Vitiligo
Conditions
Keywords
anifrolumab, vitiligo, phototherapy, randomized
Brief summary
The purpose of this phase 2 study is to evaluate the effect and the safety of the combination of ANIFROLUMAB in combination with phototherapy in adult participants with non-segmental progressive vitiligo
Detailed description
Treatment Strategy: Multicentric, parallel double blind randomized phase 2 prospective study comparing ANIFROLUMAB (300mg/month) + narrowband UVB TL01 versus placebo + narrowband UVB TL01 Follow-up of the study: patients included in this study will start ANIFROLUMAB 3 months before starting narrowband UVB TL01. Phototherapy will be performed twice a week during 6 months. Follow-up visit will be done at week 12, 24, 36 and 48.
Interventions
DRUGAnifrolumab Infusion Product
Anifrolumab 300mg/month infusion for 36 weeks
DRUGPlacebo
Placebo once a month, infusion for 36 weeks
Sponsors
AstraZeneca
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double (Participant, Investigator) This is a double-blind study. To preserve the blinding of the study, a minimum number of sponsor personnel will see the randomization table and treatment assignments before the study is complete. All study assessments will be performed by study personnel who are blinded to the patient's treatment group. Except in clinical circumstances where unblinding is required, the patients, investigators, sponsor study team, and any personnel interacting directly with patients or investigative sites will remain blinded to Anifrolumab and placebo assignment until after completion of the Double-Blinded Treatment Period.
Intervention model description
This is a multicenter, randomized, non-comparative, phase II proof-of-concept trial involved patients with progressive vitiligo and uses one of the most common regimens in this phase of study. Assessment of the experimental treatment efficacy will be estimated only on the results obtained in the experimental treatment arm (Anifrolumab 300mg/month + narrowband UVB TL01 arm).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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 6 months AND Presence of hypochromic aspect under Wood's lamp examination and/or perifollicular hypopigmentation under Wood's lamp examination. * Able to read, understand, and give documented (electronic or paper signature) informed consent * Registered in the French Social Security * Agree to discontinue the use of the following excluded medications/treatments for at least 4 weeks prior to randomization (Visit 2) and throughout the study: systemic steroids, phototherapy, methotrexate, cyclosporine, mycophenolate mofetil, and azathioprine. * Agree to discontinue the use of the following excluded medications for at least 2 weeks prior to randomization (Visit 2) and throughout the study: TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus) Topical phosphodiesterase 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 highly effective, see below) while engaging in sexual intercourse with female partners of childbearing potential while enrolled in the study and for at least 4 weeks following the last dose of investigational product. 2. Female patients of childbearing potential must agree to use 2 forms of birth control, when engaging in sexual intercourse with a male partner while enrolled in the study and for at least 12 weeks following the last dose of investigational product. The following birth control methods are considered acceptable (the patient should choose 2 to be used with their male partner, and 1 must be highly effective): Highly effective birth control methods: oral, injectable, or implanted hormonal contraceptives (combined estrogen/progesterone or progesterone only, associated with inhibition of ovulation); intrauterine device (containing copper) or intrauterine system (e.g., progestin-releasing coil); or vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate). 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 hormonal contraceptives. 3. Females of non-childbearing potential are not required to use birth control and they are defined as: Women ≥60 years of age or women who are congenitally sterile, or Women ≥40 and \<60 years of age 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 are surgically sterile (i.e., have had a hysterectomy or bilateral oophorectomy or tubal ligation). * 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 and Moderna). * Signed informed consent form (ICF)
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Score with VASI score | Week 36 | The VASI Score is used to assess the severity and extent of Vitilgo. VASI is calculated using a formula that includes contributions from all body regions (possible range, 0-100). The body is divided into 6 separate and mutually exclusive sites (head/neck, hands, upper extremities \[excluding hands\], trunk, lower extremities \[excluding feet\], and feet), with percentage of vitiligo involvement estimated in hand units by the same investigator throughout the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score with VASI score Extent Score (VES) | Week 24 | Change in percentage of repigmented Surface area 24 weeks after-inclusion, by using the VASI score at week 24. The VASI Score is used to assess the severity and extent of Vitilgo. VASI is calculated using a formula that includes contributions from all body regions (possible range, 0-100). The body is divided into 6 separate and mutually exclusive sites (head/neck, hands, upper extremities \[excluding hands\], trunk, lower extremities \[excluding feet\], and feet), with percentage of vitiligo involvement estimated in hand units by the same investigator throughout the study. |
