Upadacitinib for Rheumatoid Arthritis

(SELECT-COMPARE Trial)

Not currently recruiting at 450 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Methotrexate

Must not be taking: JAK inhibitors

Disqualifiers: Adalimumab, Inadequate bDMARD response, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests upadacitinib, a medication for adults with moderately to severely active rheumatoid arthritis (RA), to evaluate its effectiveness and safety. Participants will receive different treatments, including upadacitinib, a placebo, or adalimumab (also known as Humira), to compare their effects on RA symptoms. Ideal participants have had RA for at least three months, are currently taking methotrexate, and continue to experience painful and swollen joints. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

You will need to stop taking all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) except for methotrexate (MTX). If you have been on a biological disease-modifying anti-rheumatic drug (bDMARD), a washout period (time without taking certain medications) is required.

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

Research has shown that upadacitinib, a treatment for rheumatoid arthritis, has been thoroughly studied for safety in humans. In past studies, most patients generally tolerated upadacitinib well. Some experienced side effects, but these were similar to those seen with other rheumatoid arthritis medications.

Studies have demonstrated that upadacitinib reduces rheumatoid arthritis symptoms while maintaining a consistent safety record, with side effects similar to those of other treatments. Additionally, the FDA has already approved upadacitinib for treating rheumatoid arthritis, providing reassurance about its safety.

However, discussing any concerns with a healthcare provider before joining a clinical trial is always important. They can provide more personalized information based on individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about upadacitinib for rheumatoid arthritis because it offers a unique approach compared to current treatments. While many standard therapies, like methotrexate or adalimumab, target broad immune responses, upadacitinib is a JAK inhibitor that more specifically targets pathways involved in the inflammatory process. This targeted action can potentially lead to better management of symptoms with fewer side effects. Also, upadacitinib is administered orally, which can be more convenient than some injectable treatments, making it a promising option for patients seeking effective and easier-to-manage treatment plans.

What evidence suggests that this trial's treatments could be effective for rheumatoid arthritis?

Research has shown that upadacitinib, one of the treatments in this trial, effectively treats rheumatoid arthritis (RA). One study found that patients taking upadacitinib experienced significant symptom improvement, with more achieving at least a 20% reduction in joint symptoms compared to those on a placebo. Long-term evidence indicates that upadacitinib remains effective for up to five years. It acts as a JAK-1 inhibitor, reducing inflammation and preventing joint damage in RA patients. Overall, the research supports upadacitinib as a promising treatment option for those with moderately to severely active RA. ^{2 6 7 8 9}

Who Is on the Research Team?

AbbVie Inc.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with moderately to severely active rheumatoid arthritis who have been on a stable dose of methotrexate but haven't responded well to it. Participants must have at least 6 swollen and tender joints, evidence of bone erosion or positive RA markers, and may have had limited exposure to one other RA drug (not adalimumab). Those with other joint diseases or previous JAK inhibitor use are excluded.

Inclusion Criteria

I have 6 or more swollen and tender joints.

I have stopped taking all rheumatic disease drugs except for methotrexate.

I have tried only one bDMARD (not adalimumab) for my condition and either couldn't tolerate it or used it for less than 3 months.

Exclusion Criteria

I have previously taken JAK inhibitor medications.

I have tried adalimumab or similar medications without enough improvement.

I have a history of joint disease, but not RA. Secondary Sjogren's Syndrome is okay.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized treatment with upadacitinib, placebo, or adalimumab for up to 48 weeks, with potential switches based on response criteria

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term extension

Participants continue study treatment as assigned at the end of Period 1 for up to 5 years, with ongoing assessment of joint improvement

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab
• Placebo for Adalimumab
• Placebo for Upadacitinib
• Upadacitinib

Trial Overview The trial is testing the effectiveness and safety of Upadacitinib compared to a placebo and Adalimumab in adults with rheumatoid arthritis. All participants are already taking Methotrexate. The goal is to see if Upadacitinib can better reduce joint inflammation and prevent further damage.

