A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Operationally Seamless, Adaptive Phase 2/3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Severe or Very Severe Alopecia Areata
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 784
- 试验地点
- 148
- 主要终点
- Percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤ 20 - Phase 3
研究概览
简要总结
This study is designed to select up to two doses of baricitinib (referred to as low dose and high dose) and assess their efficacy and safety for the treatment of severe or very severe alopecia areata. An additional subpopulation of 60 participants in the US will enroll in the open-label addenda.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are at least 18 years and ≤60 years for males (≤70 years of age for females) at the time of informed consent.
- •Must self-identify as either Black or African American in race in the open label addenda.
- •Have severe or very severe AA, as determined by all of the following:
- •Current AA episode of more than 6 months' duration and hair loss encompassing ≥50% of the scalp, as measured by -- Severity of Alopecia Tool (SALT) Alopecia Areata (AA) Investigator Global Assessment (AA-IGA) of 3 or 4) at screening and baseline.
- •No spontaneous improvement over the past 6 months.
- •Current episode of severe or very severe AA of less than 8 years.
- •Male or nonpregnant, nonbreastfeeding female participants.
排除标准
- •Primarily "diffuse" type of AA.
- •Are currently experiencing other forms of alopecia or any other concomitant conditions that would interfere with evaluations of the effect of study medication on AA.
- •Previously treated with an oral Janus kinase (JAK) inhibitor and had an inadequate response (for example, absence of significant terminal hair growth after at least 12 weeks of treatment).
研究组 & 干预措施
Placebo Phase 3
Participants received two placebo tablets administered orally QD. Rescue therapy with Baricitinib 2 mg or 4 mg was provided to participants who failed to achieve SALT≤20 during this treatment period.
干预措施: Placebo (Drug)
2 mg Baricitinib Phase 3
Participants received one 2 mg Baricitinib tablet administered orally QD, and one placebo tablet administered orally QD to maintain the blind.
干预措施: Baricitinib (Drug)
Placebo Phase 2
Participants received three placebo tablets administered orally once daily (QD). Rescue therapy with Baricitinib 2 mg or 4 mg was provided to participants who failed to achieve Severity of Alopecia Tool (SALT) ≤20 (less than or equal to 20) during the study period.
干预措施: Placebo (Drug)
Placebo/ Placebo Phase 3
Participants who received two placebo tablets administered orally QD in Period 1 continue to receive the same placebo in Period 2.
干预措施: Placebo (Drug)
2 mg Baricitinib / Placebo Phase 3
Participants who received 2 mg Baricitinib at Period 1 switched to receive Placebo administered orally QD in Period 2.
干预措施: Placebo (Drug)
4 mg Baricitinib / Placebo Phase 3
Participants who received 4 mg Baricitinib at Period 1 switched to receive Placebo administered orally QD in Period 2.
干预措施: Placebo (Drug)
2 mg Baricitinib Phase 2
Participants received one 2 mg Baricitinib tablet administered orally QD, and two placebo tablets administered orally QD to maintain the blind.
干预措施: Baricitinib (Drug)
1 Milligram (mg) / 4 mg Baricitinib Phase 2
Participants received one 1 mg baricitinib tablet administered orally QD and two placebo tablets administered orally QD to maintain the blind through Week 12. Following the decision point at Week 12, participants were transitioned to receive one 4 mg baricitinib tablet administered orally QD and two placebo tablets administered orally QD to maintain the blind, and continued treatment through Week 200.
干预措施: Baricitinib (Drug)
Placebo Phase 3
Participants received two placebo tablets administered orally QD. Rescue therapy with Baricitinib 2 mg or 4 mg was provided to participants who failed to achieve SALT≤20 during this treatment period.
干预措施: Baricitinib (Drug)
4 mg Baricitinib Phase 2
Participants received one 4 mg Baricitinib tablet administered orally, QD and two placebo tablets QD administered orally to maintain the blind.
干预措施: Baricitinib (Drug)
Placebo Phase 2
Participants received three placebo tablets administered orally once daily (QD). Rescue therapy with Baricitinib 2 mg or 4 mg was provided to participants who failed to achieve Severity of Alopecia Tool (SALT) ≤20 (less than or equal to 20) during the study period.
干预措施: Baricitinib (Drug)
4 mg Baricitinib Phase 3
Participants received one 4 mg Baricitinib tablet administered orally QD, and one placebo tablet administered orally QD to maintain the blind.
干预措施: Baricitinib (Drug)
4 mg Baricitinib /4 mg Baricitinib Phase 3
Participants who received 4 mg Baricitinib at Period 1 continued to receive 4 mg Baricitinib administered orally QD in Period 2.
干预措施: Baricitinib (Drug)
2 mg Baricitinib /4 mg Baricitinib Phase 3
Participants who received 2 mg Baricitinib at Period 1 switched to receive 4 mg Baricitinib dose administered orally QD in Period 2.
干预措施: Baricitinib (Drug)
Placebo/ 2 mg Baricitinib Phase 3
Participants who received Placebo at Period 1 switched to receive 2 mg Baricitinib dose administered orally QD in Period 2.
干预措施: Baricitinib (Drug)
2 mg Baricitinib /2 mg Baricitinib Phase 3
Participants who received 2 mg Baricitinib at Period 1 continued to receive 2 mg Baricitinib dose administered orally QD in Period 2.
干预措施: Baricitinib (Drug)
4 mg Baricitinib Phase 3 Open-Label Addendum
Participants who received one 4 mg Baricitinib tablet administered orally QD.
干预措施: Baricitinib (Drug)
Placebo/ 4 mg Baricitinib Phase 3
Participants who received Placebo at Period 1 switched to receive 4 mg Baricitinib dose administered orally QD in Period 2.
