Study of Efficacy, Safety and Tolerability of Crisaborole and PF-07038124 With and Without NBUVB in Vitiligo

Study Overview
=================
Brief Summary
-----------------
This is a phase 2A clinical trial designed to test the pro-melanogenic and anti-inflammatory role of phosphodiesterase-4 inhibitors (PDE4i), alone and in combination with active narrow band UVB (NBUVB), in vitiligo lesions. This is a double-blind, randomized controlled trial (RCT) with six study arms. The goal is for 64 participants to be recruited and complete the study.

Official Title
-----------------
Study of Efficacy, Safety and Tolerability of Crisaborole and PF-07038124 With and Without NBUVB in Vitiligo: A Phase 2A Randomized, Double-Blind, Vehicle-Controlled Clinical Trial

Conditions
-----------------
Vitiligo

Intervention / Treatment
-----------------
* Drug: Crisaborole 2 % Topical Ointment
* Drug: PF-07038124 0.01% topical ointment
* Device: NBUVB phototherapy
* Device: Sham phototherapy
* Drug: Vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Active or stable non-segmental vitiligo at Screening and Baseline visits: A clinical diagnosis of non-segmental vitiligo (vitiligo vulgaris or acrofacial vitiligo) for at least 3 months, AND Body Surface Area affected (BSA) involvement 3%-90%, excluding involvement of scalp, palms of the hands, soles of the feet, AND BSA >= 0.25% involvement of the facial area, AND Minimum Facial Vitiligo Area Scoring Index (F-VASI) >=0.25% and Total VASI >=3% Must agree that the treatment area will involve 3%-25% BSA If receiving concomitant medication for any reason other than vitiligo, must be on a stable regimen (no new drug or dosage changes within 7 days of baseline visit) and willing to remain on stable regimen for duration of the study Must agree to stop all other treatments for vitiligo from screening through 1 week after discontinuation of study drug treatment Must be capable of giving signed informed consent and comply with the requirements and restrictions as listed in the informed consent document and protocol Must agree to avoid exposure to the sun as much as possible and not to use tanning booths, sun lamps, or other ultraviolet light sources other than requested by the study team during the study Exclusion Criteria: Pregnant or breastfeeding females Females of childbearing potential who are unwilling or unable to use contraception for the duration of the study and for at least 28 days after the last dose of study intervention Other types of vitiligo that do not meet criteria for active or stable or non-segmental vitiligo, including segmental, mucosal, focal, and mixed vitiligo, and those with vitiligo universalis Active forms of other hypo- or depigmentation, as detailed in the protocol Active forms of inflammatory skin disease(s) associated with hypo- or depigmentation at the time of screening or baseline that, in the opinion of the investigator, would interfere with evaluation of vitiligo or response to treatment Leukotrichia in more than 33% of the facial area affected with vitiligo lesions OR leukotrichia in more than 33% of the total BSA affected with vitiligo lesions History of transplantation procedure for vitiligo at any point History of any skin bleaching treatment for vitiligo or other dermatoses at any point Active acute or chronic skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to first drug application (baseline), OR superficial skin infections within 2 weeks prior to first drug application (NOTE: MAY BE RESCREENED AFTER INFECTION RESOLUTION) Known history of severe allergic or anaphylactoid reaction to any PDE4 inhibitors or lidocaine Documented lack of response to prior PDE4 inhibitor therapy Presence of other severe, progressive, or uncontrolled diseases, including but not limited to renal, hepatic, cardiac, pulmonary, endocrine, immunological/rheumatological, hematological, gastrointestinal, metabolic, neurologic, psychiatric, immunodeficiency (including HIV positive serology), OR significant laboratory abnormalities that would increase risk associated with study participation or interfere with interpretation of study results, or in the opinion of the investigator, the participant is inappropriate for entry into the study, or unwilling/unable to comply with protocol-specified assessments and lifestyle considerations Any malignancies or history of skin malignancies, excluding adequately treated or excised non-metastatic basal cell or squamous cell skin cancer, or cervical carcinoma in situ Significant trauma or major surgery 1 month prior to screening or considered in imminent