Upadacitinib for Giant Cell Arteritis

(SELECT-GCA Trial)

Recruiting at 212 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Corticosteroids

Must not be taking: JAK inhibitors, IL-6 inhibitors

Disqualifiers: Infections, Pregnancy, Immunosuppressants, others

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

Compensation: Varies

Number of Visits: Unknown

438 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if upadacitinib, combined with reducing steroid doses, helps people with giant cell arteritis achieve and maintain remission by reducing inflammation. Upadacitinib has been approved for the treatment of rheumatoid arthritis, atopic dermatitis, and psoriatic arthritis, and is under investigation for other conditions.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as interleukin-6 inhibitors, methotrexate, and others listed in the exclusion criteria. You must also be on a stable dose of prednisone (or equivalent) at the start of the trial.

What data supports the effectiveness of the drug upadacitinib for treating giant cell arteritis?

Upadacitinib, a drug used for rheumatoid arthritis, has shown effectiveness in improving patient-reported outcomes and achieving remission in patients who did not respond well to other treatments. This suggests it may have potential benefits for other inflammatory conditions like giant cell arteritis. ^{1 2 3 4 5}

Is upadacitinib generally safe for humans?

Upadacitinib has been shown to have a good safety profile in clinical trials for various conditions, but it may increase the risk of shingles (herpes zoster) and should not be used with certain other medications. It is not recommended for people with active tuberculosis, serious infections, active cancer, or severe liver problems. ^{1 2 4 6 7}

What makes the drug Upadacitinib unique for treating Giant Cell Arteritis?

Upadacitinib is unique because it is a selective Janus kinase (JAK) inhibitor, which works by blocking specific enzymes involved in inflammation, and it has shown effectiveness in other inflammatory conditions like rheumatoid arthritis. This mechanism of action is different from traditional treatments like corticosteroids, which broadly suppress the immune system. ^{2 4 5 8 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for adults with Giant Cell Arteritis (GCA) who've been treated with high-dose steroids. They must have stable GCA suitable for a steroid tapering regimen and not have used JAK inhibitors or IL-6 inhibitors recently. Women must be non-reproductive or use birth control.

Inclusion Criteria

I have been diagnosed with giant cell arteritis.

I have been treated with high-dose steroids before and am currently on a daily dose.

My giant cell arteritis is stable enough to start reducing my steroid treatment.

Exclusion Criteria

I have previously taken a JAK inhibitor medication.

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have not taken IL-6 inhibitors in the last 4 weeks or had a disease flare on them.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive upadacitinib or placebo with a corticosteroid taper regimen for 52 weeks

52 weeks

Regular visits as per protocol

Treatment Period 2

Participants continue or withdraw upadacitinib to evaluate maintenance of remission

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Corticosteroid (CS)
• Placebo
• Upadacitinib

Trial Overview The study tests Upadacitinib's effectiveness and safety in GCA patients, comparing a combination of the drug with a 26-week steroid taper to placebo with a longer, 52-week taper. It also examines if continuing Upadacitinib maintains remission after initial success.

Participant Groups

Group I: 7.5 mg Upadacitinib + 26-week CS taper -> Placebo Experimental Treatment 1 Intervention

Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

Group II: 7.5 mg Upadacitinib + 26-week CS taper -> 7.5 mg Upadacitinib Experimental Treatment 1 Intervention

Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) in Period 2.

Group III: 7.5 mg Upadacitinib + 26-week CS taper Experimental Treatment 2 Interventions

Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.

Group IV: 15 mg Upadacitinib + 26-week CS taper -> Placebo Experimental Treatment 1 Intervention

Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

Group V: 15 mg Upadacitinib + 26-week CS taper -> 15 mg Upadacitinib Experimental Treatment 1 Intervention

Participants received 15 mg upadacitinib tablets administered orally once daily (QD) in Period 2.

Group VI: 15 mg Upadacitinib + 26-week CS taper Experimental Treatment 2 Interventions

Participants received 15 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.

Group VII: Placebo + 52-week CS taper Placebo Group 2 Interventions

Participants received placebo tablets for upadacitinib administered orally once daily (QD) for 52 weeks and a 52-week corticosteroid (CS) taper regimen during Period 1.

Group VIII: Placebo + 52-week CS taper -> Placebo Placebo Group 1 Intervention

Participants who achieved sustained remission for at least 24 weeks prior to the Week 52 visit (at the end of Period 1) OR at remission at the Week 52 visit only who were assigned to placebo tablets for upadacitinib administered orally once daily (QD) in Period 1 continued to receive placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

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

Findings from Research

In a study of 498 patients with rheumatoid arthritis who did not respond adequately to biologic treatments, both doses of upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes (PROs) such as pain, disability, and overall disease activity compared to placebo.

More patients taking upadacitinib reported clinically meaningful improvements in quality of life measures, with the number needed to treat (NNT) to achieve these improvements ranging from 4 to 7, indicating that upadacitinib is effective in enhancing the well-being of patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. Strand, V., Schiff, M., Tundia, N., et al.[2023]

In a 48-week study involving patients with rheumatoid arthritis who did not respond adequately to methotrexate, upadacitinib showed significant improvements in patient-reported outcomes compared to placebo and was at least as effective as adalimumab.

Patients treated with upadacitinib reported greater reductions in pain, disability, and stiffness, with more individuals achieving clinically meaningful improvements across various measures compared to those on adalimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Strand, V., Tundia, N., Bergman, M., et al.[2022]

In a study involving 596 patients from Central and Eastern Europe, upadacitinib 15 mg once daily showed significant efficacy in improving rheumatoid arthritis symptoms compared to placebo and adalimumab, with results maintained over 48 weeks.

While upadacitinib demonstrated clinical benefits, it also had a higher incidence of serious infections and herpes zoster compared to adalimumab, indicating a need for careful monitoring of safety in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients. Pavelka, K., Szekanecz, Z., Damjanov, N., et al.[2022]

In a study involving 661 patients with rheumatoid arthritis (RA) who did not respond adequately to conventional DMARDs, upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes such as pain, physical function, and overall disease activity after 12 weeks compared to placebo.

Patients taking upadacitinib reported clinically meaningful improvements in various measures, with the number needed to treat (NNT) for these benefits ranging from 4 to 8, indicating that a small number of patients need to be treated for one to experience significant improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. Strand, V., Pope, J., Tundia, N., et al.[2021]

In a 48-week study involving patients with rheumatoid arthritis, upadacitinib 15 mg daily was found to be more effective than adalimumab or placebo in improving disease symptoms and preventing joint damage when used alongside methotrexate.

Patients who switched from adalimumab to upadacitinib due to insufficient response showed a higher rate of achieving low disease activity compared to those switching from upadacitinib to adalimumab, indicating that upadacitinib may provide better outcomes for patients not responding to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Fleischmann, RM., Genovese, MC., Enejosa, JV., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Upadacitinib tartrate in rheumatoid arthritis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib: Mechanism of action, clinical and translational science. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Upadacitinib in patients from China, Brazil, and South Korea with rheumatoid arthritis and an inadequate response to conventional therapy. [2022]