A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata (Up-AA)

AbbVie

Status and phase: Enrolling; Phase 3

Conditions: Alopecia Areata

Treatments: Drug: Upadacitinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06012240

M23-716

2023-505061-82-00 (Other Identifier)

Details and patient eligibility

About

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 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 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 or Study 2, 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 240 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.

Enrollment: 1,500 estimated patients

Sex: All

Ages: 12 to 63 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.
• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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1,500 participants in 17 patient groups

Study 1: Group 1 Upadacitinib Dose A

Experimental group

Description:

Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.

Treatment:

Drug: Upadacitinib

Study 1: Group 2 Upadacitinib Dose B

Experimental group

Description:

Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.

Treatment:

Drug: Upadacitinib

Study 1: Group 3 Placebo

Experimental group

Description:

Participants will receive matching placebo once daily for 24 weeks in Period A.

Treatment:

Drug: Placebo

Study 1: Group 4 Upadacitinib Dose A

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Study 1: Group 5 Upadacitinib Dose B

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Study 1: Group 6 Placebo

Experimental group

Description:

Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.

Treatment:

Drug: Placebo

Study 2: Group 1 Upadacitinib Dose A

Experimental group

Description:

Participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.

Treatment:

Drug: Upadacitinib

Study 2: Group 2 Upadacitinib Dose B

Experimental group

Description:

Participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.

Treatment:

Drug: Upadacitinib

Study 2: Group 3 Placebo

Experimental group

Description:

Participants will receive matching placebo once daily for 24 weeks in Period A.

Treatment:

Drug: Placebo

Study 2: Group 4 Upadacitinib Dose A

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Study 2: Group 5 Upadacitinib Dose B

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Study 2: Group 6 Placebo

Experimental group

Description:

Participants initially randomized to placebo with a SALT score ≤ 20 at Week 24 will continue on placebo through Week 160.

Treatment:

Drug: Placebo

Study 3: Group 1 Upadacitinib Dose B (SALT > 20)

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Study 3: Group 2 Upadacitinib Dose A (SALT ≤ 20)

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Study 3: Group 3 Upadacitinib Dose B (Non-Sustained)

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Study 3: Group 4 Upadacitinib Dose B (Sustained)

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Study 3: Group 5 Upadacitinib Dose A (Sustained)

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib