Ruxolitinib Cream for Eczema

(TRuE-AD4 Trial)

No longer recruiting at 132 trial locations

Overseen By Incyte Corporation Call Center (US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: Biologics, Systemic corticosteroids

Disqualifiers: Immunocompromised, Hepatitis B/C, HIV, others

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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a cream called ruxolitinib to determine its effectiveness for people with moderate eczema who haven't found success with common treatments. Participants will apply either the ruxolitinib cream or a placebo cream to affected skin areas twice daily over varying periods. It suits individuals who have had eczema for at least two years and haven't responded well to other creams. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to access a potentially effective treatment early.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications used to treat eczema, except for those allowed in the study. There are specific timeframes for stopping certain medications, such as 4 weeks for systemic corticosteroids and 1 week for other topical treatments.

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

Research has shown that ruxolitinib cream is generally safe and effective for patients. In earlier studies, most participants experienced significant improvements in their eczema symptoms. These studies also confirmed the cream's safety. One study found that after eight weeks of use, participants noticed clear improvements in their skin. Another study demonstrated that these benefits lasted for up to 52 weeks. Most participants did not experience serious side effects, making it a promising treatment for those with moderate eczema. ^{1 2 3 4 5}

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

Ruxolitinib cream is unique because it specifically targets the JAK-STAT pathway, which plays a key role in the inflammatory process of eczema. Unlike traditional treatments like corticosteroids and calcineurin inhibitors that broadly suppress the immune response, ruxolitinib offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about this treatment because it may provide faster relief and improved outcomes for eczema sufferers, especially those who have not found success with current therapies.

What evidence suggests that ruxolitinib cream might be an effective treatment for eczema?

Research has shown that ruxolitinib cream effectively treats eczema, also known as atopic dermatitis. In earlier studies, most participants using this cream experienced their skin clearing up or nearly clearing up, with noticeable improvement. By the second week, many reported feeling better and having fewer symptoms, with these benefits lasting up to a year. Another study found that ruxolitinib cream significantly reduced the need for other eczema treatments, such as steroid creams. Overall, ruxolitinib cream is a safe and effective option for individuals with mild to moderate eczema who haven't had success with other treatments. Participants in this trial will receive either ruxolitinib 1.5% cream or a vehicle cream as a comparator, applied topically to the affected areas. ^{1 2 3 5 6}

Who Is on the Research Team?

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

Adults over 18 with moderate atopic dermatitis (AD) covering 10-20% of their body, not including the scalp. They must have had AD for at least two years and not responded well to or can't use topical steroids and calcineurin inhibitors. Participants need an IGA score of 3, EASI score above 7, significant itchiness, and a DLQI score over 10.

Inclusion Criteria

I agree to stop all current Alzheimer's treatments except those allowed in the study.

EASI score > 7 at screening and Day 1

DLQI score > 10 at screening and Day 1

Exclusion Criteria

I haven't taken antibiotics or antivirals in the last 2 weeks.

Any other concomitant skin disorder (eg, generalized erythroderma, such as Netherton syndrome), pigmentation, or extensive scarring that, in the opinion of the investigator, may interfere with the evaluation of AD lesions or compromise participant safety

Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib 1.5% cream or vehicle cream applied topically twice daily from Day 1 to Week 8 during the Vehicle Control (VC) Period

8 weeks

Regular visits for assessment

Extension

Participants continue applying ruxolitinib 1.5% cream or vehicle cream from Week 8 to 24 during the Vehicle Control Extension (VCE) Period

16 weeks

Regular visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib Cream

Trial Overview The trial is testing Ruxolitinib Cream against a placebo cream (Vehicle Cream) in adults with moderate AD who haven't seen improvement from standard treatments like topical steroids or are unable to use them due to intolerance or contraindications.

How Is the Trial Designed?

Group I: VC Period: Ruxolitinib 1.5% Cream BID Experimental Treatment 1 Intervention

Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film twice daily (BID) from Day 1 to Week 8 during the Vehicle Control (VC) Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Group II: VC Extension Period: Ruxolitinib 1.5% cream open-label escape arm Experimental Treatment 1 Intervention

Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film twice daily (BID) during the VCE Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Group III: VC Extension Period/Escape Arm: Ruxolitinib 1.5% Cream BID Experimental Treatment 1 Intervention

Participants who applied ruxolitinib 1.5% cream during VC Period, continued applying ruxolitinib 1.5% cream topically to the affected areas as a thin film BID from Week 8 to 24 during the Vehicle Control Extension (VCE) Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Group IV: VC Period: Vehicle Cream BID Placebo Group 1 Intervention

Participants received vehicle cream, applied topically to the affected areas as a thin film twice daily (BID) from Day 1 to Week 8 during the VC Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Group V: VC Extension Period/Escape Arm: Vehicle Cream BID Placebo Group 1 Intervention

Participants who applied vehicle cream during the VC Period, continued applying vehicle cream as a thin film twice daily (BID) from Weeks 8 to 24 during the VCE Period. Participants applied cream BID to areas identified at Baseline even if the areas improved. Participants will be eligible to enter the ruxolitinib 1.5% cream open-label escape arm as defined in the protocol.

