Evaluation of AMG 714 for Vitiligo (REVEAL)

Evaluation of AMG 714 for Vitiligo: A Phase 2a Randomized Double Blind Placebo Controlled Trial (ITN086AI)

This study is designed to evaluate the efficacy of AMG 714 for the treatment of adult participants with vitiligo.

Study Overview

Detailed Description

The primary objective of this trial is to determine the efficacy of interleukin-15 (IL-15) inhibition with AMG 714 at inducing facial repigmentation in vitiligo.

The secondary objectives are to:

-Evaluate the safety and tolerability of AMG 714 in vitiligo- -Determine the efficacy of IL-15 inhibition with AMG 714 at inducing total body skin repigmentation in vitiligo-

  • Assess the durability of the skin repigmentation achieved by AMG 714 in vitiligo, and
  • Evaluate the efficacy of AMG 714 followed by narrow band UVB (nbUVB) phototherapy.

Study Type

Interventional

Enrollment (Anticipated)

57

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California, Irvine: Department of Dermatology
        • Contact:
        • Principal Investigator:
          • Anand Ganesan, MD, PhD
      • Sacramento, California, United States, 95816
        • Recruiting
        • University of California Davis Health System: Department of Dermatology
        • Principal Investigator:
          • Victor Huang, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06824
        • Recruiting
        • Yale University School of Medicine: Department of Dermatology
        • Contact:
        • Principal Investigator:
          • Brett A. King, MD, PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center: Department of Dermatology
        • Contact:
        • Principal Investigator:
          • David Rosmarin, MD
      • Worcester, Massachusetts, United States, 01605
        • Recruiting
        • University of Massachusetts Medical School
        • Contact:
        • Principal Investigator:
          • Medhi Rashighi
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Contact:
        • Principal Investigator:
          • Iltefat Hamzavi, MD
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health
        • Principal Investigator:
          • George Han
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • Perelman School of Medicine, University of Pennsylvania: Department of Dermatology
        • Principal Investigator:
          • Susan C. Taylor, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Individuals must meet all of the following criteria to be eligible for enrollment as study participants:

  1. Adults 18-75 years of age.
  2. Clinical diagnosis of active or stable vitiligo made by a dermatologist, as defined in Section 3.4.2.
  3. F-VASI ≥ 0.25 (Appendix 2).
  4. T-VASI ≥ 3 (Appendix 2).
  5. Completion of SARS-CoV-2 primary vaccination series ≥ 14 days prior to randomization (Day 0).
  6. Willingness to:

    1. Undergo nbUVB phototherapy, as outlined in Section 7.3.
    2. Stop all other treatments for vitiligo from screening through the final follow up visit as outlined in Section 7.2.

Exclusion Crieteria:

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

  1. Inability or unwillingness of a participant to give written informed consent or comply with the study protocol.
  2. Segmental vitiligo.
  3. Contraindication to nbUVB phototherapy.
  4. More than 33% leukotrichia on the face or on the total body.
  5. Use of biologic immunosuppressive or immunomodulatory agents, or investigational therapy or procedure within 12 weeks or 5 half-lives prior to Visit 0 (whichever is longer), except agents authorized for prevention and treatment of SARS-CoV-2 infection according to FDA Emergency Use Authorization (EUA).
  6. Use of laser or light-based treatment (phototherapy) including tanning beds within 8 weeks prior to Visit 0.
  7. Use of non-biologic systemic or topical immunosuppressive or immunomodulatory agents within 4 weeks prior to Visit 0.
  8. History of melanocyte-keratinocyte transplantation procedure (MKTP) or other surgical treatment for vitiligo.
  9. Current or past use of the depigmenting agent monobenzyl ether of hydroquinone, including Benoquin® (Monobenzone).
  10. Presence of skin conditions or lesions that would confound the vitiligo assessments.
  11. Spontaneous repigmentation within 6 months prior to Visit 0 (repigmentation without any treatment and significant in amount as determined by the investigator).
  12. Uncontrolled thyroid function at screening as determined by the investigator. If the participant has a history of thyroid disease and is on treatment, the participant must be on a stable thyroid regimen for at least three months prior to Visit 0.
  13. Greater than 3 adequately treated nonmetastatic basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) within 12 months prior to Visit 0; or previous history of multiple BCC or SCC which may pose additional risks from participation in the study in the opinion of the investigator.
  14. Previous or current diagnosis of other cancer, except adequately treated cervical carcinoma in situ.
  15. Acute or chronic infection, including current use of suppressive therapy for chronic infection, hospitalization for treatment of infection within 90 days prior to Visit 0, or parenteral anti-microbial (including anti-bacterial, anti-viral, or anti-fungal agents) use within 90 days prior to Visit 0.
  16. Evidence of infection, including:

