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

• ClinicalTrials.gov Identifier: NCT05298033
• Recruitment Status: Recruiting
• First Posted: March 28, 2022
• Last Update Posted: September 15, 2022
• Sponsor: University of Colorado, Denver
• Collaborator: Pfizer
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vitiligo	Drug: Crisaborole 2 % Topical Ointment; Drug: PF-07038124 0.01% topical ointment; Device: NBUVB phototherapy; Device: Sham phototherapy; Drug: Vehicle	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 7, 2022
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active NBUVB plus Crisaborole 2% topical ointment; 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; Twice daily crisaborole 2% topical ointment; Other Name: Eucrisa; Device: NBUVB phototherapy; Home narrow band UVB phototherapy exposure sessions 3 times per week; Other Name: Narrow band UVB
Experimental: Active NBUVB plus PF-07038124 0.01% topical ointment; 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; Twice daily PF-07038124 0.01% topical ointment; Device: NBUVB phototherapy; Home narrow band UVB phototherapy exposure sessions 3 times per week; Other Name: Narrow band UVB; Drug: Vehicle; Twice daily vehicle ointment
Active Comparator: Active NBUVB plus vehicle ointment; 8 participants will receive 6 months of treatment with active NBUVB combined with 6 months of vehicle ointment application	Device: NBUVB phototherapy; Home narrow band UVB phototherapy exposure sessions 3 times per week; Other Name: Narrow band UVB; Drug: Vehicle; Twice daily vehicle ointment
Experimental: Sham phototherapy plus crisaborole 2% topical ointment; 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; Twice daily crisaborole 2% topical ointment; Other Name: Eucrisa; Device: Sham phototherapy; Non-NBUVB visible light radiation exposure sessions 3 times per week
Experimental: Sham phototherapy plus PF-07038124 0.01% topical ointment; 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; Twice daily PF-07038124 0.01% topical ointment; Device: Sham phototherapy; Non-NBUVB visible light radiation exposure sessions 3 times per week; Drug: Vehicle; Twice daily vehicle ointment
Placebo Comparator: Sham phototherapy plus vehicle ointment; 8 participants will receive 6 months of sham phototherapy combined with 6 months of vehicle ointment application	Device: Sham phototherapy; Non-NBUVB visible light radiation exposure sessions 3 times per week; Drug: Vehicle; Twice daily vehicle ointment

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants achieving at 50% or greater improvement from baseline in facial Vitiligo Area Scoring Index (F)-VASI [ Time Frame: 6 months (week 24) ]
   Assessment of facial repigmentation via changes in depigmented areas

Secondary Outcome Measures :

1. Proportion of participants achieving 90% or greater improvement from baseline in F-VASI [ Time Frame: 6 months (week 24) ]
2. Proportion of participants achieving 50% or greater improvement from baseline in total (T)-VASI [ Time Frame: 6 months (week 24) ]
3. Proportion of participants achieving a Vitiligo Noticeability Scale (VNS) rating of "a lot less noticeable" or "no longer noticeable" [ Time Frame: 6 months (week 24) ]
4. Percentage change from baseline in facial segment of Body Surface Area affected (F-BSA) [ Time Frame: 6 months (24 weeks) ]

Other Outcome Measures:

1. Quantification of pigment via Fontana-Masson staining [ Time Frame: Baseline (day 0, pre-treatment) and 3 months (12 weeks) ]
   Molecular outcome: using skin biopsies treated with PDE4i with/without active NBUVB
2. Assessment of melanocyte population expansion via immunohistochemistry (IHC) studies [ Time Frame: Baseline (day 0, pre-treatment) and 3 months (12 weeks) ]
   Molecular outcome: using skin biopsies treated with PDE4i with/without active NBUVB
3. Assessment of percent change from baseline in serum key inflammatory chemokines [ Time Frame: Baseline (pre-treatment) and at 3 months (12 weeks) and 6 months (24 weeks) ]
   Molecular outcome: using samples for serum measurements of IFN-gamma, IL-15, CXCL-9, CXCL-10, which have been implicated in vitiligo pathogenesis

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 >= 0.5% involvement of the facial area, AND
• Minimum Facial Vitiligo Area Scoring Index (F-VASI) >=0.5% 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

Contacts and Locations

Contacts

Contact: Stanca Birlea, MD; 720-202-7162; stanca.birlea@cuanschutz.edu

Contact: Torunn E Sivesind, MD; 916-474-9963; torunn.sivesind@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Anschutz - Clinical and Translational Research Centers; Recruiting

Aurora, Colorado, United States, 80045

Contact: Diane Branham, RN, MBA 720-848-7901 diane.branham@uchealth.org

Sponsors and Collaborators

University of Colorado, Denver

Pfizer

Investigators

• Principal Investigator: Stanca Birlea, MD; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT05298033
• Other Study ID Numbers: 21-4837
• First Posted: March 28, 2022
• Last Update Posted: September 15, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by University of Colorado, Denver:

Vitiligo; PDE-4 inhibitor; Phototherapy; Repigmentation

Additional relevant MeSH terms:

Vitiligo; Hypopigmentation; Pigmentation Disorders; Skin Diseases