased risk of skin thinning in short-term studies, indicating they are generally safe for use in both adults and children.

While TCS may have a higher relative risk of skin thinning compared to topical calcineurin inhibitors, the overall long-term safety data is limited, suggesting that intermittent use of TCS is safe but requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of topical corticosteroids in atopic eczema: an umbrella review. Axon, E., Chalmers, JR., Santer, M., et al.[2023]

In a study of 2,742 eczema patients, only 2.4% had a positive patch test reaction to corticosteroids, indicating that contact dermatitis from these medications is relatively uncommon.

Budesonide was the most frequently identified allergen among corticosteroids, suggesting that while corticosteroid contact allergy is rare, it should be considered in patients with persistent eczema who do not respond to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Contact allergy to local steroids. Contact allergy to corticosteroids among consecutively tested patients with eczema]. Vestergaard, L., Andersen, KE.[2006]

In a randomized controlled trial involving 40 children with severe atopic eczema, both methotrexate and ciclosporin showed similar efficacy in reducing eczema severity after 12 weeks, with no significant difference in the SCORAD index scores (P = 0.93).

Both treatments were associated with minor adverse effects, indicating that they are relatively safe and well tolerated for managing severe atopic eczema in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: a critical appraisal. Tsakok, T., Flohr, C.[2022]

In two studies involving 631 adults with moderate to severe atopic dermatitis, tacrolimus ointment (0.03% or 0.1%) was found to be effective, significantly outperforming the vehicle in all measured efficacy parameters over 12 weeks.

While some patients experienced mild adverse events like skin burning and pruritus, these were generally brief and resolved quickly; importantly, tacrolimus ointment was deemed safe, with no significant laboratory changes and low systemic absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. Soter, NA., Fleischer, AB., Webster, GF., et al.[2022]

Topical tacrolimus ointment has been shown to be effective for treating atopic dermatitis, with its safety and efficacy established through various clinical trials lasting up to 12 weeks and comparative studies with topical steroids.

Long-term safety studies extending up to 4 years provide additional reassurance about the use of tacrolimus ointment, addressing clinicians' concerns regarding its prolonged use in patients with atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of tacrolimus ointment: a clinical review. Beck, LA.[2013]

A double-blind study found that a new treatment combining 1% hydrocortisone with 10% urea was as effective as hydrocortisone 17-valerate in improving symptoms of atopic dermatitis in patients.

Importantly, the combination treatment with hydrocortisone and urea did not cause any side effects, making it a safer alternative to traditional corticosteroid treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Urea in combination with corticosteroids in treating eczema]. Drosner, M.[2015]

Anakinra, an interleukin-1 receptor antagonist, shows promising efficacy for various dermatologic conditions, particularly hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome, based on a review of available studies and case reports.

With a relatively benign adverse effect profile, anakinra may be a valuable treatment option for patients with difficult-to-treat dermatologic diseases that do not respond to standard therapies, although more high-quality research is needed to better define its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label studies on anakinra in dermatology: a review. Tegtmeyer, K., Atassi, G., Zhao, J., et al.[2022]

Tacrolimus 0.1% ointment is more effective than low-potency corticosteroids and pimecrolimus 1% in treating moderate to severe atopic dermatitis, based on a systematic review of 20 studies involving 5885 participants.

Both formulations of tacrolimus (0.1% and 0.03%) appear to be safe, with no evidence of increased risk for malignancies or skin atrophy, and serious adverse events were rare and generally unrelated to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical tacrolimus for atopic dermatitis. Cury Martins, J., Martins, C., Aoki, V., et al.[2023]

References

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

Medical adherence to topical corticosteroid preparations prescribed for psoriasis: A systematic review. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

Non steroid treatment for eczema: results from a controlled and randomized study. [2015]

3. Sweden pubmed.ncbi.nlm.nih.gov

Treatment of psoriasis and other dermatoses with a single application of a corticosteroid left under a hydrocolloid occlusive dressing for one week. [2004]

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

Therapeutic response to a dermatologic patch and betamethasone valerate 0.1 percent cream in the management of chronic plaques in psoriasis. [2013]

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

Corticosteroid phobia (corticophobia) in parents of young children with atopic dermatitis and their health care providers. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety of topical corticosteroids in atopic eczema: an umbrella review. [2023]

7. Denmark pubmed.ncbi.nlm.nih.gov

[Contact allergy to local steroids. Contact allergy to corticosteroids among consecutively tested patients with eczema]. [2006]

8. England pubmed.ncbi.nlm.nih.gov

Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: a critical appraisal. [2022]

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

Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. [2022]

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

The efficacy and safety of tacrolimus ointment: a clinical review. [2013]

11. Germany pubmed.ncbi.nlm.nih.gov

[Urea in combination with corticosteroids in treating eczema]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Off-Label studies on anakinra in dermatology: a review. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Topical tacrolimus for atopic dermatitis. [2023]