干预措施: Baricitinib (Drug)
结局指标
主要结局
Percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤ 20 - Phase 3
时间窗: Week 36
The SALT uses a visual aid showing the division of the scalp hair into 4 areas with the top of the head constituting 40% of total surface, the posterior/back of head 24%, right side and left side of head 18% each. The percentage of hair loss in each area is determined and is multiplied by the percentage of scalp covered by that area. The total sum of the 4 products of each area will give the SALT score, as developed by the National Alopecia Areata Foundation Working Committee. Only terminal hair is included in the SALT; vellus hair or any fine downy hair is not taken into account in the SALT scoring process. The SALT score will range from 0% to 100%, with lower score indicating better health outcomes.
Percent Change From Baseline in SALT Score - Phase 3 Open-Label Addendum
时间窗: Baseline, Week 52
The SALT uses a visual aid showing the division of the scalp hair into 4 areas with the top of the head constituting 40% of total surface, the posterior/back of head 24%, right side and left side of head 18% each. The percentage of hair loss in each area is determined and is multiplied by the percentage of scalp covered by that area. The total sum of the 4 products of each area will give the SALT score, as developed by the National Alopecia Areata Foundation Working Committee. Only terminal hair is included in the SALT; vellus hair or any fine downy hair is not taken into account in the SALT scoring process. The SALT score will range from 0% to 100, with lower score indicating better health outcomes.
Percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤ 20 - Phase 3
时间窗: Week 36
The SALT uses a visual aid showing the division of the scalp hair into 4 areas with the top of the head constituting 40% of total surface, the posterior/back of head 24%, right side and left side of head 18% each. The percentage of hair loss in each area is determined and is multiplied by the percentage of scalp covered by that area. The total sum of the 4 products of each area will give the SALT score, as developed by the National Alopecia Areata Foundation Working Committee. Only terminal hair is included in the SALT; vellus hair or any fine downy hair is not taken into account in the SALT scoring process. The SALT score will range from 0% to 100%, with lower score indicating better health outcomes.
次要结局
- Percentage of Participants With Patient Reported Outcome (PRO) for Scalp Hair Assessment Score of 0 or 1 With a ≥ 2 Point Improvement From Baseline Among Participants With a Score of ≥ 3 at Baseline - Phase 3(Week 36)
- Percentage of Participants Achieving PRO Measure for EB 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With PRO Measure for EB ≥ 2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving PRO Measure for EL 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With PRO Measure EL ≥2 at Baseline) - Phase 3(Week 36)
- Percent Change From Baseline in SALT Score - Phase 3(Baseline, Week 36)
- Percentage of Participants Achieving 50% Improvement of SALT (SALT50) - Phase 3(Week 12)
- Mean Change From Baseline in Hospital Anxiety Depression Scale (HADS) Anxiety Score - Phase 3(Baseline, Week 36)
- Mean Change From Baseline in HADS Depression Score - Phase 3(Baseline, Week 36)
- Time for Participants to Achieve SALT ≤ 20 at Week 36 - Phase 3(Week 36)
- Percentage of Participants Achieving Clinician Reported Outcome (ClinRO) Measure for Eyebrow (EB) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EB Hair Loss ≥ 2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving ClinRO Measure for Eyelash (EL) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EL Hair Loss ≥ 2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving SALT ≤ 20 - Phase 3 Open-Label Addendum(Week 52)
- Percentage of Participants Achieving 50% Improvement of SALT (SALT50) - Phase 3 Open-Label Addendum(Week 52)
- Percentage of Participants Achieving ClinRO Measure for Eyebrow (EB) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EB Hair Loss ≥ 2 at Baseline) - Phase 3 Open-Label Addendum(Week 52)
- Percentage of Participants Achieving ClinRO Measure for Eyelash (EL) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EL Hair Loss ≥ 2 at Baseline) - Phase 3 Open-Label Addendum(Week 52)
- Percentage of Participants With Patient Reported Outcome (PRO) for Scalp Hair Assessment Score of 0 or 1 With a ≥ 2 Point Improvement From Baseline Among Participants With a Score of ≥ 3 at Baseline - Phase 3 Open-Label Addendum(Week 52)
- Percentage of Participants With Patient Reported Outcome (PRO) for Scalp Hair Assessment Score of 0 or 1 With a ≥ 2 Point Improvement From Baseline Among Participants With a Score of ≥ 3 at Baseline - Phase 3(Week 36)
- Percentage of Participants Achieving PRO Measure for EB 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With PRO Measure for EB ≥ 2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving PRO Measure for EL 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With PRO Measure EL ≥2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving Clinician Reported Outcome (ClinRO) Measure for EyeBrow (EB) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EB Hair Loss ≥ 2 at Baseline) - Phase 3(Week 36)
- Percentage of Participants Achieving ClinRO Measure for Eye Lash (EL) Hair Loss 0 or 1 With ≥ 2-point Improvement From Baseline (Among Participants With ClinRO Measure for EL Hair Loss ≥ 2 at Baseline) - Phase 3(Week 36)
- Percent Change From Baseline in SALT Score - Phase 3(Baseline, Week 36)
- Percentage of Participants Achieving 50% Improvement of SALT (SALT50) - Phase 3(Week 12)
- Time for Participants to Achieve SALT ≤ 20(Week 52)
- Mean Change From Baseline in Hospital Anxiety Depression Scale (HADS) Anxiety Score - Phase 3(Baseline, Week 36)
- Mean Change From Baseline in HADS Depression Score - Phase 3(Baseline, Week 36)