Evaluation of AMG 714 for Vitiligo

National Institute of Allergy and Infectious Diseases (NIAID)60 enrolled

Overview

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

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 * Evaluate the efficacy of AMG 714 followed by narrow band UVB (nbUVB) phototherapy

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Vitiligo

Interventions

AMG 714BIOLOGICAL

anti-IL-15 monoclonal antibody (Anti-IL-15 MAB)

PlaceboBIOLOGICAL

Placebo for AMG 714

nbUVB phototherapyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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 Protocol Section 3.4.2. 3. F-VASI ≥ 0.25 (Appendix 2 of Protocol). 4. T-VASI ≥ 3 (Appendix 2 of Protocol). 5. Willingness to: 1. Undergo nbUVB phototherapy, as outlined in Protocol Section 7.3. 2. Stop all other treatments for vitiligo from screening through the final follow up visit as outlined in Protocol Section 7.2. Exclusion Criteria: 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 10\^3/μL 2. Hemoglobin \< 10 g/dL 3. Platelets (Plt) \< 125,000/mm\^3 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 (Protocol 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 (Protocol 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.

Locations (7)

University of California, Irvine: Department of Dermatology

Irvine, California, United States

University of California Davis Health System: Department of Dermatology

Sacramento, California, United States

Yale University School of Medicine: Department of Dermatology

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24

An F-VASI35 responder is defined as a participant who has at least 35% improvement from Baseline in the facial vitiligo area scoring index (F-VASI). F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. Participants missing the F-VASI assessment at Week 24 are imputed as F-VASI35 non-responders.

Time frame: Week 24

Secondary Outcomes

Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Weeks 12, 36, 48.

Time frame: Weeks 12, 36, and 48

Proportion of Participants Achieving a ≥ 25% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI25) at Weeks 12, 24, 36, 48.

An F-VASI25 responder is defined as a participant who has at least 25% improvement from Baseline in the facial vitiligo area scoring index (F-VASI). F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. Participants missing the F-VASI assessment at any visit are imputed as F-VASI25 non-responders for that visit.

Data from ClinicalTrials.gov

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Tufts Medical Center: Department of Dermatology

Boston, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Northwell Health

Lake Success, New York, United States

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 50% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI50) at Weeks 12, 24, 36, 48

An F-VASI50 responder is defined as a participant who has at least 50% improvement from Baseline in the facial vitiligo area scoring index (F-VASI). F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. Participants missing the F-VASI assessment at any visit are imputed as F-VASI50 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 75% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI75) at Weeks 12, 24, 36, 48

An F-VASI75 responder is defined as a participant who has at least 75% improvement from Baseline in the facial vitiligo area scoring index (F-VASI). F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. Participants missing the F-VASI assessment at any visit are imputed as F-VASI75 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 90% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI90) at Weeks 12, 24, 36, 48

An F-VASI90 responder is defined as a participant who has at least 90% improvement from Baseline in the facial vitiligo area scoring index (F-VASI). F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. Participants missing the F-VASI assessment at any visit are imputed as F-VASI90 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 25% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI25) at Weeks 12, 24, 36, 48

A T-VASI25 responder is defined as a participant who has at least 25% improvement from Baseline in the total body vitiligo area scoring index (T-VASI). T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. Participants missing the T-VASI assessment at any visit are imputed as T-VASI25 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI35) at Weeks 12, 24, 36, 48

A T-VASI35 responder is defined as a participant who has at least 35% improvement from Baseline in the total body vitiligo area scoring index (T-VASI). T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. Participants missing the T-VASI assessment at any visit are imputed as T-VASI35 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 50% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI50) at Weeks 12, 24, 36, 48

A T-VASI50 responder is defined as a participant who has at least 50% improvement from Baseline in the total body vitiligo area scoring index (T-VASI). T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. Participants missing the T-VASI assessment at any visit are imputed as T-VASI50 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 75% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI75) at Weeks 12, 24, 36, 48

A T-VASI75 responder is defined as a participant who has at least 75% improvement from Baseline in the total body vitiligo area scoring index (T-VASI). T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. Participants missing the T-VASI assessment at any visit are imputed as T-VASI75 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Proportion of Participants Achieving a ≥ 90% Improvement From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI90) at Weeks 12, 24, 36, 48

A T-VASI90 responder is defined as a participant who has at least 90% improvement from Baseline in the total body vitiligo area scoring index (T-VASI). T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. Participants missing the T-VASI assessment at any visit are imputed as T-VASI90 non-responders for that visit.