Ruxolitinib Cream is already approved in United States, European Union for the following indications:

Approved in United States as Opzelura for:

• Atopic Dermatitis
• Vitiligo

Approved in European Union as Jakavi for:

• Myelofibrosis
• Polycythaemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

JAK inhibitors, including upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib, have been found to have a generally favorable long-term safety profile for treating various dermatological conditions, based on a review of literature from 2000 to 2023.

The review identified 37 dermatological disorders where JAK inhibitors are supported for use, indicating their potential as effective treatment options for a wide range of skin disorders, including off-label applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. Corbella-Bagot, L., Riquelme-McLoughlin, C., Morgado-Carrasco, D.[2023]

Ruxolitinib cream, a topical treatment for atopic dermatitis, was found to be generally well tolerated in a study of 41 patients aged 12 to 65, with only 31.7% experiencing treatment-emergent adverse events, and only 9.8% reporting treatment-related adverse events.

The cream demonstrated high efficacy, with 94.6% of patients achieving at least a 75% improvement in their eczema severity after 56 days of treatment, while the mean plasma concentration of the drug remained well below levels that could cause harmful effects on bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. Bissonnette, R., Call, RS., Raoof, T., et al.[2022]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

In two phase 3 trials involving 1249 patients with atopic dermatitis, ruxolitinib cream showed rapid and significant reductions in itch, with over 16% of patients experiencing a 2-point reduction within 12 hours compared to only 6.9% with the vehicle cream.

By Day 2, a greater percentage of patients using ruxolitinib cream achieved a 4-point reduction in itch severity, with sustained improvements observed over the 8-week treatment period, indicating both efficacy and a quick onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. Blauvelt, A., Kircik, L., Papp, KA., et al.[2023]

Ruxolitinib 1.5% cream is the first FDA-approved topical JAK inhibitor for atopic dermatitis (AD), showing high efficacy in treating this chronic skin condition.

The cream has a favorable safety profile, making it a promising new option for patients suffering from the pruritic and inflammatory symptoms of AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Atopic Dermatitis: Clinical Utility of Ruxolitinib. Owji, S., Caldas, SA., Ungar, B.[2022]

In a pilot study involving 10 patients with mild atopic dermatitis, a topical emulgel containing ruxolitinib significantly improved skin condition, reducing symptoms like itching and burning after four weeks of treatment.

The treatment also enhanced skin hydration and density, indicating good short-term efficacy and tolerability for patients with mild atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of tolerability and efficacy of a topical emulgel containing nanoliposomal ruxolitinib phosphate in the treatment of mild atopic dermatitis: a before-after single group pilot study. Naeimifar, A., Ahmad Nasrollahi, S., Samadi, A., et al.[2022]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

Ruxolitinib cream 1.5% significantly improved disease severity, itching, and sleep disturbance in patients aged 12 and older with mild to moderate atopic dermatitis after 8 weeks of treatment, and continued to control symptoms for an additional 44 weeks when applied as needed.

The cream was well tolerated, with a safety profile similar to that of a placebo, and infrequent local side effects, making it a promising alternative to traditional treatments like corticosteroids for managing atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib Cream 1.5%: A Review in Mild to Moderate Atopic Dermatitis. Hoy, SM.[2023]

In two phase 3 studies involving 1249 patients with atopic dermatitis, ruxolitinib cream significantly improved treatment outcomes compared to a vehicle cream, with 93.4% of patients using the 0.75% formulation and 90.9% using the 1.5% formulation achieving clinically meaningful responses by week 8.

Patients who continued using ruxolitinib cream beyond 8 weeks showed progressive improvements, with over half achieving treatment success by week 52, indicating that extended therapy can provide additional benefits and that the cream was well tolerated throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy. Simpson, EL., Kircik, L., Blauvelt, A., et al.[2023]

Citations

1. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-new-data-phase-3b-true-ad4-trial-opzelurar

Incyte Announces New Data from Phase 3b TRuE-AD4 ... Eight-week results from the TRuE-AD4 trial demonstrate treatment with Opzelura® (ruxolitinib cream) significantly improved the clinical ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39546129/

Ruxolitinib Cream Monotherapy Improved Symptoms and ... Ruxolitinib cream improved patient-reported AD symptom burden and overall QoL by Week 2. Improvements continued or were maintained for 52 weeks.

3. jaad.org jaad.org/article/S0190-9622(25)02717-3/fulltext

Efficacy and safety of ruxolitinib cream for the treatment ... The majority of patients who applied ruxolitinib cream achieved clear or almost clear skin (IGA-CHE 0/1) accompanied by a ≥2-grade improvement ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950312425000028

Therapeutic efficacy and safety of topical ruxolitinib in mild- ... Ruxolitinib significantly improves atopic dermatitis symptoms. It is a safe and effective treatment, especially for patients with mild-to-moderate disease ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11809233/

Atopic Dermatitis Treatments Before and After Initiation of ... These 6-month follow-up data suggest that initiating ruxolitinib cream for AD may reduce the overall need for other topical treatments, oral corticosteroids, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06238817

NCT06238817 | A Study to Evaluate the Efficacy, and ... A study to evaluate the Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis ...