Clinical trial NCT04338581: Evaluation of AMG 714 for Vitiligo
Official title: Evaluation of AMG 714 for Vitiligo: A Phase 2a Randomized Double Blind Placebo Controlled Trial (ITN086AI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vitiligo
Keywords: efficacy
facial repigmentation
randomized placebo-controlled phase 2a trial
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
name: PPD Development, LP
name: Rho Federal Systems Division, Inc.
name: Amgen
First posted: 2020-04-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥35 (F-VASI35) at Week 12, Week 36, Week 48
timeFrame: Week 12, Week 36, Week 48
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥25 (F-VASI25) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥50 (F-VASI50) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥75 (F-VASI75) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving Face Vitiligo Area Scoring Index ≥90 (F-VASI90) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥25 (T-VASI25) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥35 (T-VASI35) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥50 (T-VASI50) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥75 (T-VASI75) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Proportion of Participants Achieving total body Vitiligo Area Scoring Index ≥90 (T-VASI90) at Week 12, Week 24, Week 36 and Week 48
timeFrame: Week 12, Week 24, Week 36, Week 48
measure: Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Change from Baseline (Day 0) in total body Vitiligo Area Scoring Index (T-VASI) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Change from Baseline (Day 0) in Vitiligo Extent Score (VES) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Change from Baseline (Day 0) in the Vitiligo Quality of Life (VitiQoL) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Change from Baseline (Day 0) in the Vitiligo Noticeability Scale (VNS) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Percentage Change from Baseline in Face Vitiligo Area Scoring Index (F-VASI) at Week 12, Week 24, Week 36, and Week 48
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: 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
timeFrame: Week 12, Week 24, Week 36, and Week 48
measure: Occurrence of ≥ Grade 2 Adverse Events (AEs)
timeFrame: Up to Week 48
measure: Occurrence of ≥ Grade 3 Infectious Adverse Events (AEs)
timeFrame: Up to Week 48
Other outcomes:
measure: EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve total body Vitiligo Area Scoring Index ≥35 (T-VAS135)
timeFrame: Up to 48 Weeks
measure: EXPLORATORY: Time-to-Event Analysis of Participants Who Achieve a F-VASI35
timeFrame: Up to 48 Weeks
measure: EXPLORATORY: AMG 714 Serum Levels
timeFrame: Week 6, Week 12
Locations:
city: Irvine
country: United States
facility: University of California, Irvine: Department of Dermatology
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System: Department of Dermatology
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine: Department of Dermatology
state: Connecticut
city: Boston
country: United States
facility: Tufts Medical Center: Department of Dermatology
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Philadelphia
country: United States
facility: Perelman School of Medicine, University of Pennsylvania: Department of Dermatology
state: Pennsylvania
Study officials:
affiliation: Yale University School of Medicine: Department of Dermatology
name: Brett A. King, MD, PhD
role: STUDY_CHAIR
References: