Efficacy and Tolerance of the Association of ANIFROLUMAB (300mg) IV Every Four Weeks and Phototherapy Versus Phototherapy in Adults With Progressive Vitiligo

Inclusion Criteria:

• Subject: male or female aged ≥ 18 years and ≤ 65 years
• Subject with body weight ≥ 40kg
• Diagnosis of non-segmental (symmetrical) vitiligo with a body surface area involved >5% excluding hands and feet
• Active non-segmental vitiligo is defined by: Non-segmental vitiligo with new patches or extension of old lesions during the last 6months AND Presence of hypochromic aspect under Wood's lamp examination and/orperifollicular hypopigmentation under Wood's lamp examination.
• Able to read, understand, and give documented (electronic or paper signature) informedconsent
• Registered in the French Social Security
• Agree to discontinue the use of the following excluded medications/treatments for atleast 4 weeks prior to randomization (Visit 2) and throughout the study: systemicsteroids, phototherapy, methotrexate, cyclosporine, mycophenolate mofetil, andazathioprine.
• Agree to discontinue the use of the following excluded medications for at least 2weeks prior to randomization (Visit 2) and throughout the study: TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus) Topicalphosphodiesterase type 4 (PDE-4) inhibitor (e.g. crisaborole) Topical JAK inhibitor (e.g.,tofacitinib or ruxolitinib) and/or any other investigational topical treatments.
• Patient characteristics
• Are male or nonpregnant, nonbreastfeeding female patients:

1. Male patients must agree to use 2 forms of birth control (1 must be highlyeffective, see below) while engaging in sexual intercourse with female partnersof childbearing potential while enrolled in the study and for at least 4 weeksfollowing the last dose of investigational product.
2. Female patients of childbearing potential must agree to use 2 forms of birthcontrol, when engaging in sexual intercourse with a male partner while enrolledin the study and for at least 12 weeks following the last dose of investigationalproduct. The following birth control methods are considered acceptable (the patient shouldchoose 2 to be used with their male partner, and 1 must be highly effective): Highly effective birth control methods: oral, injectable, or implanted hormonalcontraceptives (combined estrogen/progesterone or progesterone only, associatedwith inhibition of ovulation); intrauterine device (containing copper) orintrauterine system (e.g., progestin-releasing coil); or vasectomized male (withappropriate post vasectomy documentation of the absence of sperm in theejaculate). Effective birth control methods: condom with a spermicidal foam, gel,film, cream, or suppository; occlusive cap (diaphragm or cervical/vault caps)with a spermicidal foam, gel, film, cream, or suppository; or oral hormonalcontraceptives.
3. Females of non-childbearing potential are not required to use birth control andthey are defined as: Women ≥60 years of age or women who are congenitally sterile, or Women ≥40 and <60 years ofage who have had a cessation of menses for ≥12 months and a folliculostimulating hormone (FSH) test confirming non-childbearing potential (≥40 mIU/mL or ≥40 IU/L), or women who aresurgically sterile (i.e., have had a hysterectomy or bilateral oophorectomy or tuballigation).

• Patients fully vaccinated against COVID-19. A patient is considered fully vaccinated ≥2 weeks after receipt of the second dose in a 2-dose series (Pfizer-BioNTech andModerna).
• Signed informed consent form (ICF)

Exclusion Criteria: General exclusion criteria

• Segmental or mixed vitiligo
• Patients that are currently experiencing or have a history of other concomitant skinconditions (e.g., psoriasis or lupus erythematosus) that would interfere withevaluations of the effect of study medication on vitiligo
• Patients who are currently experiencing a skin infection that requires treatment, orwho are currently being treated with topical or systemic antibiotics.
• Patients that have any serious concomitant illness that is anticipated to require theuse of systemic corticosteroids or otherwise interfere with study participation orrequire active frequent monitoring. (e.g., unstable chronic asthma).
• Patients with history of basal cell or squamous epithelial skin cancer or melanoma
• Presence of significant uncontrolled neuropsychiatric disorder, are clinically judgedby the investigator to be at risk for suicide.
• Current alcohol, drug, or chemical abuse Exclusion criteria related to concomitant medications
• Patients that have been treated with the following therapies:

1. monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) for less than 5half-lives prior to randomization.
2. received prior treatment with any oral JAK inhibitor (e.g., tofacitinib,ruxolitinib)
3. received any systemic corticosteroid administered within 4 weeks prior to plannedrandomization or are anticipated to require systemic corticosteroids during thestudy.
4. received any systemic treatment with Methotrexate, Azathioprine, Cyclosporinewithin 12 weeks prior to planned randomization
5. have had an intra-articular corticosteroid injection within 4 weeks prior toplanned randomization.
6. have received more than 250 UV lights sessions

• Patients that are largely or wholly incapacitated permitting little or no self-care,such as being bedridden. Exclusion criteria related to infection and malignancy risk factors
• Any underlying condition that predisposes the subject to infection, including historyof/current human immunodeficiency virus (HIV) infection
• An HIV test must be performed. The result should be available within 30 days ofrandomisation, but prior to the second dose of investigational product administration (Visit 2/Week 4). Confirmed positive test for hepatitis B serology for:

1. Hepatitis B surface antigen, OR
2. Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above thelower limit of quantitation Note: Patients who were HBcAb positive at screening weretested every 3 months for HBV DNA. To remain eligible for the study, the patient's HBVDNA levels must have remained below the limit of quantitation

• Positive test for hepatitis C antibody
• Any of the following:

