A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream Followed by an Open-Label Extension Period in Adults With Chronic Hand Eczema

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

12 Oct 2023 → 13 Dec 2024

Decision date (initial)

2023-09-11

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 evaluate the efficacy of ruxolitinib 1.5% cream versus vehicle cream in the treatment of participants with moderate to severe CHE.

Secondary objectives 6

1. To further assess the treatment effects of ruxolitinib 1.5% cream BID in participants with CHE.
2. To further evaluate the efficacy of ruxolitinib 1.5% cream BID.
3. To evaluate the participants' quality of life and other patient-reported outcomes.
4. To evaluate the safety and tolerability of ruxolitinib 1.5% cream BID.
5. To further evaluate the efficacy of ruxolitinib 1.5% cream BID.
6. To characterize biomarkers associated with CHE and/or treatment.

Conditions and MedDRA coding

Chronic Hand Eczema

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ability to comprehend and willingness to sign a written ICF for the study. A signed written ICF must be obtained for inclusion, see Section 8.1.1 (of the Protocol) for additional details.
2. Age ≥ 18 years at the screening visit.
3. Diagnosis of CHE for at least 6 months prior to screening. Diagnosis of CHE is defined as HE lasting > 3 months or ≥ 2 recurrences within the previous 12 months.
4. Screening and baseline IGA-CHE score of 3 or 4.
5. Baseline CHE-related Itch NRS score ≥ 4. Baseline Itch NRS score is defined as the 7-day average of Itch NRS score directly before Day 1 (data from a minimum of 4 out of 7 days prior to Day 1 is needed).
6. Have been treated with at least 1 prescription CHE therapy or if such therapy was not advisable or contraindicated.
7. Willingness to avoid pregnancy or fathering children, based on specific criteria (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 ruxolitinib cream and must refrain from donating sperm during this period; Female participants who are WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy test before the first application 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 ruxolitinib cream and must refrain from donating oocytes during this period).

Exclusion criteria 15

1. Known triggers for CHE (allergic or irritant, such as those identified by previous patch tests) cannot be avoided during the course of the study.
2. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol.
3. Known allergy or reaction to any of the components of the study cream.
4. In the opinion of the investigator are unable or unlikely to comply with the administration schedule and study evaluations.
5. Committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
6. Employees of the sponsor or investigator or otherwise dependents of them.
7. History of (within the past 5 years) or current AD or current psoriasis.
8. Concurrent conditions and history of other diseases: a. Other active skin disease or infection on the hands, including tinea manuum. In addition, foot eczema is excluded; b. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, or Wiskott-Aldrich syndrome); c. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline; d. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox, or impetigo) within 1 week before baseline; et al.
9. 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 drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. Examples: a. Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months from Day 1 of study drug application, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mm Hg) unless approved by the medical monitor/sponsor; b. Participants with or a history of malignancy in the 5 years preceding the baseline visit, except for adequately treated nonmetastatic nonmelanoma skin cancer; c. Current and/or history of arterial or venous thrombosis, including deep venous thrombosis and pulmonary embolism; d. Current and/or history of active tuberculosis or current and/or history of latent tuberculosis unless adequately treated; e. History of severe anemia, severe thrombocytopenia, or severe neutropenia.
10. Particular clinical laboratory test results at screening: a. Cytopenias, defined as follows: Hemoglobin < 100 g/L (ie, 10 g/dL), Absolute neutrophil count < 1.5 × 109/L (ie, 1500/μL), Platelet count < 1 × 1011/L (ie, 100,000/μL) b. Liver function tests: AST or ALT ≥ 2.5 × ULN, Total bilirubin > 1.5 × ULN unless Gilbert syndrome; et al. (specified in the Study Protocol, section 5.2. Exclusion Criteria, page 28).
11. Use of particular treatments within the indicated washout period before the baseline visit: a. 12 weeks or 5 half-lives, whichever is longer – biologic agents (eg, dupilumab). For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor. b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs; cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus); or oral alitretinoin or any other systemic treatment for CHE. c. 4 weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, baricitinib, brepocitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, upadacitinib). d. 2 weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. e. 2 weeks – systemic antibiotics, immunizations with live-attenuated vaccines, or sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). f. 1 week – use of any topical treatments for CHE (other than bland emollients, eg, Aveeno® creams, ointments, sprays, and soap substitutes), such as corticosteroids, calcineurin inhibitors, topical antipruritics (eg, doxepin cream), phosphodiesterase 4 inhibitors, coal tar (shampoo), topical antibiotics or antifungals, and antibacterial cleansing body wash/soap.
12. Psoralen ultraviolet A or ultraviolet B therapy for CHE within 4 weeks before baseline.
13. Pregnant or lactating participants or those considering pregnancy during the period of their study participation.
14. 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.
15. In the EU, participants considered incapacitated (according to CTR Article 31) are excluded from the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving IGA-CHE-TS at Week 16.

Secondary endpoints 15

1. Proportion of participants achieving ITCH4 response at Week 16, Proportion of participants achieving ITCH4 response at Week 4, Proportion of participants achieving ITCH4 response at Week 1 (Day 7).
2. Proportion of participants achieving IGA-CHE-TS at each postbaseline visit.
3. Proportion of participants achieving ITCH4 response at Day 3.
4. Change from baseline in CHE-related Itch NRS score at each postbaseline visit.
5. Time to ≥ 4-point improvement from baseline in CHE-related Itch NRS score.
6. Change from baseline in CHE-related Skin Pain NRS score at each postbaseline visit.
7. Proportion of participants achieving ≥ 2-point improvement in CHE related Skin Pain NRS score from baseline to Week 16.
8. Time to ≥ 2-point improvement from baseline in CHE-related Skin Pain NRS score.
9. Percentage change in HECSI from baseline to Week 16.
10. PGIC score at each postbaseline visit.
11. Change from baseline in DLQI score at Weeks 2, 4, 8, 12, 16, 24, and 32.
12. Change from baseline in EQ-5D-5L score at Weeks 2, 4, 8, 12, 16, 24, and 32.
13. Change from baseline in QOLHEQ score at Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up.
14. Change from baseline in WPAI-ChHD score at Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up.
15. The type, frequency, and severity of AEs as well as changes in vital signs and laboratory data for hematology and serum chemistry.

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

2 EU/EEA countries · 10 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

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

Application history

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