A Phase 3 Randomized, Placebo-controlled, Double-blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult and Adolescent Subjects With Severe Alopecia Areata
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,500
- 试验地点
- 548
- 主要终点
- Number of Participants with Adverse Events (AEs)
研究概览
简要总结
Alopecia areata (AA) is a disease that happens when the immune system attacks hair follicles and causes hair loss. AA usually affects the head and face, but hair loss can happen on any part of the body. The purpose of this study is to assess how safe, effective, and tolerable upadacitinib is in adolescent and adult participants with severe AA.
Upadacitinib is an approved drug being investigated for the treatment of AA. In Study 1 and Study 2 and Study 4 Period A, participants are placed in 1 of 3 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 5 chance that participants will be assigned to placebo. In Study 1 and Study 2 and Study 4 Period B, participants originally randomized to upadacitinib dose group in Period A will continue their same treatment in Period B. Participants originally randomized to Placebo in Period A will either remain on placebo in Period B, or be randomized in 1 of 2 groups, based off of their Severity of Alopecia Tool (SALT) score. Participants who complete Study 1, Study 2 or Study 4, can join Study 3 and may be re-randomized to receive 1 of 2 doses of upadacitinib for up to 108 weeks. Around 1500 participants with severe AA will be enrolled in the study at approximately 280 sites worldwide.
Participants will receive oral tablets of either upadacitinib or placebo once daily for up to 160 weeks with the potential of being re-randomized into a different treatment group at Weeks 24 and 52. Participants will be followed up for up to 30 days after last study drug dose.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 63 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult individuals must be < 64 years old at Baseline Visit. Where permitted outside United States (US)/European Union (EU), adolescent individuals who are at least 12 years old at Screening may participate in Study 1 and Study
- •Adolescent individuals in the US who are at least 12 years old at Screening may participate in Study
- •Diagnosis of severe alopecia areata (AA) with Severity of Alopecia Tool (SALT) score >= 50 scalp hair loss at Screening and Baseline.
- •Severe AA with no spontaneous scalp hair regrowth over the past 6 months.
- •Current episode of AA of less than 8 years.
排除标准
- •Current diagnosis of primarily diffuse type of AA.
- •Current diagnosis of other types of alopecia that would interfere with evaluation of AA, including but not limited to female pattern hair loss, male pattern hair loss (androgenetic alopecia) Stage III or greater based on Hamilton-Norwood classification, traction alopecia, lichen planopilaris (LPP), discoid lupus, frontal fibrosing alopecia (FFA), central centrifugal cicatricial alopecia (CCCA), folliculitis decalvans, trichotillomania, and telogen effluvium.
- •Diagnosis of other types of inflammatory scalp, eyebrow, or eyelash disorders that would interfere with evaluation of AA as determined by the investigator, including but not limited to seborrheic dermatitis, scalp psoriasis, atopic dermatitis (AD), and tinea capitis.
研究组 & 干预措施
Study 1: Group 2 Upadacitinib Dose B
Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 1: Group 4 Upadacitinib Dose A
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 2: Group 2 Upadacitinib Dose B
Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 3: Group 1 Upadacitinib Dose B (SALT > 20)
Participants receiving upadacitinib Dose A with a SALT score > 20 at Week 52 (end of Period B) of Study 1 or Study 2 will dose escalate to upadacitinib Dose B once daily for 108 weeks.
干预措施: Upadacitinib (Drug)
Study 2: Group 4 Upadacitinib Dose A
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 4: Group 2 Upadacitinib Dose B
US only adolescent participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 4: Group 5 Upadacitinib Dose B
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 4: Group 4 Upadacitinib Dose A
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 1: Group 5 Upadacitinib Dose B
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B.
干预措施: Placebo (Drug)
Study 1: Group 5 Upadacitinib Dose B
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 1: Group 3 Placebo
Participants will receive matching placebo once daily for 24 weeks in Period A.
干预措施: Placebo (Drug)
Study 1: Group 1 Upadacitinib Dose A
Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 3: Group 5 Upadacitinib Dose A (Sustained)
Participants who end Period B on upadacitinib Dose B with a with a SALT score ≤ 20 at Week 40 and Week 52 of Study 1 or Study 2 will be re-randomized to receive upadacitinib Dose A once daily for 108 weeks.
干预措施: Upadacitinib (Drug)
Study 1: Group 4 Upadacitinib Dose A
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B.
干预措施: Placebo (Drug)
Study 2: Group 3 Placebo
Participants will receive matching placebo once daily for 24 weeks in Period A.
干预措施: Placebo (Drug)
Study 2: Group 4 Upadacitinib Dose A
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose A once daily for 28 weeks in Period B.
干预措施: Placebo (Drug)
Study 1: Group 6 Placebo
Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
干预措施: Placebo (Drug)
Study 2: Group 5 Upadacitinib Dose B
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B.
干预措施: Upadacitinib (Drug)
Study 3: Group 4 Upadacitinib Dose B (Sustained)
Participants who end Period B on upadacitinib Dose B with a with a SALT score ≤ 20 at Week 40 and Week 52 of Study 1 or Study 2 will be re-randomized to receive upadacitinib Dose B once daily for 108 weeks.
干预措施: Upadacitinib (Drug)
Study 3: Group 2 Upadacitinib Dose A (SALT ≤ 20)
Participants receiving upadacitinib Dose A with a SALT score ≤ 20 at Week 52 (end of Period B) of Study 1 or Study 2 will remain on upadacitinib Dose A once daily for 108 weeks.
干预措施: Upadacitinib (Drug)
Study 2: Group 6 Placebo
Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
干预措施: Placebo (Drug)
Study 4: Group 3 Placebo
US only adolescent participants will receive matching placebo once daily for 24 weeks in Period A.
干预措施: Placebo (Drug)
Study 3: Group 3 Upadacitinib Dose B (Non-Sustained)
Participants who end Period B on upadacitinib Dose B with a with a SALT score > 20 at Week 40 or Week 52 of Study 1 or Study 2 will remain on upadacitinib Dose B once daily for 108 weeks.
干预措施: Upadacitinib (Drug)
Study 4: Group 1 Upadacitinib Dose A
US only adolescent participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 2: Group 1 Upadacitinib Dose A
Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.
干预措施: Upadacitinib (Drug)
Study 2: Group 5 Upadacitinib Dose B
Participants initially randomized to placebo (Period A) with a SALT score > 20 at Week 24 will be re-randomized to receive upadacitinib Dose B once daily for 28 weeks in Period B.
干预措施: Placebo (Drug)
Study 4: Group 6 Placebo
Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: Up to approximately 164 weeks
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Percentage of Participants with the Achievement of Severity of Alopecia Tool (SALT) Score <= 20
时间窗: Week 24
The SALT is a global AA severity score based on the combination of extent and density of scalp hair loss. The score is determined by visually defining the amount of terminal hair loss in each of the 4 views of the scalp (left and right side each accounting for 18% of scalp area, the top for 40%, and the back for 24%) and adding these together with a maximum score of 100%.
次要结局
- Achievement of SALT score <= 20 for the Comparison of Upadacitinib Dose A QD Versus Placebo(Week 24)
- Percentage of Participants with the Achievement of Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss of 0 or 1(Baseline to Week 24)
- Percent Change from Baseline in SALT Score(Baseline to Week 24)
- Percentage of Participants with the Achievement of Patient-Reported Outcome (PRO) for Scalp Hair Assessment 0/1 with ≥ 2-Point Improvement (Reduction)(Baseline to Week 24)
- Achievement of Hospital Anxiety and Depression Scale (HADS)-Anxiety < 8 and HADS-Depression < 8 at Week 24 Among Participants with HADS-A >= 8 or HADS-D >= 8 at Baseline(Baseline to Week 24)
- Percentage of Participants with the Achievement of SALT Score <= 10(Up to Week 24)
- Percentage of Participants with the Achievement of ClinRO Measure for Eyelash Hair Loss of 0 or 1(Baseline to Week 24)
- Percentage of Participants with the Achievement of SALT Score 0(Week 24)
- Percentage of Participants with the Achievement of SALT 90(Baseline to Week 24)
- Percentage of Participants with the Achievement of Patients' Global Impression of Change of Alopecia Areata (PaGIC-AA) Score of 1 "Much Better" or 2 "Moderately Better"(Up to Week 24)
- Change from Baseline in Alopecia Areata Symptom Impact Scale (AASIS) Interference Subscale Score(Week 24)
- Percentage of Participants with the Achievement of SALT Score <= 20(Up to Week 12)
- Change from Baseline in Skindex-16 AA Emotions Domain Scores(Week 24)
- Percentage of Participants with the Achievement of SALT 75(Baseline to Week 24)
- Change from Baseline in AASIS Symptoms Subscale Score(Week 24)
- Change from Baseline in Skindex-16 AA Functioning Domain Scores(Week 24)