A Phase 3b, Double-Blind, Multicenter, Randomized, Vehicle-Controlled, Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

13 Aug 2024 → 17 Oct 2025

Decision date (initial)

2024-08-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 TCSs and TCIs.

Secondary objectives 4

1. To further assess the treatment effects of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to TCSs and TCIs.
2. To evaluate the safety and tolerability of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to TCSs and TCIs.
3. To further evaluate the efficacy of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to TCSs and TCIs.
4. To evaluate quality of life and other PROs in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to TCSs and TCIs.

Conditions and MedDRA coding

Atopic Dermatitis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

In accordance with Incyte's Clinical Trial Transparency and Data Sharing Policy.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adults aged ≥ 18 years at screening.
2. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria.
3. AD duration of at least 2 years.
4. IGA score of 3 at screening and Day 1.
5. EASI score > 7 at screening and Day 1.
6. Itch NRS score ≥ 4 at Day 1, defined as the average of the 7 days directly before Day 1, with Itch NRS values available for at least 4 of the 7 days.
7. %BSA (excluding the scalp) with AD involvement of at least 10% and up to 20% at screening and Day 1.
8. DLQI score > 10 at screening and Day 1.
9. Documented recent history (within 12 months before the screening visit) of inadequate response, intolerance, or contraindication to TCSs and TCIs (as stated in Section 6.6.1 in the protocol).
10. Agree to discontinue all agents used to treat AD from screening through the final follow-up visit, except as outlined in Section 6.6.2 and Section 6.6.3 of the protocol.
11. Willingness to avoid pregnancy, breastfeeding, or fathering children based on the criteria below. Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 90 days (a spermatogenesis cycle) after the last application of study cream and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed. Female participants who are WOCBP must not be lactating or breastfeeding and have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first application of study cream on Day 1 and must agree to take appropriate precautions to avoid pregnancy from screening through 30 days (1 menstrual cycle) after the last application of study cream and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy should be communicated to the participants and their understanding confirmed. Female participants not considered to be of childbearing potential are eligible.
12. Ability to comprehend and willingness to sign an ICF.

Exclusion criteria 16

1. Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to Day 1.
2. Concurrent conditions and history of other diseases as follows: Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome); Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before Day 1; Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox) within 1 week before Day 1; 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, etc.
3. 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. For example: Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months before Day 1; New York Heart Association Class III or IV congestive heart failure; or arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mmHg) unless approved by the medical monitor/sponsor; History of malignancy in the 5 years preceding Day 1, except for adequately treated, nonmetastatic, nonmelanoma skin cancer; Current and/or history of arterial or venous thrombosis, including deep venous thrombosis and pulmonary embolism, etc.
4. Any of the following clinical laboratory test results at screening: Hemoglobin < 10 g/dL, Liver function tests: AST or ALT ≥ 2 × ULN, Alkaline phosphatase > 1.5 × ULN, Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) with the exception of Gilbert's disease, etc.
5. Use of any of the following treatments within the indicated washout period before Day 1: 5 half-lives or 12 weeks, whichever is longer: biologic agents. For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor; 4 weeks: systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive (eg, JAK inhibitors) or immunomodulating agents (eg, mycophenolate or tacrolimus); 2 weeks or 5 half-lives, whichever is longer - strong systemic CYP3A4 inhibitors, etc.
6. History of treatment failure with any systemic or topical JAK inhibitor (eg, ruxolitinib, tofacitinib, baricitinib, abrocitinib, upadacitinib) for AD or any other inflammatory condition.
7. Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 2 weeks prior to the baseline visit and/or intention to have such exposure during the study that is thought by the investigator to potentially impact the participant's AD.
8. History of alcoholism or drug addiction within 1 year before screening or current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the administration schedule and study assessments.
9. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before baseline with another investigational medication or current enrollment in another investigational drug Protocol.
10. Removed during Protocol Amendment 1.
11. Known allergy or reaction to any component of the study cream formulation.
12. In the opinion of the investigator, are unable or unlikely to comply with the administration schedule, study evaluations, and procedures (eg, eDiary compliance).
13. Committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
14. Employees of the sponsor, sponsor delegates (eg, contract research organizations), or investigator or are otherwise dependents of them.
15. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.
16. In the EU, participants considered incapacitated (according to CTR Article 31).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants with EASI75 from baseline at Week 8. (EASI75 is defined as achieving ≥ 75% improvement in EASI score.) and Proportion of participants with IGA-TS at Week 8. (IGA-TS is defined as achieving an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline.)

Secondary endpoints 4

1. Proportion of participants with ITCH4 from baseline to Week 8. (ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.) and Proportion of participants with ITCH4 from baseline to Day 7. and Proportion of participants with ITCH4 from baseline to Day 3. and Proportion of participants with ITCH4 from baseline to Day 2.
2. The type, frequency, and severity of AEs as well as changes from baseline in vital signs and laboratory data for hematology and serum chemistry.
3. Proportion of participants with EASI75 from baseline at each postbaseline visit except Week 8. and Proportion of participants with IGA-TS from baseline at each postbaseline visit except Week 8. and Proportion of participants with ITCH4 from baseline at each postbaseline visit except Week 8. and Time to achieve ITCH4 during the VC period. and ime to achieve ITCH2 during the VC period. (ITCH2 is defined as achieving ≥ 2-point improvement from baseline in Itch NRS score.) etc.
4. Proportion of participants who achieve ≥ 4-point improvement in DLQI from baseline at each postbaseline visit. and Change from baseline in the following scores at each postbaseline visit: − DLQI − POEM − EQ-5D-5L − HADS − PROMIS Short Form – Sleep-Related Impairment (8a – 7-day recall) − PROMIS Short Form – Sleep Disturbance (8b – 7-day recall) and Change from baseline score at Weeks 8 and 24 in WPAI-AD.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 5

Locations

9 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 126 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications