Ruxolitinib Cream for Eczema

(TRuE-AD4 Trial)

Recruiting at 119 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

225 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being conducted to establish the efficacy of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s.

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.

What data supports the effectiveness of the drug Ruxolitinib Cream for eczema?

Research shows that Ruxolitinib Cream significantly improved eczema symptoms like itching and skin condition in patients with mild to moderate atopic dermatitis (a type of eczema) when used for 8 weeks. It was well tolerated and provided an alternative to other topical treatments. ^{1 2 3 4 5}

Is Ruxolitinib Cream safe for use in humans?

Ruxolitinib cream has been shown to be generally safe for treating mild to moderate eczema, with side effects similar to those of a placebo cream. Some people may experience mild skin reactions like stinging or burning, but serious side effects are rare. ^{3 6 7 8 9}

How is the drug Ruxolitinib Cream different from other eczema treatments?

Ruxolitinib Cream is unique because it is a topical treatment that specifically targets Janus kinase (JAK) 1 and JAK2, which are involved in the inflammation process of eczema. This makes it an alternative to traditional treatments like corticosteroids and calcineurin inhibitors, offering a different mechanism of action to help reduce symptoms like itching and skin irritation. ^{1 2 3 4 5}

Research Team

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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]

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]

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 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]

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]

References

1. England 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. [2023]

5. England 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. [2023]

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

Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Management of Atopic Dermatitis: Clinical Utility of Ruxolitinib. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. [2023]