A Double-Blind, Randomized, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream in Participants With Prurigo Nodularis

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], Diseases [C] - Immune System Diseases [C20]

Trial duration

15 Feb 2024 → 4 Nov 2025

Decision date (initial)

2024-01-29

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: Safety, Efficacy

To demonstrate the efficacy of ruxolitinib 1.5% cream BID in participants with PN.

Secondary objectives 1

1. To further demonstrate the treatment effects of ruxolitinib 1.5% cream BID in participants with PN.

Conditions and MedDRA coding

Prurigo Nodularis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Ability to comprehend and willingness to sign a written ICF for the study. Note: A signed written ICF must be obtained for inclusion, see Section 8.1.1 for additional details.
2. Age ≥ 18 years at the time of signing the ICF.
3. Clinical diagnosis of PN ≥ 3 months before screening.
4. There are ≥ 6 pruriginous lesions on ≥ 2 different body areas (such as right and left leg) at screening and baseline. Note: The total estimated BSA treatment area must be ≤ 20%.
5. IGA-CPG-S score of ≥ 2 at screening and baseline.
6. Baseline PN-related WI-NRS score ≥ 7. Baseline WI-NRS score is defined as the 7-day average of WI-NRS scores before Day 1 (data from a minimum of 4 out of 7 days prior to Day 1 is needed).
7. Removed during Protocol Amendment 2.
8. Willingness to avoid pregnancy or fathering children based on the criteria below. a. 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 (see Appendix A) should be communicated to the participants and their understanding confirmed. b. Female participants who are WOCBP must have a negative serum pregnancy test at screening and 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 (see Appendix A) should be communicated to the participants and their understanding confirmed. c. A female participant not considered to be of childbearing potential as defined in Appendix A is eligible.