| Face Vitiligo Aera Scoring Index (F-VASI) score | Week 12 | Mean variation in percentage of Face Vitiligo Area Scoring Index (F-VASI) score between baseline , week 12 |
| Number of Adverse Events (AE) and serious adverse events (SAE), as well as the proportion of discontinuation due to AEs and/or SAEs | Week 36 | AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related, that occurs after a subject provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy, or require changes in the study drug. |
| Evaluation of score Vitiligo European Task Force (VETF) | Week 12 | Variation of the score Vitiligo European Task Force (VETF) The VETF score is used to assess the severity and extent of vitiligo. The VETF assesses 3 dimensions of the disease in 5 areas (Head/neck, hands and feet, trunk, arms, legs) namely 1/ extent: percentage of vitiligo involvement estimated using the rule of nines, 2/ depigmentation severity grading (stage 0: normal pigmentation Stage 1: incomplete pigmentation , stage 2 complete depigmentation, stage 3: partial hair whitening \<30% stage 4: complete hair whitening) and 3/ spreading (score O: similar limits, Score 1: progressive vitiligo; score -1: regressive vitiligo). |
| Evaluation of score of the Vitiligo Extent Score (VES) | Week 48 | Variation in percentage of the Vitiligo Extent Score (VES). The VES score is used to assess the severity and extent of vitiligo. Using the VES calculator www.vitiligo-calculator.com, investigator choose the pictures that best represent the patient's skin lesions and then the percentage of depigmented area is calculated. |
| Evaluation of score of the Vitiligo Signs of Activity Score (VSAS) | Week 12 | Variation in percentage of the Vitiligo Signs of Activity Score (VSAS). The VSAS score is used to assess the activity of the disease. It is assessed by evaluating the number of location with at least one disease sign of activity. |
| Evaluation of score of the Dermatology Life Quality Index (DLQI) Global Impression of Change-Vitiligo (PhGIC-V) | Week 12 | Variation of the score of the Dermatology Life Quality Index (DLQI). DLQI is a 10-item instrument, each item scored from 0 to 3 where higher scores correspond to worse symptom impact, full range from 0 to 30. |
| Score with VASI score | Week 12 | Change in percentage of repigmented Surface area 12 weeks after-inclusion, by using the VASI score at week 12. The VASI Score is used to assess the severity and extent of Vitilgo. VASI is calculated using a formula that includes contributions from all body regions (possible range, 0-100). The body is divided into 6 separate and mutually exclusive sites (head/neck, hands, upper extremities \[excluding hands\], trunk, lower extremities \[excluding feet\], and feet), with percentage of vitiligo involvement estimated in hand units by the same investigator throughout the study |
| Evaluation of the score of the Vitiligo Impact Patient Scale (VIP) | Week 48 | Variation of the score of the Vitiligo Impact Patient Scale (VIP). Vitiligo Impact Scale is a 12-item instrument, each item scored from 0 to 5 where higher scores correspond to worse symptom impact, full range from 0 to 145 |
| Evaluation of the Vitiligo Noticeability Scale (VNS) | Week 12 | Variation of the VNS score. The VNS is a patient-reported measure of vitiligo treatment success that is rated on a 5-point scale. The participant was asked to respond to the following query: Compared with before treatment, how noticeable is the vitiligo now? Responses: (1) more noticeable, (2) as noticeable, (3) slightly less noticeable, (4) a lot less noticeable, and (5) no longer noticeable. higher score corresponds to worse symptom impact |
| Evolution of Physician's Global Impression of Change- Vitiligo (PhGIC-V) | Week 12 | Variation of the PhGIC-V. The PhGIC-V is a physician measure of vitiligo treatment success that is rated on a 5-point scale. Overall improvement: (1) much improved, (2)minimally improved, (3)no change), (4)minimally worse, (5)much worse. Higher score corresponds to worse symptom. |
| Evolution of Patient's Global Impression of Change- Vitiligo (PaGIC-V) | Week 12 | Variation of the PaGIC-V. The PaGIC-V is a patient-reported measure of vitiligo treatment success that is rated on a 5-point scale. Overall improvement: (1) much improved, (2)minimally improved, (3)no change), (4)minimally worse, (5)much worse. Higher score corresponds to worse symptom. |
| Evolution of the Total Physician Global Vitiligo Assessment (T-PhGVA) | Week 12 | Variation fo the T-PhGVA: The T-PhGVA is a physician measure of vitiligo treatment success that is rated on a 4-point scale: overall improvement: (0) no change, (1)limited extent, (2)moderate extent, (3)extensive, (4)very extensive). Higher score corresponds to worse evaluation |
| Evaluation of blood inflammatory markers using immunofluorescence on skin biopsies and ELISA multiplex. | Day 1 | Expression of IFN-α, TNF-α, IFN-γ, IL-4, IL-5, IL-12, IL-13, IL-15, IL-17, IL-22, IL-23, IL-33 CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, CXCL16, CCL20, soluble HSP70. |
| Evaluation of the score of the Skindex 29 | Week 12 | Variation of the score of the Skindex 29. SkinDex29 is a 30-item instrument, each item scored from 1 to 5 where higher scores correspond to worse symptom impact, full range from 0 to 150. |
Countries
France
Contacts
Primary ContactJulien SENESCHAL, Prof
Backup ContactFrédéric PERRY
Outcome results
None listed