Time frame: Weeks 12, 24, 36, and 48

Change From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at Weeks 12, 24, 36, 48

F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. A negative change from Baseline in the F-VASI signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Change From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI) at Weeks 12, 24, 36, 48

T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. A negative change from Baseline in the T-VASI signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Change From Baseline in the Vitiligo Extent Score (VES) at Weeks 12, 24, 36, 48

The Vitiligo Extent Score (VES) is a tool for measuring the total body surface area affected by vitiligo. Images are shown of varying extent of vitiligo lesions from least to greatest extent over different body locations. An image from each body location is selected by the investigator during the patient encounter that best reflects the extent to which vitiligo lesions are covering the body surface area (BSA). If lesions are covering an area larger than shown in the last photo, a \>75% but \<100% option can be selected. The online calculator at www.vitiligo-calculator.com will then use selected images to calculate the percentage of the body surface area involved or grade of extent per region (Grade 0 to 6). The VES has a possible range from 0 to 100, with higher scores indicating more severe disease. A negative change from Baseline in the VES signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Change From Baseline in the Vitiligo-specific Health-related Quality-of-life Instrument (VitiQoL) Score at Weeks 12, 24, 36, 48

The Vitiligo-specific Health-related Quality-of-life Instrument (VitiQoL) is a validated instrument that asks participants to rate various aspects of their vitiligo during the past month. The response to each question will be scored on a 0 (not at all) to 6 (all of the time) scale. The VitiQoL score is calculated as the sum of questions 1 through 15, providing a possible range from 0 to 90, with higher scores indicating more severe disease. A negative change from Baseline in the VitiQoL signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Proportion of Participants in Each Vitiligo Noticeability Scale (VNS) Category at Weeks 12, 24, 36, 48

The Vitiligo Noticeability Scale (VNS) is a validated patient-reported outcome measure of vitiligo treatment where participants will be presented with one pre-treatment photograph of their face and asked to answer the question: "Compared with before treatment, how noticeable is the vitiligo now?". The same pre-treatment photograph must be used at each visit. Scores range from 1 to 5 with a score of 1 being "More noticeable", 2 "As noticeable", 3 "Slightly less noticeable", 4 "A lot less noticeable", and 5 "No longer noticeable". Only participants with available data were analyzed.

Time frame: Weeks 12, 24, 36, and 48

Shifts From Baseline in the Distribution of Static Investigator Global Assessment (sIGA) Scores at Weeks 12, 24, 36, 48

The Static Investigator Global Assessment (sIGA) is a 5-point scale that grades the loss of pigmentation and severity of lesions on a participant's body. Lower scores represent lesser extent and lesser severity; higher scores represent greater extent and greater severity. A score of 0 represents clear skin, with no loss of pigmentation after a natural light or Woods lamp examination and a score of 4 represents severe vitiligo, with extensive loss of pigmentation affecting most areas of the body. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Percent Change From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at Weeks 12, 24, 36, 48

F-VASI assesses the area of the face affected by vitiligo. F-VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. F-VASI has a possible range from 0 to 3.5, with higher scores indicating more severe disease. A negative percent change from Baseline in the F-VASI signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Percent Change From Baseline in the Total Body Vitiligo Area Scoring Index (T-VASI) at Weeks 12, 24, 36, 48

T-VASI assesses the area of the body affected by vitiligo. The body is divided into 6 regions: head and neck, upper extremities, hands, torso, lower extremities, and feet. For each body region, the VASI is determined by the product of the percent of vitiligo involvement (percent of body surface area \[BSA\]) and the degree of depigmentation estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. The percentage of BSA (hand or thumb unit) vitiligo involvement was estimated to the nearest 0.1% by the Investigator. T-VASI is derived by summing the values of all body regions, providing a possible range from 0 to 99, with higher scores indicating more severe disease. A negative percent change from Baseline in the T-VASI signifies improvement. Only participants with available data were analyzed.

Time frame: Baseline; Weeks 12, 24, 36, and 48

Proportion of Participants With a Grade 2 or Higher Treatment-Emergent Adverse Event

A participant who experienced any Grade 2 or higher treatment-emergent adverse event. Includes all ≥ Grade 2 untoward or unfavorable medical occurrence(s) associated with investigational product administration or any study mandated procedures.

Time frame: Week 0 to Week 24, Week 0 to Week 48

Proportion of Participants With a Grade 3 or Higher Infectious Treatment-Emergent Adverse Event

A participant who experienced any Grade 3 or higher infectious treatment-emergent adverse event. Includes all ≥ Grade 3 infectious untoward or unfavorable medical occurrence(s).

Time frame: Week 0 to Week 24, Week 0 to Week 48