REVEAL: Evaluation of AMG 714 for Vitiligo
Study Details
Study Description
Brief Summary
This study is designed to evaluate the efficacy of AMG 714 for the treatment of adult participants with vitiligo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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-
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Assess the durability of the skin repigmentation achieved by AMG 714 in vitiligo, and
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Evaluate the efficacy of AMG 714 followed by narrow band UVB (nbUVB) phototherapy.
Study Design
Arms and Interventions
| 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). |
Biological: AMG 714
anti-IL-15 monoclonal antibody (Anti-IL-15 MAB)
Procedure: nbUVB phototherapy
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:
|
| 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). |
Biological: Placebo
Placebo for AMG 714
Procedure: nbUVB phototherapy
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:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 24 [Week 24]
≥35% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
Secondary Outcome Measures
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 12, Week 36, Week 48 [Week 12, Week 36, Week 48]
≥35% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥25 (F-VASI25) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥25% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥50 (F-VASI50) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥50% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥75 (F-VASI75) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥75% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
- Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥90 (F-VASI90) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥90% improvement from Baseline (Day 0) in Face Vitiligo Area Scoring Index (F-VASI) score.
- Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥25 (T-VASI25) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥ 25% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
- Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥35 (T-VASI35) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥ 35% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
- Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥50 (T-VASI50) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥ 50% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
- Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥75 (T-VASI75) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥ 75% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
- Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥90 (T-VASI90) at Week 12, Week 24, Week 36 and Week 48 [Week 12, Week 24, Week 36, Week 48]
≥ 90% improvement from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI)
- Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48 [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.
- Change from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI) at Week 12, Week 24, Week 36, and Week 48 [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.
- Change from Baseline (Day 0) in Vitiligo Extent Score (VES) at Week 12, Week 24, Week 36, and Week 48 [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.
- Change from Baseline (Day 0) in the Vitiligo Quality of Life (VitiQoL) at Week 12, Week 24, Week 36, and Week 48 [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.").
- Change from Baseline (Day 0) in the Vitiligo Noticeability Scale (VNS) at Week 12, Week 24, Week 36, and Week 48 [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.
- Percentage Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48 [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.
- 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 [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.
- Occurrence of ≥ Grade 2 Adverse Events (AEs) [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.
- Occurrence of ≥ Grade 3 Infectious Adverse Events (AEs) [Up to Week 48]
Includes all ≥ Grade 3 infectious untoward or unfavorable medical occurrence(s).
Other Outcome Measures
- EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve total body Vitiligo Area Scoring Index ≥35 (T-VAS135) [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.
- EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve a F-VASI35 [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.
- EXPLORATORY: AMG 714 Serum Levels [Week 6, Week 12]
Level of study product AMG 714 measured in the blood (serum) of participants.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must be able to understand and provide informed consent;
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A clinical diagnosis of active or stable vitiligo made by a dermatologist:
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Active vitiligo: New or expanding vitiligo lesions with or without the presence of confetti, trichrome, or inflammatory vitiligo lesion patterns or other clinical signs of active vitiligo in the past 3 months
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Stable vitiligo: No new depigmented lesions, and no confetti, trichrome, or inflammatory vitiligo lesion patterns or other clinical signs of active vitiligo in the past 3 months.
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Facial Vitiligo Area Scoring Index (F-VASI) ≥ 0.25;
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Total Body Vitiligo Area Scoring Index (T- VASI) ≥3; and
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Willingness to:
-
Undergo narrow band ultraviolet B (nbUVB) phototherapy
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Stop all other treatments for vitiligo from screening through the final follow up visit at week 48.