    1. Human immunodeficiency virus (HIV)
    2. Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb
    3. Current or prior hepatitis C (HCV), unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 12 weeks after cessation of therapy)
    4. Positive Quantiferon-TB Gold or Quantiferon-TB Gold Plus test. PPD or T-SPOT.TB test may be substituted for Quantiferon-TB Gold or Quantiferon-TB Gold Plus test
  17. Any of the following laboratory abnormalities:

    1. White blood count (WBC) < 3.5 x 103/μL
    2. Hemoglobin < 10 g/dL
    3. Platelets (Plt) < 125,000/mm3
    4. Alanine aminotransferase (ALT) ≥ 2x ULN
    5. Aspartate aminotransferase (AST) ≥ 2x ULN
  18. Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception or be sexually inactive by abstinence until study Week 48 (Section 7.4). Contraception or abstinence is required for 2 weeks prior to Visit 0.
  19. Women who are pregnant or lactating.
  20. Vaccination with a live attenuated vaccine within 30 days prior to Visit 0.
  21. Known drug allergy or reaction to any component of AMG 714 (Section 6.1.1) or proteins derived from mammalian cell lines.
  22. Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
  23. Current, diagnosed mental illness (e.g. severe depression) or current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

Completion of a SARS-CoV-2 vaccination series is required for all participants prior to randomization (Section 4.2). Booster immunizations are strongly recommended for all participants eligible to receive them.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AMG 714
Participants will be administered 300 mg AMG 714 subcutaneously on Day 0 and every 2 weeks thereafter through week 10 (for a total of 6 doses).
anti-IL-15 monoclonal antibody (Anti-IL-15 MAB)
Participants will undergo narrow band ultraviolet B (nbUVB) phototherapy if their total body Vitiligo Area Scoring Index (T-VASI) does not improve by ≥ 25% at Week 24 compared to Week 0. Phototherapy will be administered in accordance with the Vitiligo Working Group expert recommendations.
Other Names:
  • narrow band ultraviolet B phototherapy
Placebo Comparator: Placebo
Participants will be administered 300 mg AMG 714 subcutaneously on Day 0 and every 2 weeks thereafter through week 10 (for a total of 6 doses).
Participants will undergo narrow band ultraviolet B (nbUVB) phototherapy if their total body Vitiligo Area Scoring Index (T-VASI) does not improve by ≥ 25% at Week 24 compared to Week 0. Phototherapy will be administered in accordance with the Vitiligo Working Group expert recommendations.
Other Names:
  • narrow band ultraviolet B phototherapy
Placebo for AMG 714

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 24
Time Frame: Week 24
≥35% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 12, Week 36, Week 48
Time Frame: Week 12, Week 36, Week 48
≥35% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 12, Week 36, Week 48
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥25 (F-VASI25) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥25% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥50 (F-VASI50) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥50% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥75 (F-VASI75) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥75% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥90 (F-VASI90) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥90% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥25 (T-VASI25) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥ 25% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥35 (T-VASI35) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥ 35% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥50 (T-VASI50) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥ 50% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥75 (T-VASI75) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥ 75% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
Week 12, Week 24, Week 36, Week 48
Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥90 (T-VASI90) at Week 12, Week 24, Week 36 and Week 48
Time Frame: Week 12, Week 24, Week 36, Week 48
≥ 90% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
Week 12, Week 24, Week 36, Week 48
Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The Face Vitiligo Area Scoring Index (F-VASI) measures the amount of depigmented vitiligo skin expressed as a percentage of the total area of skin on the face (100%), measured by a clinician using the palmar method.
Week 12, Week 24, Week 36, and Week 48
Change from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The total body Vitiligo Area Scoring Index (T-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). Assessments are conducted by a clinician.
Week 12, Week 24, Week 36, and Week 48
Change from Baseline (Day 0) in Vitiligo Extent Score (VES) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The Vitiligo Extent Score (VES) is a measurement of the overall vitiligo involvement of the body (extent) and is used by clinicians for the assessment of disease activity. Methodology: Using the VES calculator ( www.vitiligo-calculator.com) , the clinician chooses the pictures that best represent the participant's skin lesions, then the percentage of depigmented area is calculated.
Week 12, Week 24, Week 36, and Week 48
Change from Baseline (Day 0) in the Vitiligo Quality of Life (VitiQoL) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The Vitiligo Quality of Life instrument (VitiQoL) is a validated instrument comprised of sixteen questions on a 7 point Likert scale that asks participants to rate aspects of their vitiligo during the past month (Range for each question: An answer of "Not at all" to "All of the Time.").
Week 12, Week 24, Week 36, and Week 48
Change from Baseline (Day 0) in the Vitiligo Noticeability Scale (VNS) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48