How Is the Trial Designed?

Group I: Upadacitinib Experimental Treatment 3 Interventions

Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

Group II: Adalimumab Active Control 3 Interventions

Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index \[CDAI\] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

Group III: Placebo followed by ABT-494 Placebo Group 3 Interventions

Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1). Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.

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 involving 3209 patients, upadacitinib (15 mg daily) showed a comparable risk of major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer), and venous thromboembolism (VTE) when compared to adalimumab in patients with rheumatoid arthritis at higher cardiovascular risk.

However, upadacitinib was associated with higher rates of serious infections, herpes zoster, and non-melanoma skin cancer compared to the other treatments, indicating a need for careful monitoring in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. Fleischmann, R., Curtis, JR., Charles-Schoeman, C., 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]

Upadacitinib, an oral JAK-1 inhibitor, received marketing approval in the USA in August 2019 for treating moderately to severely active rheumatoid arthritis after showing positive results in multinational phase III trials.

The approval was specifically for patients who had an inadequate response or intolerance to methotrexate, highlighting its role as an effective alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib: First Approval. Duggan, S., Keam, SJ.[2020]

Upadacitinib, a once-daily oral JAK inhibitor, showed significant efficacy in achieving remission and low disease activity in approximately 4400 rheumatoid arthritis patients across five pivotal trials, outperforming placebo and other treatments like methotrexate and adalimumab.

While upadacitinib was associated with an increased risk of herpes zoster and creatine phosphokinase elevations, its overall safety profile was comparable to that of methotrexate and adalimumab, suggesting a favorable benefit-risk balance for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in Rheumatoid Arthritis: A Benefit-Risk Assessment Across a Phase III Program. Conaghan, PG., Mysler, E., Tanaka, Y., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5132065/

Efficacy and Safety of ABT‐494, a Selective JAK‐1 Inhibitor, in ... At week 12, the proportion of ACR20 responses was higher with ABT‐494 (62%, 68%, 80%, 64%, and 76% for the 3, 6, 12, 18, and 24 mg doses, respectively) than ...

2. rinvoqhcp.com rinvoqhcp.com/rheumatoid-arthritis/efficacy

RINVOQ® (upadacitinib) Efficacy for Rheumatoid Arthritis View clinical trial overview and efficacy data that studied the effects of RINVOQ on moderate to severe Rheumatoid Arthritis.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02706847

NCT02706847 | A Study to Compare Upadacitinib (ABT- ... A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying ...

4. news.abbvie.com news.abbvie.com/2023-05-24-AbbVie-Presents-Long-Term-Data-Further-Supporting-the-Efficacy-and-Safety-Profile-of-RINVOQ-R-upadacitinib-Across-Multiple-Rheumatic-Diseases-at-the-EULAR-2023-Congress

AbbVie Presents Long-Term Data Further Supporting the ... Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease ...

5. rmdopen.bmj.com rmdopen.bmj.com/content/10/2/e004007

Long-term safety and efficacy of upadacitinib versus ... These results support a favourable benefit–risk profile for upadacitinib in the long-term treatment of RA, up to at least 5 years. Introduction.

6. rinvoqhcp.com rinvoqhcp.com/dermatology/safety

RINVOQ® (upadacitinib) Safety Data IMPORTANT SAFETY INFORMATION & INDICATIONS1. INDICATIONS1. RINVOQ tablets are indicated for the treatment of: Moderately to severely active rheumatoid arthritis ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02706847

NCT02706847 | A Study to Compare Upadacitinib (ABT- ... The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo.

8. jrheum.org jrheum.org/content/51/7/663

Upadacitinib in Rheumatoid Arthritis and Inadequate ... To report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000349672432271X

SAT0236 Long-term safety and efficacy of upadacitinib ... The safety profile of UPA remained consistent with that expected for an RA population treated with JAKi. Efficacy responses were maintained up to 72 wks in pts ...