1. Clinically significant chronic infection (ie, osteomyelitis, bronchiectasis,etc) within 8 weeks prior to Inclusion Visit (chronic nail infections notcausing open skin lesions are allowed)
2. Any infection requiring hospitalisation or treatment with IV anti-infectivesnot completed at least 4 weeks prior to Inclusion visit

• Any infection requiring IV or oral anti-infectives (including antivirals) within 2 weeks prior to Inclusion visit
• Have evidence of active TB or latent TB:

1. have evidence of active TB, defined in this study as the following:Documented by a positive PPD test (≥5 mm induration between approximately 48and 72 hours after application, regardless of vaccination history), medicalhistory, clinical features, and abnormal chest x-ray at screening. TheQuantiFERON®-TB Gold test or TSPOT®.TB test (as available and if compliantwith local TB guidelines) may be used instead of the PPD test. Patients areexcluded from the study if the test is not negative and there is clinicalevidence of active TB. Exception: Patients with a history of active TB who have documented evidenceof appropriate treatment, have no history of re-exposure since theirtreatment was completed, and have a screening chest x-ray with no evidenceof active TB may be enrolled if other entry criteria are met. Such patientswould not be required to undergo the protocol-specific TB testing for PPD,QuantiFERON®-TB Gold test, or T-SPOT® TB test but must have a chest x-ray atscreening.
2. have evidence of untreated/inadequately or inappropriately treated latentTB, defined in this study as the following: documented to have a positivePPD test (≥5 mm induration between approximately 48 and 72 hours afterapplication, regardless of vaccination history), no clinical featuresconsistent with active TB, and a chest x-ray with no evidence of active TBat screening; or PPD test is positive and the patient has no medical historyor chest x-ray findings consistent with active TB, the patient may have aQuantiFERON®-TB Gold test or TSPOT® TB test (as available and if compliantwith local TB guidelines). If the test results are not negative, the patientwill be considered to have latent TB (for purposes of this study); orQuantiFERON®-TB Gold test or T-SPOT® TB test (as available and if compliantwith local TB guidelines) may be used instead of the PPD test. If the testresults are positive, the patient will be considered to have latent TB. Ifthe test is not negative, the test may be repeated once within approximately 2 weeks of the initial value. If the repeat test results are again notnegative, the patient will be considered to have latent TB (for purposes ofthis study). Exception: Patients who have evidence of latent TB may beenrolled if he or she completes at least 4 weeks of appropriate treatmentprior to randomization and agrees to complete the remainder of treatmentwhile in the trial. Exception: Patients with a history of latent TB who have documented evidence of appropriatetreatment, have no history of re-exposure since their treatment was completed, and have ascreening chest x-ray with no evidence of active TB may be enrolled if other entry criteriaare met. Such patients would not be required to undergo the protocol specific TB testing for PPD,QuantiFERON®-TB Gold test, or TSPOT® TB test but must have a chest x-ray at screening.

• Safety exclusions labs
• At Screening (within 4 weeks before Week 0 [Day 1]), any of the following:

1. Aspartate aminotransferase (AST) >2.0 × upper limit of normal (ULN).
2. Alanine aminotransferase (ALT) >2.0 × ULN.
3. Total bilirubin >1.5ULN (unless due to Gilbert's syndrome)
4. Serum creatinine >2.0 mg/dL (or >181 μmol/L)
5. Neutrophil count <1000/μL (or <1.0 × 109/L)
6. Platelet count <25000/μL (or <25 × 109/L)
7. Haemoglobin <8 g/dL (or <80 g/L),
8. Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjectsonly) Note: Abnormal screening laboratory tests may be repeated ONCE on aseparate sample before subject is declared a screen failure.

• Confirmed COVID-19: The Baseline Visit must be at least 14 days from onset ofsigns/symptoms or positive SARS-CoV-2 test; symptomatic subjects must have recovered,defined as resolution of fever without use of antipyretics and improvement insymptoms;
• Suspected COVID-19: Subjects with signs/symptoms suggestive of COVID-19, knownexposure, or high risk behavior should undergo molecular (e.g., polymerase chainreaction [PCR]) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure. Perioperative management of investigational productSurgery should be avoided during the study if clinically feasible, but is permitted.If a surgery becomes necessary during the study, it should be scheduled at least 4weeks after the previous administration of investigational product. For non-major surgery, the decision to withhold investigational product administration isat the Investigator's discretion. For major surgery, investigational product administration can be resumed at theInvestigator's discretion after all of the following criteria are met:
• External wound healing is complete, and
• Any postoperative antibiotic course is completed, and
• All acute surgical complications have resolved Blood donations Subjects should notdonate whole blood, blood components or sperm until the completion of the follow-upperiod. Other non-inclusion criteria
• Have hypersensitivity to anifrolumab or to any of the excipients.
• Are unable or unwilling to make themselves available for the duration of the studyand/or are unwilling to follow study restrictions/procedures.
• Are currently enrolled in any other clinical trial involving an investigationalproduct or any other type of medical research judged not to be scientifically ormedically compatible with this study.
• Have participated within the last 30 days in a clinical study involving aninvestigational product. If the previous investigational product has a long half-life (2 weeks or longer), at least 3 months or 5 half-lives (whichever is longer) should beallowed between the end of the previous treatment and the inclusion.
• Have previously been randomized in this study or any other study investigatinganifrolumab.
• Are investigator site personnel directly affiliated with this study and/or theirimmediate families. Immediate family is defined as a spouse, parent, child, orsibling, whether biological or legally adopted.