Evaluation of AMG 714 for Vitiligo

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

Detailed Description
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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.

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

Conditions
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Vitiligo

Intervention / Treatment
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* Biological: AMG 714
* Biological: Placebo
* Procedure: nbUVB phototherapy


Participation Criteria
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Eligibility Criteria
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Individuals must meet all of the following criteria to be eligible for enrollment as study participants: Adults 18-75 years of age. Clinical diagnosis of active or stable vitiligo made by a dermatologist, as defined in Section 3.4.2. F-VASI ≥ 0.25 (Appendix 2). T-VASI ≥ 3 (Appendix 2). Completion of SARS-CoV-2 primary vaccination series ≥ 14 days prior to randomization (Day 0). Willingness to: Undergo nbUVB phototherapy, as outlined in Section 7.3. 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: Inability or unwillingness of a participant to give written informed consent or comply with the study protocol. Segmental vitiligo. Contraindication to nbUVB phototherapy. More than 33% leukotrichia on the face or on the total body. 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). Use of laser or light-based treatment (phototherapy) including tanning beds within 8 weeks prior to Visit 0. Use of non-biologic systemic or topical immunosuppressive or immunomodulatory agents within 4 weeks prior to Visit 0. History of melanocyte-keratinocyte transplantation procedure (MKTP) or other surgical treatment for vitiligo. Current or past use of the depigmenting agent monobenzyl ether of hydroquinone, including Benoquin® (Monobenzone). Presence of skin conditions or lesions that would confound the vitiligo assessments. Spontaneous repigmentation within 6 months prior to Visit 0 (repigmentation without any treatment and significant in amount as determined by the investigator). 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. 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. Previous or current diagnosis of other cancer, except adequately treated cervical carcinoma in situ. 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. Evidence of infection, including: Human immunodeficiency virus (HIV) Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb 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) 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 Any of the following laboratory abnormalities: White blood count (WBC) < 3.5 x 103/μL Hemoglobin < 10 g/dL Platelets (Plt) < 125,000/mm3 Alanine aminotransferase (ALT) ≥ 2x ULN Aspartate aminotransferase (AST) ≥ 2x ULN 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. Women who are pregnant or lactating. Vaccination with a live attenuated vaccine within 30 days prior to Visit 0. Known drug allergy or reaction to any component of AMG 714 (Section 6.1.1) or proteins derived from mammalian cell lines. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 2a, double blind, placebo-controlled, multi-center, proof of concept trial of AMG 714 for the treatment of vitiligo. Participants will be randomized 2:1 to receive AMG 714 or placebo for AMG714. Random assignment will be stratified by active versus stable vitiligo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 714<br>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). | Biological: AMG 714<br>* anti-IL-15 monoclonal antibody (Anti-IL-15 MAB)<br>Procedure: nbUVB phototherapy<br>* 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.<br>* Other names: narrow band ultraviolet B phototherapy;|
| Placebo Comparator: Placebo<br>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). | Biological: Placebo<br>* Placebo for AMG 714<br>Procedure: nbUVB phototherapy<br>* 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.<br>* Other names: narrow band ultraviolet B phototherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at 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 | ≥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 | ≥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 | ≥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 | ≥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 | ≥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 | ≥ 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 | ≥ 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 | ≥ 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 | ≥ 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 | ≥ 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | Includes all ≥ Grade 3 infectious untoward or unfavorable medical occurrence(s). | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, facial repigmentation, randomized placebo-controlled phase 2a trial