Study to Evaluate Adverse Events and Change in Disease Activity With Oral Tablets of Upadacitinib in Adult Participants With Non-Segmental Vitiligo

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects With Non-Segmental Vitiligo

Vitiligo is a common chronic autoimmune disease that causes the body's immune system to attack its own pigment producing skin cells. This study is to evaluate how safe and effective upadacitinib is in participants with non-segmental vitiligo. Adverse effects and change in disease activity will be assessed.

Upadacitinib is being evaluated for the treatment of non-segmental vitiligo. The study will enroll approximately 160 participants aged 18-65 with non-segmental vitiligo in 5 treatment arms across 35 sites worldwide.

Participants will either receive study drug vs placebo oral tablets once daily (QD) for 24 weeks (Period A). In Period B (up to 52 weeks), participants who received placebo during the first 24 weeks will switch to study drug. Participants who received study drug during the first 24 weeks, will continue to receive study drug.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Completed
• Conditions: Non-Segmental Vitiligo
• Intervention / Treatment: Drug: Placebo; Drug: Upadacitinib

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr. Chih-ho Hong Medical Inc. /ID# 228403
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Wiseman Dermatology Research /ID# 228410
  • Ontario
    • Toronto, Ontario, Canada, M4W 2N4
      • Research Toronto /ID# 228401
    • Waterloo, Ontario, Canada, N2J 1C4
      • Duplicate_K. Papp Clinical Research /ID# 228877
  • Quebec
    • Québec, Quebec, Canada, G1V 4X7
      • Centre de Recherche dermatologique du Quebec Metropolitain /ID# 228388
• France
  • Creteil, France, 94000
    • Duplicate_Hopital Henri Mondor /ID# 228198
  • Toulouse, France, 31400
    • CHU Toulouse - Hopital Larrey /ID# 228196
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06200
      • Chu de Nice-Hopital Larchet Ii /Id# 228192
  • Gironde
    • Bordeaux, Gironde, France, 33075
      • Duplicate_Hopital Saint-Andre /ID# 228193
  • Rhone
    • Lyon, Rhone, France, 69003
      • HCL - Hopital Edouard Herriot /ID# 228194
• Japan
  • Aichi
    • Nagoya shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital /ID# 228725
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8602
      • Nippon Medical School Hospital /ID# 230361
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital /ID# 230288
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 230362
  • Yamanashi
    • Kofu-shi, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital /ID# 229441
• United States
  • California
    • Irvine, California, United States, 92697-1385
      • University of California Irvine /ID# 229390
    • Redwood City, California, United States, 94063
      • Stanford University /ID# 228000
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Clearlyderm Dermatology /ID# 227993
    • Miami, Florida, United States, 33165-3372
      • New Horizon Research Center /ID# 229403
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology, PA /ID# 229400
    • Tampa, Florida, United States, 33613-1244
      • ForCare Clinical Research /ID# 228010
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin, LLC /ID# 227996
  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1552
      • Tufts Medical Center /ID# 228087
    • Worcester, Massachusetts, United States, 01655
      • Duplicate_UMass Chan Medical School /ID# 228066
  • Michigan
    • Clarkston, Michigan, United States, 48346
      • Duplicate_Michigan Center for Research Company /ID# 228054
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology /ID# 228056
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research /ID# 229401
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137-2842
      • Essential Medical Research, LLC /ID# 228074
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center /ID# 228007
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center /ID# 228073
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Duplicate_Medical University of South Carolina /ID# 228067
  • Tennessee
    • Murfreesboro, Tennessee, United States, 37130-2450
      • International Clinical Research - Tennessee LLC /ID# 228059
  • Texas
    • Bellaire, Texas, United States, 77401
      • Bellaire Dermatology Associates /ID# 228004
    • Houston, Texas, United States, 77030-1501
      • University of Texas Health Science Center at Houston /ID# 229399
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research, Inc. /ID# 228050

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of non-segmental vitiligo (NSV) and no segmental or localized vitiligo.

• Participants with all of the following at Screening and Baseline.

  • Visits: ≥ 0.5 F-VASI and ≥ 5 total vitiligo area scoring index (T-VASI).
  • Participants who have had prior exposure to immunomodulatory biologic therapy, for any indications, but discontinued the biologic therapy prior to the first dose of study drug. Recommended washout periods for biologic therapies include ≥ 4 weeks for etanercept; ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and ixekizumab; ≥ 16 weeks for secukinumab; and ≥ 12 weeks for ustekinumab. For biologic therapies not specified, therapies must be discontinued at least 5 times the mean terminal elimination half-life of a drug or 3 months prior to Baseline, whichever is longer.