need of surgery during the study Alcohol or substance abuse within 6 months of screening that in the opinion of the investigator would preclude participation or adherence in the study Previous administration of an investigational drug or vaccine occurring within 30 days preceding the first application of study drug used in this study Any biologic or immune-modulating agent (including oral JAK inhibitors, PDE4i, other immunosuppressive agents such as oral corticosteroids, calcineurin inhibitors, azathioprine, mycophenolate mofetil) requires a washout period of 8 weeks before screening and through the final safety follow-up visit Any topical treatment (such as topical steroids, calcineurin inhibitors, vitamin D analogs, JAK inhibitors, PDE4i) requires a washout period of 2 weeks before screening visit and through the final safety follow-up visit Ultraviolet light exposure, including UVB/UVA/PUVA delivered by booth/excimer laser, or tanning bed exposure, requires a washout period of 8 weeks before screening and through the final safety follow-up visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active NBUVB plus Crisaborole 2% topical ointment<br>12 participants will receive 6 months of treatment with crisaborole 2% topical along with 6 months of treatment with active NBUVB | Drug: Crisaborole 2 % Topical Ointment<br>* Twice daily crisaborole 2% topical ointment<br>* Other names: Eucrisa;Device: NBUVB phototherapy<br>* Home narrow band UVB phototherapy exposure sessions 3 times per week<br>* Other names: Narrow band UVB;|
| Experimental: Active NBUVB plus PF-07038124 0.01% topical ointment<br>12 participants will receive 6 months of treatment with active NBUVB, to be combined with 3 months of treatment with PF-07038124 0.01% topical ointment followed by 3 months of vehicle ointment | Drug: PF-07038124 0.01% topical ointment<br>* Twice daily PF-07038124 0.01% topical ointment<br>Device: NBUVB phototherapy<br>* Home narrow band UVB phototherapy exposure sessions 3 times per week<br>* Other names: Narrow band UVB;Drug: Vehicle<br>* Twice daily vehicle ointment<br>|
| Active Comparator: Active NBUVB plus vehicle ointment<br>8 participants will receive 6 months of treatment with active NBUVB combined with 6 months of vehicle ointment application | Device: NBUVB phototherapy<br>* Home narrow band UVB phototherapy exposure sessions 3 times per week<br>* Other names: Narrow band UVB;Drug: Vehicle<br>* Twice daily vehicle ointment<br>|
| Experimental: Sham phototherapy plus crisaborole 2% topical ointment<br>12 participants will receive 6 months of treatment with crisaborole 2% topical ointment combined with 6 months of sham phototherapy | Drug: Crisaborole 2 % Topical Ointment<br>* Twice daily crisaborole 2% topical ointment<br>* Other names: Eucrisa;Device: Sham phototherapy<br>* Non-NBUVB visible light radiation exposure sessions 3 times per week<br>|
| Experimental: Sham phototherapy plus PF-07038124 0.01% topical ointment<br>12 participants will receive 3 months of treatment with PF-07038124 0.01% topical ointment, followed by 3 months of vehicle ointment, along with 6 months of sham phototherapy | Drug: PF-07038124 0.01% topical ointment<br>* Twice daily PF-07038124 0.01% topical ointment<br>Device: Sham phototherapy<br>* Non-NBUVB visible light radiation exposure sessions 3 times per week<br>Drug: Vehicle<br>* Twice daily vehicle ointment<br>|
| Placebo Comparator: Sham phototherapy plus vehicle ointment<br>8 participants will receive 6 months of sham phototherapy combined with 6 months of vehicle ointment application | Device: Sham phototherapy<br>* Non-NBUVB visible light radiation exposure sessions 3 times per week<br>Drug: Vehicle<br>* Twice daily vehicle ointment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving at 50% or greater improvement from baseline in facial Vitiligo Area Scoring Index (F)-VASI | Assessment of facial repigmentation via changes in depigmented areas | 6 months (week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving 90% or greater improvement from baseline in F-VASI |  | 6 months (week 24) | 
| Proportion of participants achieving 50% or greater improvement from baseline in total (T)-VASI |  | 6 months (week 24) | 
| Proportion of participants achieving a Vitiligo Noticeability Scale (VNS) rating of a lot less noticeable or no longer noticeable |  | 6 months (week 24) | 
| Percentage change from baseline in facial segment of Body Surface Area affected (F-BSA) |  | 6 months (24 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitiligo, PDE-4 inhibitor, Phototherapy, Repigmentation