Topical Ruxolitinib Evaluation in Immune-related Lichenoid Skin-Toxicities

Phase 2

Not yet recruiting

• Conditions: Exanthema; Lichenoid Skin Rashes Under Anti-PD1 Tumor Therapy
• Interventions: Drug: Ruxolitinib Topical Cream

• Registration Number: NCT06399029
• Lead Sponsor: University of Zurich

Brief Summary

Skin rash during tumor treatment with immunotherapy (anti-PD1 antibody therapy) is a common side effect. If patients suffer from such a skin reaction, they typically suffer from a rash on the chest, back and extremities. The skin reaction is usually treated with cortisone in cream or tablet form. There is already research in humans on the skin reaction under anti-PD1 antibody therapy. Previous studies in humans have shown that certain inflammatory markers are elevated. It is also know that the study drug can help to reduce these inflammatory markers. However, there is currently not enough data available whether the study drug can actually reduce inflammation in the skin in a rash under anti-PD1 antibody therapy. The investigators are therefore examining in this study whether the study drug is effective and well tolerated in a skin rash under anti-PD1 antibody therapy. The study drug contains the active ingredient ruxolitinib and is applied as a cream. The study drug is approved for other skin diseases (vitiligo and atopic eczema) in the USA and in countries of the European Union (EU). Approval in Switzerland is still pending. Only once the efficacy of the study drug against skin rashes under anti-PD1 antibody therapy has been scientifically investigated and proven can it be approved and used as a therapy in Switzerland. In this study, the participants are not divided into groups. Each study patient receives the test substance.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-25
• Study First Submitted QC: 2024-04-30
• Study First Posted: 2024-05-03
• Status Verified: 2024-06
• Study Start: 2024-06
• Last Update Submitted: 2024-06-11
• Last Update Posted: 2024-06-12
• Primary Completion: 2025-11
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Adult patients eligible for this inclusion in this study have to fulfil all the following criteria:

• Indication: lichenoid skin toxicities / rash developed under/after anti-programmed cell death protein-1 therapy (anti-PD-1 therapy)
• Male and female patients, age ≥ 18 years
• Patients that are able to speak and read German or English.
• The subject was informed and gave his/her consent to the Institutional Review Boards (IRB)/Independent Ethics Committee (IEC) -approved informed consent

Exclusion Criteria

Patients fulfilling any of the following criteria are not eligible for the inclusion in this study:

• Patient suffering other skin disease resembling lichenoid skin lesions under anti-PD-1 therapy.

• Acute psychiatric illness or acute crisis.

• Contraindications to ruxolitinib, e.g. known hypersensitivity or allergy

• Topical glucocorticosteroids, topical calcineurin inhibitors, UV light therapy, therapeutic biologics, other Janus kinase inhibitors (JAK inhibitors) or potent immunosuppressants such as azathioprine or cyclosporine are not allowed during the study or for 8 weeks before the study beginning.

• Women who are pregnant or breast feeding *

• Intention to become pregnant during the course of the study

• Known or suspected non-compliance, drug or alcohol abuse.

• Patients with an active, serious infection, including localized infections.

• Inability to follow the procedures of the study due to language problems, psychological disorders, dementia of the participant.

• Participation in another study with topical or oral ruxolitinib within the 30 days preceding and during the present study.

• Previous enrolment into the current study.

• Enrolment of the investigator, his/her family members, employees and other dependent persons.

  • Participants must avoid pregnancy during the study. A blood pregnancy test is required before start of therapy, with regular urine tests throughout. Lactating individuals are ineligible.

Participants must use effective contraceptives, either:

• An ovulation-inhibiting method (e.g., pill, injectable, implant, patch, or vaginal ring) or
• An intrauterine device (IUD).
• Contraception should extend one week post-study. If pregnancy occurs during or within one week after the study, participants should notify the overseeing physician immediately.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Intervention	Ruxolitinib Topical Cream	This study will be performed as one-arm with no comparator.

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving at least 90% improvement of rash at week 12.	week 12	The improvement of rash is defined on the physician global assessment score (PGA) and on the body surface area (BSA).; PGA: measures the overall response to treatment as assessed by the physician; scale 0-4; Reduction of PGA (e.g. PGA 4 to PGA0) will be converted into percentage: decrease of PGA of 1 point on a scale from 0 to 4 shows a decrease of 25%, decrease of 4 points shows a decrease of 100%.; This value (percentage of PGA decrease) will be combined with the reduction of BSA (percentage) and will result in the improvement of rash.

Secondary Outcome Measures

Name	Time	Method
Proportion of patient reported outcome: Treatment Satisfaction Questionnaire for Medication (TSQM)	baseline, week 2, 4, 8 and 12	Treatment Satisfaction Questionnaire for Medication (TSQM): The TSQM is a questionnaire used to measure patient satisfaction with medication. The score ranges from 0 to 100 points
Proportion of patients achieving 50% improvement of rash at week 12.	week 12	The improvement of rash is defined on the physician global assessment score (PGA) and on the body surface area (BSA).; PGA: measures the overall response to treatment as assessed by the physician; scale 0-4; Reduction of PGA (e.g. PGA 4 to PGA0) will be converted into percentage: decrease of PGA of 1 point on a scale from 0 to 4 shows a decrease of 25%, decrease of 4 points shows a decrease of 100%.; This value (percentage of PGA decrease) will be combined with the reduction of BSA (percentage) and will result in the improvement of rash.
Proportion of patient reported outcome: Itch Numerical Rating Scale (Itch NRS)	baseline, week 2, 4, 8 and 12	Itch Numerical Rating Scale (Itch NRS): 2 questions, rating the itch intensity on a scale from 0 to 10 points
Percentage change from body surface area at baseline to week 2, 4, 8 and 12	baseline, week 2, 4, 8 and 12	Calculation of the affected body surface area as a percentage.
Proportion of patients achieving 75% improvement of rash at week 12.	week 12	The improvement of rash is defined on the physician global assessment score (PGA) and on the body surface area (BSA).; PGA: measures the overall response to treatment as assessed by the physician; scale 0-4; Reduction of PGA (e.g. PGA 4 to PGA0) will be converted into percentage: decrease of PGA of 1 point on a scale from 0 to 4 shows a decrease of 25%, decrease of 4 points shows a decrease of 100%.; This value (percentage of PGA decrease) will be combined with the reduction of BSA (percentage) and will result in the improvement of rash.
Proportion of patient reported outcome: Dermatology Life Quality Index (DLQI)	baseline, week 2, 4, 8 and 12	Dermatology Life Quality Index (DLQI): 10 questions, summing the score of each question resulting in a minimum of 0 and a maximum of 30 points
Proportion of patient reported outcome: Five Well-Being Index (WHO-5)	baseline, week 2, 4, 8 and 12	Five Well-Being Index (WHO-5): a short self-reported measure of current mental wellbeing. It consists of five statements, which respondents rate according to a scale between 0 to 5