Upadacitinib for Severe Alopecia Areata

(Up-AA Trial)

Recruiting at 267 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Diffuse AA, Other alopecia, Inflammatory disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 160 weeks

1500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether upadacitinib, a medication, is a safe and effective treatment for severe alopecia areata (AA), a condition where the immune system mistakenly attacks hair follicles, causing hair loss. Participants will receive either upadacitinib or a placebo (a "dummy" pill) to evaluate its effectiveness and potential side effects. The study seeks individuals with severe AA, significant scalp hair loss, and no hair regrowth in the past 6 months. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. Please consult with the trial coordinators for more information.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that upadacitinib is generally safe for people. In past studies, most participants tolerated it well, with serious side effects being rare. Specifically, only 1.4% to 2.8% of patients experienced serious side effects. Many others had mild side effects that did not require stopping treatment. The FDA has already approved upadacitinib for other uses, indicating that its safety profile is well understood. This knowledge helps doctors understand its effects on the body. While no treatment is completely risk-free, evidence suggests that upadacitinib is mostly well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about upadacitinib for severe alopecia areata because it offers a novel approach compared to current treatments like corticosteroids and immunosuppressants. Upadacitinib is a JAK inhibitor, which means it works by targeting the Janus kinase pathway involved in the inflammatory process that leads to hair loss. This mechanism is different from the traditional treatments that generally suppress the immune system more broadly. By focusing on a specific pathway, upadacitinib has the potential to be more effective with fewer side effects, making it a promising option for those with severe alopecia areata.

What evidence suggests that this trial's treatments could be effective for severe alopecia areata?

Research shows that upadacitinib may help treat alopecia areata (AA), a condition that causes hair loss. One study found that 35.2% of patients taking a 15 mg dose and 45.8% taking a 30 mg dose experienced significant hair regrowth, with 90% or more of their scalp covered with hair again. Many patients noticed hair regrowth within 1 to 4 months, particularly those with severe AA, such as alopecia universalis. This trial will evaluate different doses of upadacitinib, along with a placebo group, to determine its effectiveness for people with severe hair loss due to AA. ^{1 2 3 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults under 64 and adolescents at least 12 years old with severe alopecia areata (AA) can join this trial. They must have a SALT score ≥50 indicating significant scalp hair loss, no spontaneous hair regrowth in the past 6 months, and stable condition for the last 3 months. The current AA episode should be less than 8 years.

Inclusion Criteria

Do you have severe patchy hair loss from alopecia areata?

Have you been diagnosed with Alopecia Areata?

Exclusion Criteria

Have you been diagnosed with other types of hair loss (including male or female pattern baldness)?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral tablets of either upadacitinib or placebo once daily, with potential re-randomization at Weeks 24 and 52

160 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may join Study 3 and be re-randomized to receive upadacitinib for up to 108 weeks

108 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The study tests Upadacitinib's safety and effectiveness against severe AA compared to a placebo. Participants will take oral tablets daily for up to 160 weeks, with chances of being reassigned treatment based on their progress at specific intervals.

How Is the Trial Designed?

Group I: Study 4: Group 6 Placebo Experimental Treatment 1 Intervention

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

Group II: Study 4: Group 5 Upadacitinib Dose B Experimental Treatment 1 Intervention

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.

Group III: Study 4: Group 4 Upadacitinib Dose A Experimental Treatment 1 Intervention

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.

Group IV: Study 4: Group 3 Placebo Experimental Treatment 1 Intervention

US only adolescent participants will receive matching placebo once daily for 24 weeks in Period A.

Group V: Study 4: Group 2 Upadacitinib Dose B Experimental Treatment 1 Intervention

US only adolescent participants will receive upadacitinib Dose B once daily for 52 weeks in Period A and Period B.

Group VI: Study 4: Group 1 Upadacitinib Dose A Experimental Treatment 1 Intervention

US only adolescent participants will receive upadacitinib Dose A once daily for 52 weeks in Period A and Period B.

Group VII: Study 3: Group 5 Upadacitinib Dose A (Sustained) Experimental Treatment 1 Intervention

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.

Group VIII: Study 3: Group 4 Upadacitinib Dose B (Sustained) Experimental Treatment 1 Intervention

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.

Group IX: Study 3: Group 3 Upadacitinib Dose B (Non-Sustained) Experimental Treatment 1 Intervention

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.

Group X: Study 3: Group 2 Upadacitinib Dose A (SALT ≤ 20) Experimental Treatment 1 Intervention

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.

Group XI: Study 3: Group 1 Upadacitinib Dose B (SALT > 20) Experimental Treatment 1 Intervention

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.

