Evaluation of AMG 714 for Vitiligo: A Phase 2a Randomized Double Blind Placebo Controlled Trial (ITN086AI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 14
- 主要终点
- Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24
研究概览
简要总结
This study is designed to evaluate the efficacy of AMG 714 for the treatment of adult participants with vitiligo.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Protocol Section 3.4.
- •F-VASI ≥ 0.25 (Appendix 2 of Protocol).
- •T-VASI ≥ 3 (Appendix 2 of Protocol).
- •Willingness to:
- •Undergo nbUVB phototherapy, as outlined in Protocol Section 7.
- •Stop all other treatments for vitiligo from screening through the final follow up visit as outlined in Protocol Section 7.2.
排除标准
- •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
- •Use of non-biologic systemic or topical immunosuppressive or immunomodulatory agents within 4 weeks prior to Visit
- •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
- •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
- •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 10^3/μL
- •Hemoglobin < 10 g/dL
- •Platelets (Plt) < 125,000/mm^3
- •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 (Protocol Section 7.4). Contraception or abstinence is required for 2 weeks prior to Visit
- •Women who are pregnant or lactating.
- •Vaccination with a live attenuated vaccine within 30 days prior to Visit
- •Known drug allergy or reaction to any component of AMG 714 (Protocol 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.
研究组 & 干预措施
AMG 714
Participants will be administered 300 mg AMG 714 beginning at Week 0 and every 2 weeks thereafter through Week 10 (for a total of 6 doses). Each dose will be administered as 2 subcutaneous injections (1.5 mL each).
干预措施: AMG 714 (Biological)
AMG 714
Participants will be administered 300 mg AMG 714 beginning at Week 0 and every 2 weeks thereafter through Week 10 (for a total of 6 doses). Each dose will be administered as 2 subcutaneous injections (1.5 mL each).
干预措施: nbUVB phototherapy (Procedure)
Placebo
Participants will be administered placebo as 2 subcutaneous injections (1.5 mL each) beginning at Week 0 and every 2 weeks thereafter through Week 10 (for a total of 6 doses).
干预措施: Placebo (Biological)
Placebo
Participants will be administered placebo as 2 subcutaneous injections (1.5 mL each) beginning at Week 0 and every 2 weeks thereafter through Week 10 (for a total of 6 doses).
干预措施: nbUVB phototherapy (Procedure)
结局指标
主要结局
Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24
时间窗: 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.
Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Week 24
时间窗: 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.
次要结局
- Proportion of Participants Achieving a ≥ 35% Improvement From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI35) at Weeks 12, 36, 48.(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.(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(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(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(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(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(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(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(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(Weeks 12, 24, 36, and 48)
- Change From Baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at Weeks 12, 24, 36, 48(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(Baseline; Weeks 12, 24, 36, and 48)
- Change From Baseline in the Vitiligo Extent Score (VES) at Weeks 12, 24, 36, 48(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(Baseline; Weeks 12, 24, 36, and 48)
- Proportion of Participants in Each Vitiligo Noticeability Scale (VNS) Category at Weeks 12, 24, 36, 48(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(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(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(Baseline; Weeks 12, 24, 36, and 48)
- Proportion of Participants With a Grade 2 or Higher Treatment-Emergent Adverse Event(Week 0 to Week 24, Week 0 to Week 48)
- Proportion of Participants With a Grade 3 or Higher Infectious Treatment-Emergent Adverse Event(Week 0 to Week 24, Week 0 to Week 48)