Ruxolitinib Cream for Prurigo Nodularis

(TRuE-PN2 Trial)

Recruiting at 100 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: Psoralen, Ultraviolet therapy

Disqualifiers: Chronic pruritus, Active dermatitis, 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: Unknown

190 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety and tolerability of a cream for people with Prurigo Nodularis, a condition with itchy skin nodules. The cream works by blocking enzymes that cause inflammation and itching. It has been previously tested for its effects in conditions like atopic dermatitis.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are using any prohibited medications, a washout period may be required.

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

The trial protocol mentions that certain medications are prohibited unless a washout period (time without taking certain medications) is completed. It is best to discuss your current medications with the trial team to see if they are allowed.

What data supports the idea that Ruxolitinib Cream for Prurigo Nodularis is an effective treatment?

The available research shows that Ruxolitinib Cream is effective for treating atopic dermatitis, a condition similar to Prurigo Nodularis. In studies, patients using Ruxolitinib Cream had significant improvements in skin condition and itchiness compared to those using a placebo cream. For example, in one study, 93.4% of patients using Ruxolitinib Cream showed improvement, compared to 69% using the placebo. This suggests that Ruxolitinib Cream could also be effective for Prurigo Nodularis, as both conditions involve similar symptoms like itchiness and skin irritation. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Ruxolitinib Cream for Prurigo Nodularis?

Ruxolitinib cream has shown effectiveness in reducing symptoms like itchiness and improving skin condition in patients with atopic dermatitis, a condition with similar symptoms to prurigo nodularis. In studies, patients using ruxolitinib cream experienced significant improvements compared to those using a placebo cream. ^{1 2 3 4 5}

What safety data is available for Ruxolitinib Cream?

Ruxolitinib Cream, also known as Opzelura, has been evaluated for safety in various studies. In phase III trials for atopic dermatitis, it was well tolerated with a safety profile similar to vehicle cream, showing infrequent application site adverse events like stinging or burning. A review of 24 studies involving 2618 patients across different dermatologic conditions found minimal bioavailability and low rates of mild-to-moderate treatment-related adverse events, indicating a favorable safety profile. Additionally, systemic administration of ruxolitinib has rare skin toxicity, and carcinogenicity studies in animals showed no increased incidence of neoplastic findings, suggesting it is not carcinogenic. ^{1 6 7 8 9}

Is Ruxolitinib Cream safe for use in humans?

Ruxolitinib cream has been shown to be generally safe in humans, with studies indicating it is well tolerated for conditions like atopic dermatitis, vitiligo, and psoriasis. Mild skin reactions like stinging or burning are infrequent, and there are no significant safety concerns related to its use as a topical treatment. ^{1 6 7 8 9}

Is Ruxolitinib Cream a promising drug for treating Prurigo Nodularis?

Yes, Ruxolitinib Cream is a promising drug. It has shown significant improvements in skin conditions like atopic dermatitis, reducing itchiness and improving quality of life. It is well-tolerated and offers a safer alternative to other treatments. ^{1 2 3 5 6}

How is ruxolitinib cream different from other drugs for prurigo nodularis?

Ruxolitinib cream is unique because it is a topical formulation that targets Janus kinase (JAK) 1 and JAK2, which are involved in inflammation, offering a potentially safer alternative to systemic treatments with fewer side effects. This makes it different from traditional treatments like corticosteroids, which can have more systemic side effects. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for individuals with Prurigo Nodularis who've had it for at least 3 months, have a significant itch score (≥7), and more than six itchy lesions across two body areas. Participants must not be pregnant or planning to become so and should not have used certain medications recently.

Inclusion Criteria

Do you have lesions on 2 or more different body areas (such as the right and left leg)?

Baseline PN-related WI-NRS score ≥ 7

I have been diagnosed with peripheral neuropathy for at least 3 months.

Exclusion Criteria

Individuals not affiliated with the social security system

I am able to give my consent and am not under legal protection.

Use of any protocol-defined prohibited medication unless a washout is completed or use of medication known to cause itching

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants apply ruxolitinib or vehicle cream to affected areas twice daily for 12 weeks

12 weeks

Regular visits for assessment

Open-Label Extension

Participants who completed the double-blind period continue treatment with ruxolitinib cream for up to 40 weeks

40 weeks

Regular visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ruxolitinib Cream
• Vehicle Cream

Trial Overview The study tests Ruxolitinib cream's effectiveness in reducing itching and improving skin condition compared to a placebo cream (Vehicle Cream). It aims to determine how safe and tolerable the medication is for people with Prurigo Nodularis.

Participant Groups

Group I: Ruxolitinib 1.5% Cream Experimental Treatment 1 Intervention

Participants apply ruxolitinib 1.5% cream topically to the affected areas as a thin film BID for 12 weeks during the DBVC period. Participants who have completed the treatment during DBVC period will enter the open label extension (OLE) period for up to 40 weeks.

Group II: Vehicle Cream Placebo Group 1 Intervention

Participants apply ruxolitinib matching vehicle cream topically to the affected areas as a thin film twice daily (BID) for 12 weeks during the DBVC period. Participants who have completed the treatment during DBVC period will enter the open label extension (OLE) period for up to 40 weeks.

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

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]

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]

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 phase II clinical trials, patients using 1.5% topical ruxolitinib (RUX) showed a significant improvement in Eczema Area and Severity Index (EASI) scores after 4 weeks, with a mean improvement of 71.6% compared to only 15.5% for the placebo group (P < 0.001).

Phase III trials demonstrated that a higher percentage of patients treated with 0.75% and 1.5% topical RUX achieved clear or almost clear skin (IGA score of 0 or 1) after 8 weeks, significantly outperforming the placebo (15.1% and 7.6% respectively, P < 0.001), indicating its efficacy in managing atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Ruxolitinib in the Treatment of Atopic Dermatitis. Mohney, LA., Singh, R., Feldman, SR.[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]

Topical ruxolitinib has been shown to improve various dermatological conditions, including atopic dermatitis, vitiligo, psoriasis, and lichen planus, based on a review of 24 studies involving 2618 patients.

The safety profile of topical ruxolitinib is favorable, with minimal bioavailability and low rates of mild-to-moderate side effects, making it a more tolerable option compared to systemic Janus kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of Topical Ruxolitinib in Dermatology: A Review. Kashetsky, N., Turchin, I.[2023]

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, a JAK1 and JAK2 inhibitor used for myelofibrosis and polycythemia vera, showed no carcinogenic potential in long-term studies with Tg.rasH2 mice and Sprague-Dawley rats, indicating it does not increase cancer risk.

Despite some pharmacological effects like lymphoid depletion and inflammation, ruxolitinib did not affect survival rates or increase neoplastic findings, suggesting it is safe for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. Shuey, DL., Oliver, J., Zhou, G., et al.[2021]

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]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Review of Ruxolitinib in the Treatment of 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. Canada pubmed.ncbi.nlm.nih.gov

Utilization of Topical Ruxolitinib in Dermatology: A Review. [2023]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. [2021]

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

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