Safety and Efficacy of ARQ-252 Cream 0.3% in Subjects With Non-Segmental Facial Vitiligo

Exclusion Criteria

• •Subjects who have ever used skin bleaching treatments for treatment of vitiligo or other pigmented areas, eg, depigmenting agents such as monobenzyl ether of hydroquinone, including Benoquin® (Monobenzone)
• •Use of any other prior and concomitant therapy that is a contraindication to phototherapy or may otherwise interfere with the objective of the study as per discretion of the Investigator, such as drugs that cause photosensitivity or skin pigmentation (eg, antibiotics such as tetracyclines, antifungals) within 8 weeks of Baseline (Visit 2).
• •More than 33% leukotrichia in facial lesions (assessed via dermatoscope).
• •Other forms of vitiligo (eg, segmental vitiligo); or other skin depigmentation disorder that would confound study assessments.
• •Use of oral or systemic immunomodulating medications (eg, corticosteroids, azathioprine, methotrexate, cyclosporine) within 8 weeks of Baseline (Visit 2).
• •Use of prescription or over-the-counter topical treatments that may affect vitiligo (eg, corticosteroids, tacrolimus/pimecrolimus, retinoids, vitamin D derivates, psoralens) within 4 weeks prior to Baseline (Visit 2).
• •Use of any biological or experimental therapy for vitiligo within 24 weeks of Baseline (Visit 2) (or 5 half-lives, whichever is longer).
• •Use of phototherapy (including laser and tanning beds) within 8 weeks prior to Baseline (Visit 2).
• •Previous oral or topical JAK inhibitor therapy within 24 weeks prior to Baseline (Visit 2), and/or prior non-response to oral or topical JAK inhibitor therapy for vitiligo
• •History of melanocyte-keratinocyte transplantation procedure (MKTP) or other surgical treatment for vitiligo.
• •Contraindication to phototherapy, such as photosensitivity disorder (eg, lupus, polymorphic light eruption, solar urticaria, dermatomyositis) or use of photosensitizing or phototoxic medications.
• •Subjects with clinically significant abnormal thyroid-stimulating hormone or free T4 at screening, or otherwise uncontrolled thyroid function at screening as determined by the investigator (Note: If the subject has a history of thyroid disease and is on treatment, the participant must be on a stable thyroid regimen for at least 3 months prior to baseline)
• •History of chronic alcohol or drug abuse within 6 months prior to baseline.
• •Subjects with a cytopenia at screening, defined as follows: Leukocytes \< 3 × 10\^9/L (2.5 × 10\^9/L for subjects who are African-American), Neutrophils \< lower limit of normal (\<1.5x10\^9/L), Lymphocytes \< 0.8 × 10\^9/L, Hemoglobin \< 10 g/dL, Platelets \< 100 × 10\^9/L.
• •Subjects with current or a history of non-skin cancer within 5 years with the exception carcinoma in situ of the cervix.
• •Subjects with greater than 3 adequately treated nonmetastatic basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) within 12 months prior to Baseline (Visit 2), or a previous history of multiple BCC or SCC on any area of the body, which may pose additional risks from participation in the study, in the opinion of the Investigator.
• •Subjects with previous history of melanoma anywhere on the body, or basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or actinic keratosis (AK) on the face, neck, hands, forearms, or elbows.
• •Subjects that have received live vaccine therapy less than 4 weeks prior Baseline (Visit 2), or anticipate receiving a live or live-attenuated vaccination during the course of the study, have received immunosuppressive drugs less than 4 weeks prior Baseline, or have known infection with mycobacterium tuberculosis, hepatitis B or C, or HIV, or have a diagnosis of an immunodeficiency disorder.
• •Subject had a major surgery within 4 weeks prior to Baseline or has a major surgery planned during the study.
• •Subjects with severe renal insufficiency (as evidenced by estimated glomerular filtration rate \<40 mL/min) or with severely impaired liver function (Child-Pugh Class C), ALT or AST ≥ 2 × ULN, total bilirubin \> 1.5 x ULN, or total bilirubin \> ULN and ≤ 1.5 x ULN AND direct bilirubin is \> 35% of total bilirubin, ALP ≥ 2x ULN
• •Subjects with known or suspected hypersensitivity to component(s) of the investigational product.
• •Pregnant or lactating women or women planning to become pregnant during the study and / or within 28 days following the last dose of investigational product.
• •Subjects who cannot discontinue the use of strong systemic Cytochrome P-450 CYP3A4 inducers e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, rifampin and carbamazepine for 2 weeks prior to Baseline and during the study period.
• •Subjects who cannot discontinue the use of strong systemic Cytochrome P-450 CYP3A4 inhibitors e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, fluconazole, nefazodone, saquinavir, suboxone and telithromycin for 2 weeks prior to Baseline and during the study period.