Group XII: Study 2: Group 6 Placebo Experimental Treatment 1 Intervention

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

Group XIII: Study 2: Group 5 Upadacitinib Dose B Experimental Treatment 2 Interventions

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.

Group XIV: Study 2: Group 4 Upadacitinib Dose A Experimental Treatment 2 Interventions

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.

Group XV: Study 2: Group 3 Placebo Experimental Treatment 1 Intervention

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

Group XVI: Study 2: Group 2 Upadacitinib Dose B Experimental Treatment 1 Intervention

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

Group XVII: Study 2: Group 1 Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Group XVIII: Study 1: Group 6 Placebo Experimental Treatment 1 Intervention

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

Group XIX: Study 1: Group 5 Upadacitinib Dose B Experimental Treatment 2 Interventions

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.

Group XX: Study 1: Group 4 Upadacitinib Dose A Experimental Treatment 2 Interventions

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.

Group XXI: Study 1: Group 3 Placebo Experimental Treatment 1 Intervention

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

Group XXII: Study 1: Group 2 Upadacitinib Dose B Experimental Treatment 1 Intervention

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

Group XXIII: Study 1: Group 1 Upadacitinib Dose A Experimental Treatment 1 Intervention

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

Upadacitinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a study of 77 East Asian patients with advanced BRAF V600-mutant cutaneous melanoma, the combination of dabrafenib and trametinib showed a high objective response rate of 61%, indicating significant efficacy in treating this patient population.

The treatment was generally well-tolerated, with the most common adverse event being pyrexia (fever) occurring in 56% of patients, and serious adverse events were reported in 38%, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma. Si, L., Zhang, X., Shin, SJ., et al.[2020]

The THxID™-BRAF diagnostic test shows high accuracy in detecting BRAF V600E and V600K mutations in melanoma samples, with a positive agreement of 100% when compared to Sanger sequencing and a negative agreement of 100% with High Resolution Melting (HRM) testing.

This study indicates that the THxID™-BRAF test can be effectively used across various sample types, suggesting its potential for broader application beyond current guidelines, although further validation would be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the new FDA approved THxID™-BRAF test with High Resolution Melting and Sanger sequencing. Marchant, J., Mange, A., Larrieux, M., et al.[2021]

In the phase 2a ALLEGRO trial involving 142 adults with alopecia areata, both ritlecitinib and brepocitinib significantly improved patient-reported outcomes (AASIS scores) and clinician-assessed hair loss (SALT scores) after 24 weeks compared to placebo.

The study found medium-to-large correlations between patient-reported outcomes and clinician assessments, indicating that both measures are important for evaluating treatment effectiveness in alopecia areata.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the relationships between patient-reported outcomes and clinician assessments of alopecia areata in a phase 2a randomized trial of ritlecitinib and brepocitinib. Winnette, R., Banerjee, A., Sikirica, V., et al.[2022]

In a study involving 855 adults with severe alopecia areata, treatment with baricitinib (2 mg and 4 mg) showed continued improvement in scalp hair growth up to week 52, indicating its long-term efficacy.

Patients with a baseline Severity of Alopecia Tool (SALT) score of 50-94 responded better to baricitinib compared to those with scores of 95-100, and the higher 4 mg dose resulted in faster and greater response rates than the 2 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Baricitinib in Patients with Various Degrees of Alopecia Areata Severity: Post-Hoc Analysis from BRAVE AA1 and BRAVE AA2. Taylor, S., Korman, NJ., Tsai, TF., et al.[2023]

In a study involving 105 adolescents with alopecia areata, ritlecitinib showed significant efficacy, with 17%-28% achieving a SALT score of ≤20 (indicating minimal scalp hair loss) at 24 weeks, and 25%-50% at 48 weeks, compared to 0% in the placebo group.

Ritlecitinib was well-tolerated, with common side effects including headache and acne, but no serious adverse events like major cardiovascular issues or infections reported, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial. Hordinsky, M., Hebert, AA., Gooderham, M., et al.[2023]

Baricitinib, an oral JAK inhibitor, is the first approved treatment for adults with severe alopecia areata (AA) and has shown consistent benefits in hair regrowth compared to placebo in multiple randomized controlled trials.

The review highlighted that while baricitinib has robust evidence supporting its efficacy, many other treatments for moderate-to-severe AA lack thorough evaluation in clinical trials, leading to inconsistent data on their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for Moderate-to-Severe Alopecia Areata: A Systematic Narrative Review. Egeberg, A., Linsell, L., Johansson, E., et al.[2023]

In a study of 52 melanoma patients treated with the combination of dabrafenib and trametinib, 23% developed immune-related skin lesions (IRSLs), including panniculitis and vitiligo, which were linked to better treatment outcomes.

