Vitiligo
Conditions
Keywords
efficacy, facial repigmentation, randomized placebo-controlled phase 2a trial
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 * Evaluate the efficacy of AMG 714 followed by narrow band UVB (nbUVB) phototherapy
Interventions
BIOLOGICALAMG 714
anti-IL-15 monoclonal antibody (Anti-IL-15 MAB)
BIOLOGICALPlacebo
Placebo for AMG 714
PROCEDUREnbUVB 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.
Sponsors
Immune Tolerance Network (ITN)
PPD Development, LP
Rho Federal Systems Division, Inc.
Amgen
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 AMG 714. Random assignment will be stratified by active versus stable vitiligo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24 | 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. |
Countries
United States
Participant flow
Recruitment details
Seven sites in the United States were activated. All seven sites randomized participants. The first site was activated in November 2020 and the last participant was randomized in May 2024.
Participants by arm
| Arm | Count |
|---|---|
| AMG 714 Participants receive 300 mg AMG 714 subcutaneously every 2 weeks for 6 doses beginning at Week 0 with the last dose at Week 10. | 40 |
| Placebo Participants receive placebo subcutaneously every 2 weeks for 6 doses beginning at Week 0 with the last dose at Week 10. | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Prohibited Medication | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Total | AMG 714 | Placebo |
|---|---|---|---|
| Age, Continuous | 50.7 Years STANDARD_DEVIATION 13.23 | 49.9 Years STANDARD_DEVIATION 12.75 | 52.4 Years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 35 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| F-VASI at Baseline | 1.116 Score on a Scale STANDARD_DEVIATION 0.9091 | 1.154 Score on a Scale STANDARD_DEVIATION 0.8982 | 1.035 Score on a Scale STANDARD_DEVIATION 0.9513 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 39 Participants | 27 Participants | 12 Participants |
| Region of Enrollment United States | 59 participants | 40 participants | 19 participants |
| Sex: Female, Male Female | 28 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 31 Participants | 21 Participants | 10 Participants |
| T-VASI at Baseline | 19.573 Score on a Scale STANDARD_DEVIATION 19.4434 | 19.901 Score on a Scale STANDARD_DEVIATION 21.4012 | 18.884 Score on a Scale STANDARD_DEVIATION 15.0015 |
| Vitiligo Type at Baseline Active Vitiligo | 34 Participants | 23 Participants | 11 Participants |
| Vitiligo Type at Baseline Stable Vitiligo | 25 Participants | 17 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 18 |
| other Total, other adverse events | 23 / 41 | 9 / 18 |
| serious Total, serious adverse events | 0 / 41 | 0 / 18 |
Outcome results
Primary
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
Population: The Modified Intent-to-Treat (mITT) population included all randomized participants who received at least one dose of either AMG 714 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 714 | Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24 | 0.150 Proportion of participants |
| Placebo | Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24 | 0.053 Proportion of participants |
Comparison: The p-value compares AMG 714 and Placebo treatment groups.p-value: 0.411Fisher Exact