Exclusion criteria 21

1. Acute or chronic pruritus due to a condition other than PN. (Conditions such as: scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous disease, excoriation syndrome, venous stasis; systemic hematologic disorders [iron-deficiency anemia, polycythemia rubra vera, lymphoma, leukemia]; gastrointestinal disorders [celiac disease, gastric malignancy, obstructive biliary disease; α-1 antitrypsin deficiency]; infections [HIV, hepatitis B and C, mycobacterial]; endocrine disorders [hyperthyroidism]; psychosocial disorders [depression, anxiety], and chronic renal failure.)
2. Total estimated BSA treatment area (excluding the scalp) > 20%.
3. Neuropathic and psychogenic pruritus, such as but not limited to notalgia paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or delusional parasitosis.
4. Active AD lesions (signs and symptoms other than dry skin) within 6 months of screening and baseline.
5. Uncontrolled hypothyroidism or hyperthyroidism at screening as determined by the investigator. Note: If the participant has a history of thyroid disease and is on treatment, the participant must be on a stable thyroid regimen for at least 6 weeks prior to Day 1.
6. Concurrent conditions and history of other diseases: a. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton's syndrome), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of pruriginous lesions or assessments of efficacy or compromise participant safety. b. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, 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, clinically infected AD, or impetigo) within 1 week before baseline. e. Unstable asthma or COPD requiring systemic treatment (such as intravenous steroids) or hospital admission or treatment in the emergency department within 3 months of baseline or Stable asthma or COPD requiring the dose equivalent of budesonide more than 720 µg/day (2 puffs BID of a 180-μg dose) or fluticasone more than 440 μg/day (2 puffs BID of a 110-μg dose) or other equivalent inhaled corticosteroids. f. Acute or chronic active HBV or HCV infection (see Section 8.4.5.3). Participants who have recovered or have been successfully treated with no evidence of active HBV or HCV infection and those who are immune due to HBV vaccination can enroll. g. Any underlying condition known to be associated with the clinical presentation of PN that is not under control (stable) prior to the baseline visit.
7. 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 application of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. For example: a. Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction or stroke within 6 months from Day 1, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mmHg) 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 vein 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.
8. Any of the following clinical laboratory test results at screening: a. Cytopenias, defined as follows: − Hemoglobin < 100 g/L (ie, 10 g/dL) − Absolute neutrophil count < 1.5 × 10 9 /L (ie, 1500/µL) − Platelet count < 1 × 10 11 /L (ie, 100,000/µL) b. Liver function tests: − AST or ALT ≥ 2.5 × ULN − Total bilirubin > 1.5 × ULN unless Gilbert's syndrome c. Estimated glomerular filtration rate < 30 mL/min/1.73 m 2 (using the CKD-EPI 2021 Creatinine Equation). d. Positive serology test results at screening for HIV antibody. e. Any other clinically significant laboratory result that, in the opinion of the investigator, poses a significant risk to the participant.
9. Use of any of the following treatments within the indicated washout period before the baseline visit: a. Five half-lives or 12 weeks, whichever is longer – biologic agents (eg, dupilumab). For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor. b. 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. c. Four weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, baricitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, or upadacitinib). d. Four weeks – systemic or intralesional corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus). e. Four weeks for opioid antagonists (eg, naloxone and naltrexone). f. Four weeks for gabapentin, pregabalin, or thalidomide. g. Four weeks for the following: − Paroxetine, fluvoxamine, or other SSRIs − SNRIs − Tricyclic antidepressants h. Four weeks – recreational or medicinal use (topical, inhaled, oral, sublingual, or any other route) of cannabis or cannabinoids (eg, THC, CBD). i. Two weeks – systemic antibiotics and immunizations with live-attenuated vaccines. j. Note: Live-attenuated vaccines are prohibited during the DBVC period. COVID-19 vaccination is permitted. k. Two weeks – sedating antihistamines. l. Two weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. m. Two weeks – any topical treatments for PN (other than bland emollients, eg, Aveeno ® creams, ointments, sprays, and soap substitutes), such as corticosteroids, calcineurin inhibitors, topical antipruritics (eg, doxepin cream), PDE4 inhibitors, coal tar (shampoo), topical antibiotics, and antibacterial cleansing body wash/soap. n. One week – nonsedating antihistamines used for the treatment of PN.
10. Current use of a medication known to cause pruritus.
11. History of treatment failure (as assessed by the investigator through study participant interview) for PN or any inflammatory condition with any systemic or topical JAK inhibitors (eg, abrocitinib, baricitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, or upadacitinib).
12. Psoralen and ultraviolet A or ultraviolet B therapy within 4 weeks before baseline or Ultraviolet light therapy or prolonged exposure to natural or artificial sources of ultraviolet radiation (eg, sunlight or tanning booth) within 2 weeks before baseline and/or intention to have such exposure during the study that is thought by the investigator to potentially impact the participant's PN.
13. Pregnant or lactating, or considering pregnancy during 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 application schedule and study assessments.
15. Removed during Protocol Amendment 1.
16. Known allergy or reaction to any of the components of the study cream.
17. In the opinion of the investigator, unable or unlikely to comply with the application schedule and study evaluations.
18. Committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
19. Employees of the sponsor or investigator or otherwise dependents of them.
20. The following participants are excluded in France: a. Vulnerable populations according to article L.1121-6 of the French Public Health Code. b. Adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code. c. Individuals not affiliated with the social security system.
21. 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. WI-NRS4 response at Week 12, defined as achieving a ≥ 4-point improvement (reduction) in WI-NRS score from baseline.

Secondary endpoints 4

1. WI-NRS4 response at Week 4.
2. Overall-TS at Week 12, defined as achieving both a WI-NRS4 response and an IGA-CPG-S TS. (IGA-CPG-S-TS is defined as an IGA-CPG-S score of 0 or 1 with a ≥ 2 grade improvement from baseline)
3. IGA-CPG-S-TS at Week 12.
4. WI-NRS4 response on Day 7.

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 6

Locations

8 EU/EEA countries · 41 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 166 files

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

Application history

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