Patients with IRSLs had a significantly higher disease response rate (83% vs. 25%) and longer progression-free and overall survival, suggesting that these skin reactions could serve as predictive markers for positive treatment responses in advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy. Consoli, F., Manganoni, AM., Grisanti, S., et al.[2020]

Tofacitinib demonstrated a high effectiveness and acceptable safety profile in treating alopecia areata, with a complete response rate of 33.8% after 24 weeks in a cohort of 80 patients.

The study, which included 126 patients treated over a median duration of 23 weeks, showed a good drug retention rate, with 90% of patients remaining on the medication after 12 weeks, indicating its potential for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Survival and Long-term Outcome of Tofacitinib in Patients with Alopecia Areata: A Retrospective Study. Huang, J., Deng, S., Li, J., et al.[2023]

BRAF inhibitors, such as vemurafenib and dabrafenib, are effective treatments for stage IV metastatic melanoma with BRAF mutations, but they can cause rare side effects like panniculitis, which presents as tender, red nodules.

In a reported case, these nodules showed uptake on F-FDG PET/CT scans, potentially confusing them with signs of metastatic disease, highlighting the importance of recognizing this side effect during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF Inhibitor-Induced Panniculitis: Appearance on 18F-FDG PET/CT. Broski, SM., Moran, EK., Glazebrook, KN., et al.[2018]

In a study of 14 patients treated with dabrafenib and trametinib for an average of 24 weeks, all patients experienced at least one skin-related side effect, with papillomas being the most common.

The combination therapy can lead to serious skin issues, including the development of squamous cell carcinoma, highlighting the need for careful monitoring and management of these adverse effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Case Series of Cutaneous Adverse Effects Associated With Dabrafenib and Trametinib. Lacroix, JP., Wang, B.[2017]

Upadacitinib, a Janus kinase 1 inhibitor, successfully treated alopecia areata and atopic dermatitis in a pediatric patient after only 6 weeks of treatment.

The patient showed significant improvements in hair growth on both the scalp and body, indicating the potential efficacy of upadacitinib for these conditions, especially after minimal response to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib for the treatment of alopecia areata and severe atopic dermatitis in a paediatric patient: A case report. Bourkas, AN., Sibbald, C.[2022]

Citations

1. news.abbvie.com news.abbvie.com/2025-08-21-AbbVie-Announces-Positive-Topline-Results-from-Second-Phase-3-UP-AA-Trial-Evaluating-Upadacitinib-RINVOQ-R-for-Alopecia-Areata

AbbVie Announces Positive Topline Results from Second ... 35.2% and 45.8% of patients treated with upadacitinib 15 mg and 30 mg, respectively, reached 90% or more scalp hair coverage (SALT ≤ 10), ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06012240

NCT06012240 | A Study to Evaluate the Safety and ... The purpose of this study is to assess how safe, effective, and tolerable upadacitinib is in adolescent and adult participants with severe AA.

3. prnewswire.com prnewswire.com/news-releases/abbvie-announces-positive-topline-results-from-second-phase-3-up-aa-trial-evaluating-upadacitinib-rinvoq-for-alopecia-areata-302535765.html

AbbVie Announces Positive Topline Results from Second ... 35.2% and 45.8% of patients treated with upadacitinib 15 mg and 30 mg, respectively, reached 90% or more scalp hair coverage (SALT ≤ 10), ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40771447/

Upadacitinib for Alopecia: Current Evidence and Clinical ... Most experienced substantial or complete hair regrowth within 1–4 months, particularly those with severe forms like alopecia universalis or ophiasis.

5. clinicaltrials.icts.uci.edu clinicaltrials.icts.uci.edu/trial/NCT06012240

Upadacitinib Tablets in Adult and Adolescent Participants ... The purpose of this study is to assess how safe, effective, and tolerable upadacitinib is in adolescent and adult participants with severe AA.

6. news.abbvie.com news.abbvie.com/2024-04-25-New-Data-Show-RINVOQ-R-upadacitinib-Demonstrated-Superiority-Versus-DUPIXENT-R-dupilumab-Across-Primary-and-All-Secondary-Endpoints-in-an-Open-Label-Head-to-Head-Atopic-Dermatitis-Study

New Data Show RINVOQ® (upadacitinib) Demonstrated ... A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata (Up-AA) ...

7. dermnppa.org dermnppa.org/upadacitinib-shows-efficacy-for-alopecia-areata-in-phase-3-trials/

Upadacitinib Shows Efficacy for Alopecia Areata in Phase ... Treatment-emergent serious adverse events occurred in 1.4% and 2.8% of patients in the upadacitinib 15mg and 30mg groups, respectively, and none ...