Exclusion Criteria:
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Inability or unwillingness of a participant to give written informed consent or comply with the study protocol;
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Diagnosis of segmental vitiligo;
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Contraindication to narrow band ultraviolet B (nbUVB) phototherapy;
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More than 33% leukotrichia on the face or on the total body;
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Use of biologic, investigational, or experimental therapy or procedure within 12 weeks or 5 half-lives prior to Visit 0 (whichever is longer);
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Use of laser or light-based treatment (phototherapy), including tanning beds within 8 weeks prior to Visit 0;
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Use of non-biologic systemic or topical immunosuppressive or immunomodulatory agents within 4 weeks prior to Visit 0;
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History of melanocyte-keratinocyte transplantation procedure (MKTP) or other surgical treatment for vitiligo;
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Current or past use of the depigmenting agent monobenzyl ether of hydroquinone, including Benoquin®(Monobenzone);
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Presence of skin conditions or lesions that would confound the vitiligo assessments;
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Spontaneous repigmentation within 6 months prior to Visit 0 (e.g., repigmentation without any treatment, and significant in amount as determined by the investigator);
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Uncontrolled thyroid function at screening as determined by the investigator:
--Note: 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;
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Greater than 3 adequately treated nonmetastatic basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) within 12 months prior to Visit 0, or a previous history of multiple BCC or SCC which may pose additional risks from participation in the study, in the opinion of the investigator;
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Previous or current diagnosis of other cancer, with the exception of adequately treated cervical carcinoma in situ;
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Acute or chronic infection, including:
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current use of suppressive therapy for chronic infection,
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hospitalization for treatment of infection within 90 days prior to Visit 0, or
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parenteral anti-microbial use within 90 days prior to Visit 0 (including anti-bacterial, anti-viral, or anti-fungal agents).
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Evidence of infection, including:
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Human immunodeficiency virus (HIV)
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Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb
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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), or
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Positive QuantiFERON-tuberculosis (TB) Gold or QuantiFERON-TB Gold Plus test ---Note: Purified protein derivative (PPD) skin test may be substituted for Quantiferon-TB Gold or Quantiferon-TB Gold Plus test.
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Any of the following laboratory abnormalities:
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White blood count (WBC) <3.5 x 10^3/µL
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Hemoglobin <10 g/dL
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Platelets (Plt) < 125,000/mm^3
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Alanine aminotransferase (ALT) ≥ Twice the Upper Limit of Normal (ULN)
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Aspartate aminotransferase (AST) ≥ Twice the Upper Limit of Normal (ULN).
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Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception until study Week 48.
--Note: Contraception is required for 2 weeks prior to Visit 0 through Week 48 of study participation.
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Women who are pregnant or lactating;
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Vaccination with a live attenuated vaccine within 30 days prior to Visit 0;
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Known drug allergy or reaction to any component of AMG 714 or proteins derived from mammalian cell lines;
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Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may:
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pose additional risks from participation in the study,
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may interfere with the participant's ability to comply with study requirements,
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or that may impact the quality or interpretation of the data obtained from the study, or
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Current, diagnosed mental illness (e.g. severe depression for example) 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, Irvine: Department of Dermatology | Irvine | California | United States | 92697 |
| 2 | University of California Davis Health System: Department of Dermatology | Sacramento | California | United States | 95816 |
| 3 | Yale University School of Medicine: Department of Dermatology | New Haven | Connecticut | United States | 06824 |
| 4 | Tufts Medical Center: Department of Dermatology | Boston | Massachusetts | United States | 02111 |
| 5 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
| 6 | Perelman School of Medicine, University of Pennsylvania: Department of Dermatology | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Immune Tolerance Network (ITN)
- PPD
- Rho Federal Systems Division, Inc.
- Amgen
Investigators
- Study Chair: Brett A. King, MD, PhD, Yale University School of Medicine: Department of Dermatology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Immune Tolerance Network (ITN)
- Division of Allergy, Immunology, and Transplantation (DAIT)
- National Institute of Allergy and Infectious Diseases (NIAID)
- NIH health information: Vitiligo
Publications
None provided.- DAIT ITN086AI
- NIAID CRMS ID#: 38677