The Vitiligo Noticeability Scale (VNS) is a validated patient-reported outcome measure of vitiligo treatment.

Participants will be shown a pre-treatment photograph of their face and asked to answer the question, "Compared with before treatment, how noticeable is the vitiligo now?" There are five Response Options (Score). Success criteria are pre-defined.

Week 12, Week 24, Week 36, and Week 48
Percentage Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The Face Vitiligo Area Scoring Index (F-VASI) measures the percentage of depigmented vitiligo skin expressed as a percentage of the total area of skin on the face (100%), measured by a clinician using the palmar method.
Week 12, Week 24, Week 36, and Week 48
Percentage Change from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI) at Week 12, Week 24, Week 36, and Week 48
Time Frame: Week 12, Week 24, Week 36, and Week 48
The total body Vitiligo Area Scoring Index (T-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). Assessments are conducted by a clinician.
Week 12, Week 24, Week 36, and Week 48
Occurrence of ≥ Grade 2 Adverse Events (AEs)
Time Frame: Up to Week 48
Includes all ≥ Grade 2 untoward or unfavorable medical occurrence(s) associated with investigational product administration and/ or any study mandated procedures.
Up to Week 48
Occurrence of ≥ Grade 3 Infectious Adverse Events (AEs)
Time Frame: Up to Week 48
Includes all ≥ Grade 3 infectious untoward or unfavorable medical occurrence(s).
Up to Week 48

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve total body Vitiligo Area Scoring Index ≥35 (T-VAS135)
Time Frame: Up to 48 Weeks

Participants who achieve ≥ 35% improvement in full body assessment of Vitiligo Area and Severity Index (T-VASI). The time-to-event data will be summarized using the Kaplan-Meier method.

The T-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). Assessments are conducted by a clinician.

Up to 48 Weeks
EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve a F-VASI35
Time Frame: Up to 48 Weeks

Participants who achieve ≥ 35% improvement in Face Vitiligo Area Scoring Index (F-VASI) score. The time-to-event data will be summarized using the Kaplan-Meier method.

The F-VASI measures the amount of depigmented vitiligo skin expressed as a percentage of the total area of skin on the face (100%), measured by a clinician using the palmar method.

Up to 48 Weeks
EXPLORATORY: AMG 714 Serum Levels
Time Frame: Week 6, Week 12
Level of study product AMG 714 measured in the blood (serum) of participants.
Week 6, Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Brett A. King, MD, PhD, Yale University School of Medicine: Department of Dermatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2020

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

September 1, 2024

Study Registration Dates

First Submitted

April 6, 2020

First Submitted That Met QC Criteria

April 6, 2020

First Posted (Actual)

April 8, 2020

Study Record Updates

Last Update Posted (Actual)

April 20, 2023

Last Update Submitted That Met QC Criteria

April 19, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • DAIT ITN086AI
  • NIAID CRMS ID#: 38677 (Other Identifier: DAIT NIAID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participant level data access and additional relevant materials will be made available upon completion of the trial.

IPD Sharing Time Frame

After completion of the trial, within 24 months status post database lock.

IPD Sharing Access Criteria

The Immunology Database and Analysis Portal (ImmPort) is an open access platform for research data sharing and a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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