Upadacitinib for Axial Spondyloarthritis

(SELECT-AXIS 2 Trial)

No longer recruiting at 298 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: JAK inhibitors

Disqualifiers: Total spinal ankylosis, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called upadacitinib, a Janus kinase inhibitor, to determine its effectiveness in reducing symptoms of axial spondyloarthritis (axSpA), a type of arthritis affecting the spine. Researchers are studying two groups: one with ankylosing spondylitis and another with non-radiographic axial spondyloarthritis. The trial compares upadacitinib to a placebo to assess its impact on pain and inflammation and to evaluate its safety for long-term use. Suitable participants have active axSpA, have not responded well to treatments like bDMARDs, and experience significant back pain. 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 option.

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

The trial requires that any previous biologic disease-modifying antirheumatic drugs (bDMARDs) must be stopped before participating. However, the protocol does not specify if you need to stop other medications, so it's best to discuss this with the trial team.

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

Research has shown that upadacitinib is generally safe for individuals with conditions like ankylosing spondylitis. Studies have found that patients switching from a placebo to upadacitinib experience similar benefits to those who start on the drug immediately. In terms of safety, researchers have reported no major concerns. One study found that upadacitinib helped many patients reduce their symptoms compared to those taking a placebo. This suggests that the drug is not only effective but also safe enough for consideration in these trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for axial spondyloarthritis?

Upadacitinib is unique because it targets and inhibits Janus kinase (JAK), which plays a crucial role in the inflammatory processes of axial spondyloarthritis. Unlike traditional treatments like NSAIDs and biologic DMARDs that primarily focus on symptom relief or blocking specific inflammatory pathways, upadacitinib offers a more targeted approach by interfering directly with the JAK pathway. This mechanism of action is promising because it has the potential to reduce inflammation more effectively and improve patient outcomes in a condition that can be challenging to manage with existing treatments.

What evidence suggests that upadacitinib could be an effective treatment for axial spondyloarthritis?

Research has shown that upadacitinib, which participants in this trial may receive, can effectively reduce symptoms of axial spondyloarthritis (axSpA). One study found that patients with ankylosing spondylitis (a type of axSpA) reported a 39% improvement in back pain after 14 weeks, compared to a 19% improvement in those who took a placebo. Another study demonstrated that the benefits of upadacitinib lasted for two years, with many patients experiencing significant improvement. Additionally, patients who switched from a placebo to upadacitinib in this trial also showed meaningful relief from symptoms over time. Overall, these results suggest that upadacitinib may be a promising treatment for people with active axSpA. ^{3 5 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with active axial spondyloarthritis, including those who didn't respond well to certain rheumatic disease treatments (bDMARDs), can join this trial. Participants must have a specific level of disease activity and back pain, and not be fully fused in the spine due to ankylosis. They shouldn't have used JAK inhibitors before or be allergic to study drug ingredients.

Inclusion Criteria

You are allowed to participate in the study if you have received bDMARD therapy before.

My arthritis did not improve with biologic medication.

Study 1: You have been diagnosed with ankylosing spondylitis (AS) and meet specific criteria called the modified New York Criteria for AS. OR Study 2: You have been diagnosed with non-radiographic axial spondyloarthritis (nr-axSpA) and meet specific criteria called the ASAS classification criteria for axSpA. You also have active inflammation shown on MRI or have high sensitivity C-reactive protein (CRP) levels.

Exclusion Criteria

I have stopped taking any biologic DMARDs as required.

I have never taken any JAK inhibitor medications.

You cannot have had an allergic reaction or severe sensitivity to the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Period

Participants are randomized to receive either upadacitinib or placebo

14 weeks for Study 1, 52 weeks for Study 2

Open-Label Extension Period

Participants receive open-label upadacitinib after the double-blind period

90 weeks for Study 1, 52 weeks for Study 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Remission-Withdrawal Period

Participants in remission at Week 104 have the option to enroll in a remission-withdrawal period

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Upadacitinib

Trial Overview The trial is testing Upadacitinib's effectiveness compared to a placebo in reducing symptoms for two groups: one with ankylosing spondylitis (AS) that didn’t respond well to bDMARDs, and another with non-radiographic axial spondyloarthritis (nr-axSpA). It also looks at how safe and tolerable the drug is over time.

How Is the Trial Designed?

Group I: Study 2: Upadacitinib 15 mg Experimental Treatment 1 Intervention

Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).

Group II: Study 1: Upadacitinib 15 mg Experimental Treatment 1 Intervention

Participants receive 15 mg upadacitinib orally once a day for 104 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).

Group III: Study 1: Placebo Placebo Group 2 Interventions

Participants receive matching placebo for 14 weeks and then switch to receive 15 mg upadacitinib orally once a day for 90 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).

Group IV: Study 2: Placebo Placebo Group 2 Interventions

Participants receive matching placebo for 52 weeks and then switch to receive 15 mg upadacitinib orally once a day for 52 weeks. Participants who flare after 104 weeks will receive open-label upadacitinib once daily from the time of flare for 24 weeks (re-treatment).

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04169373

NCT04169373 | A Study to Evaluate Efficacy and Safety of ... To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adults with active axial spondyloarthritis (axSpA) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9299108/

Safety and Efficacy of Upadacitinib in Patients With Active ... Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed ...

3. news.abbvie.com news.abbvie.com/2021-10-07-AbbVies-Upadacitinib-RINVOQ-R-Met-Primary-and-Most-Ranked-Secondary-Endpoints-in-Phase-3-Study-for-Non-Radiographic-Axial-Spondyloarthritis

AbbVie's Upadacitinib (RINVOQ®) Met Primary and Most ... Additionally, patients treated with upadacitinib experienced significantly greater improvement in physical function as assessed by mean change ...

4. rinvoqhcp.com rinvoqhcp.com/ankylosing-spondylitis/efficacy

RINVOQ® (upadacitinib) Efficacy for Ankylosing Spondylitis Improvement in Total Back Pain and Nocturnal Back Pain · 39% improvement (n=206) vs 19% (n=203) with placebo at Week 14 as observed and 68% improvement (n=168) ...

5. rmdopen.bmj.com rmdopen.bmj.com/content/8/2/e002280

Upadacitinib in active ankylosing spondylitis - RMD Open Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints.

6. news.abbvie.com news.abbvie.com/2021-10-07-AbbVies-RINVOQ-R-upadacitinib-Met-Primary-and-All-Ranked-Secondary-Endpoints-in-Phase-3-Study-in-Ankylosing-Spondylitis

AbbVie's RINVOQ® (upadacitinib) Met Primary and All ... RINVOQ (upadacitinib) met the primary endpoint of ASAS40 at week 14 versus placebo (45 percent compared to 18 percent) in patients with ankylosing spondylitis.

7. qrheumatol.com qrheumatol.com/articles/upadacitinib-in-action-efficacy-and-safety-in-the-treatment-of-rheumatoid-arthritis-psoriatic-arthritis-and-axial-spondyloarthritis/qrheumatol.galenos.2023.57966

UPADACITINIB IN ACTION: EFFICACY AND SAFETY IN ... The results showed that the ACR20 response rates at week 12 were higher in patients receiving UPA at both doses (76% and 77% for UPA 15 and UPA 30, respectively) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03178487

NCT03178487 | A Study Evaluating the Safety and Efficacy ... The purpose of this study is to evaluate the safety and efficacy of upadacitinib in participants with active ankylosing spondylitis (AS) who have had an ...