A Study of Baricitinib (LY3009104) in Participants With Severe or Very Severe Alopecia Areata (BRAVE-AA1)

• ClinicalTrials.gov Identifier: NCT03570749
• Recruitment Status: Active, not recruiting
• First Posted: June 27, 2018
• Last Update Posted: February 3, 2022
• Sponsor: Eli Lilly and Company
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: June 18, 2018
• First Posted Date: June 27, 2018
• Last Update Posted Date: February 3, 2022
• Actual Study Start Date: September 24, 2018
• Actual Primary Completion Date: February 2, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2020)

Percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤ 20 [ Time Frame: Week 36 ]

Percentage of Participants Achieving SALT ≤ 20

Original Primary Outcome Measures (submitted: June 18, 2018)

Percentage of Participants Treated with the High Dose Baricitinib Achieving Alopecia Areata Investigator's Global Assessment (AA-IGA™) 0 or 1 with a ≥2 Point Improvement [ Time Frame: Week 36 ]

Percentage of participants treated with the high dose baricitinib achieving AA-IGA™ 0 or 1 with a ≥2 point improvement

Current Secondary Outcome Measures (submitted: January 15, 2021)

• Percentage of Participants Achieving 50% Improvement of SALT (SALT50) [ Time Frame: Week 12 ]
  Percentage of participants achieving SALT50
• 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 [ Time Frame: Week 36 ]
  Percentage of participants with 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
• Percent Change from Baseline in SALT Score [ Time Frame: Baseline, Week 36 ]
  Percent change from baseline in SALT score
• Time for Participants to Achieve SALT ≤ 20 [ Time Frame: Baseline through Week 36 ]
  Time for Participants to Achieve SALT ≤ 20
• 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) [ Time Frame: Week 36 ]
  Percentage of participants achieving ClinRO measure for EB hair loss 0 or 1 with ≥2-point improvement from Baseline (among participants with ClinRO measure for EB hair loss ≥2 at baseline)
• 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) [ Time Frame: Week 36 ]
  Percentage of participants achieving ClinRO measure for EL hair loss 0 or 1 with ≥2-point improvement from Baseline (among participants with ClinRO measure for EL hair loss ≥2 at baseline)
• 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) [ Time Frame: 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)
• 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) [ Time Frame: 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)
• Mean Change From Baseline in Hospital Anxiety Depression Scale (HADS) Anxiety Score [ Time Frame: Week 36 ]
  Mean Change From Baseline in HADS Anxiety Score
• Mean Change From Baseline in HADS Depression Score [ Time Frame: Week 36 ]
  Mean Change From Baseline in HADS Depression Score

Original Secondary Outcome Measures (submitted: June 18, 2018)

• Percentage of Participants Treated with the Low Dose Baricitinib Achieving AA-IGA™ 0 or 1 with a ≥2 Point Improvement [ Time Frame: Week 36 ]
  Percentage of participants treated with the low dose baricitinib achieving AA-IGA™ 0 or 1 with a ≥2 point improvement
• Mean Time for Participants to Achieve AA-IGA™ 0 or 1 with a ≥2 Point Improvement [ Time Frame: Baseline through Week 36 ]
  Mean time for participants to achieve AA-IGA™ 0 or 1 with a ≥2 point improvement
• Percentage of Participants Achieving 75% Improvement of Severity of Alopecia Tool (SALT75) [ Time Frame: Week 36 ]
  Percentage of participants achieving SALT75
• Percentage of Participants with Patient Reported Outcome (PRO) for Scalp Hair Assessment Score of 0 or 1 [ Time Frame: Week 36 ]
  Percentage of participants with PRO for scalp hair assessment score of 0 or 1
• Change from Baseline in SALT Score [ Time Frame: Baseline, Week 36 ]
  Change from baseline in SALT score
• Percentage of Participants Achieving Clinician Reported Outcome (ClinRO) Measure for EyeBrow (EB) Hair Loss 0 or 1 (Among Participants with ClinRO Measure for EB Hair Loss ≥2 at Baseline) [ Time Frame: Week 36 ]
  Percentage of participants achieving ClinRO measure for EB hair loss 0 or 1 (among participants with ClinRO measure for EB hair loss ≥2 at baseline)
• Percentage of Participants Achieving ClinRO Measure for Eye Lash (EL) Hair Loss 0 or 1 (Among Participants with ClinRO Measure for EL Hair Loss ≥2 at Baseline) [ Time Frame: Week 36 ]
  Percentage of participants achieving ClinRO measure for EL hair loss 0 or 1 (among participants with ClinRO measure for EL hair loss ≥2 at baseline)
• Percentage of Participants Achieving PRO Measure for EB 0 or 1 (Among Participants with PRO Measure for EB ≥2 at Baseline) [ Time Frame: Week 36 ]
  Percentage of participants achieving PRO measure for EB 0 or 1 (among participants with PRO measure for EB ≥2 at baseline)
• Percentage of Participants Achieving PRO Measure for EL 0 or 1 (Among Participants with PRO Measure EL ≥2 at Baseline) [ Time Frame: Week 36 ]
  Percentage of participants achieving PRO measure for EL 0 or 1 (among participants with PRO measure EL ≥2 at baseline)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Baricitinib (LY3009104) in Participants With Severe or Very Severe Alopecia Areata
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Alopecia Areata

Intervention

• Drug: Baricitinib
  Administered orally.
  Other Name: LY3009104
• Drug: Placebo
  Administered orally.

Study Arms

• Experimental: Baricitinib High Dose
  Baricitinib administered orally. Placebo administered orally to maintain the blind
  Interventions:

  • Drug: Baricitinib
  • Drug: Placebo
• Experimental: Baricitinib Low Dose
  Baricitinib administered orally. Placebo administered orally to maintain the blind.
  Interventions:

  • Drug: Baricitinib
  • Drug: Placebo
• Placebo Comparator: Placebo
  Placebo administered orally.
  Intervention: Drug: Placebo

• Publications *: King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, Hordinsky M, Dutronc Y, Wu WS, McCollam J, Chiasserini C, Yu G, Stanley S, Holzwarth K, DeLozier AM, Sinclair R; BRAVE-AA Investigators. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022 May 5;386(18):1687-1699. doi: 10.1056/NEJMoa2110343. Epub 2022 Mar 26.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 2, 2022): 764
• Original Estimated Enrollment (submitted: June 18, 2018): 725
• Estimated Study Completion Date: June 24, 2024
• Actual Primary Completion Date: February 2, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Are at least 18 years and ≤60 years for males (≤70 years of age for females) at the time of informed consent.

• 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 SALT (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. Note: participants who have severe or very severe AA for ≥8 years may be enrolled if episodes of regrowth, spontaneous or under treatment, have been observed on the affected areas over the past 8 years.
• Male or nonpregnant, nonbreastfeeding female participants.

Exclusion Criteria:

• 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, Korea, Republic of, Mexico, Puerto Rico, United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT03570749
• Other Study ID Numbers: 16582; I4V-MC-JAHO ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Incyte Corporation

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: February 2022