Exclusion Criteria:

• Participants with segmental or localized vitiligo.
• Participants with other skin conditions that would interfere with evaluation of vitiligo, participants with uncontrolled thyroid disease, and participants with > 33% leukotrichia on the face or > 33% leukotrichia on the body (including face).
• Participants previously treated with any topical or systemic janus kinase (JAK) inhibitor or permanent skin bleaching agents.
• Participants treated with any systemic vitiligo therapy (e.g., methotrexate, mycophenolate mofetil, corticosteroids), supplemental vitiligo therapy (antioxidants/vitamins/herbal medicine/traditional Chinese medicine), and/or topical vitiligo therapy including permanent or temporary tattoos within a minimum of 30 days prior to the first dose of study drug (Note: Camouflage and makeup may be used).
• Participants treated with any phototherapy, including excimer (or other forms of laser therapy), within a minimum of 12 weeks prior to the first dose of study drug.
• Participants have history of malignancy other than successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.
• Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery;
• History of an organ transplant which requires continued immunosuppression;
• History of gastrointestinal (GI) perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment;
• Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded;
• Uncontrolled thyroid disease;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upa 22 mg Period 1, then Upa 22 mg Period 2; Participants received upadacitinib 22 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 22 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2.	Drug: Upadacitinib; Oral tablets; Other Names: RINVOQ; ABT-494
Experimental: Upa 11 mg Period 1, then Upa 11 mg Period 2; Participants received upadacitinib 11 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 11 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2.	Drug: Upadacitinib; Oral tablets; Other Names: RINVOQ; ABT-494
Experimental: Upa 6 mg Period 1, then Upa 6 mg Period 2; Participants received upadacitinib 6 mg administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 6 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2.	Drug: Upadacitinib; Oral tablets; Other Names: RINVOQ; ABT-494
Experimental: Placebo Period 1, then Upa 22 mg Period 2; Participants received Placebo for upadacitinib administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 22 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2.	Drug: Placebo; Oral tablets; Drug: Upadacitinib; Oral tablets; Other Names: RINVOQ; ABT-494
Experimental: Placebo Period 1, then Upa 11 mg Period 2; Participants received Placebo for upadacitinib administered orally once a day (QD) as tablets for 24 weeks during Period 1. Participants then received upadacitinib 11 mg administered orally once a day (QD) as tablets for 28 weeks during Period 2.	Drug: Placebo; Oral tablets; Drug: Upadacitinib; Oral tablets; Other Names: RINVOQ; ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Facial-Vitiligo Area Scoring Index (F-VASI) at Week 24	The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving F-VASI 75 (≥ 75% Improvement in F-VASI From Baseline) at Week 24	The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease.	Baseline, Week 24
Percentage of Participants Achieving F-VASI 50 (≥ 50% Improvement in F-VASI From Baseline) at Week 24	The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. The F-VASI includes contributions from the face, with a possible range from 0 to 3, with higher scores indicating more severe disease.	Baseline, Week 24
Percentage of Participants Achieving Total Vitiligo Area Scoring Index (T-VASI) 50 (≥ 50% Improvement in T-VASI From Baseline) at Week 24	The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area [BSA]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease.	Baseline, Week 24
Percent Change From Baseline in T-VASI at Week 24	The vitiligo area scoring index (VASI) is a validated scoring method used to assess the areas of depigmentation due to vitiligo. It is based on a composite estimate of the overall area of vitiligo patches, measured by the number of hand units (palm plus 5 digits = 1% body surface area [BSA]) multiplied by the degree of depigmentation within each affected area (0%, 10%, 25%, 50%, 75%, 90%, or 100%). The T-VASI is calculated using a formula that includes contributions from all body regions, with a possible range from 0 to 100, with higher scores indicating more severe disease. Negative changes from baseline indicate improvement.	Baseline, Week 24
Change From Baseline in the Vitiligo Quality-of-Life (VitiQoL) Instrument Total Score at Week 24	The VitiQoL is a validated questionnaire used in clinical trials to assess stigma-related vitiligo impacts. The VitiQoL uses subject-elicited social, affective, and behavior items, asking the subject's appraisal of the vitiligo-related impacts over the last month. Fifteen items are scored on a 7-point scale ranging from 0 ("Not at all") to 6 ("All of the time"). Item scores (0 to 6) are summed to provide a total score range of 0 to 90; higher scores indicate greater impairment of quality of life (QoL). Negative changes from baseline indicate improvement.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): August 29, 2023

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Upadacitinib; Vitiligo; RINVOQ; ABT-494; Non-segmental vitiligo (NSV)
• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hypopigmentation; Vitiligo; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M19-051; 2021-000081-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes