A Study to Evaluate Efficacy and Safety of Upadacitinib in Adults With Axial Spondyloarthritis (SELECT-AXIS 2)

AbbVie

Status and phase: Active, not recruiting; Phase 3

Conditions: Spondyloarthritis

Treatments: Drug: Placebo; Drug: Upadacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04169373

M19-944

2022-501018-78-00 (Other Identifier)

Details and patient eligibility

About

This protocol includes 2 standalone studies with randomization, data collection, analysis and reporting conducted independently.

The main objectives of this protocol are:

• To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adults with active axial spondyloarthritis (axSpA) including biologic disease-modifying antirheumatic drug inadequate responders (bDMARD-IR) ankylosing spondylitis (AS) (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2).
• To assess the safety and tolerability of upadacitinib in adults with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2).
• To evaluate the safety and tolerability of upadacitinib in extended treatment in adult participants with active axSpA including bDMARD-IR AS who have completed the Double-Blind Period (Study 1) and nr-axSpA who have completed the Double-Blind Period (Study 2).
• To evaluate the maintenance of disease control after withdrawal of upadacitinib.

Full description

Study 1 (bDMARD-IR AS) is comprised of a 14-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 90-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day Follow-Up Visit (F/U Visit).

Study 2 (nr-axSpA) is comprised of a 52-week randomized, double-blind, parallel-group, placebo-controlled period (the Double-Blind Period); a 52-week open-label, long-term extension period (the Open-Label Extension Period); and a 30-day F/U Visit.

In the Double-Blind Period for both studies, participants are randomized in a 1:1 ratio to receive either upadacitinib or placebo once daily (QD).

Participants in the placebo group switch to upadacitinib 15 mg QD at Week 14 in the Open-Label Extension Period for Study 1 (bDMARD-IR AS) and Week 52 in the Open-Label Extension Period for Study 2 (nr-axSpA).

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

Study M19-944 protocol uses a common screening platform for determining eligibility into Study 1 and Study 2. Each study has its own objectives, hypothesis testing, randomization, data collection, and adequate power for primary and secondary endpoints. Analysis and reporting are conducted separately and independently for each study.

Enrollment: 734 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Study 1:

  • Must have a clinical diagnosis of ankylosing spondylitis (AS) and meet the modified New York Criteria for AS,
  • Must not have total spinal ankylosis
  • Must have been previously exposed to 1 or 2 bDMARDs (at least 1 tumor necrosis factor [TNF] inhibitor or 1 interleukin [IL]-17 inhibitor [IL-17i]), and must have discontinued the bDMARD therapy due to either lack of efficacy (after at least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance (irrespective of treatment duration). Prior exposure to two bDMARDs was allowed for no more than 30% of patients; among patients with prior exposure to two bDMARDs, a lack of efficacy to one bDMARD and intolerance to another was permitted, but a patient could not have a lack of efficacy to two bDMARDs

• Study 2:

  • Must have a clinical diagnosis of nr-axSpA fulfilling the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS
  • Must have objective signs of active inflammation consistent with axSpA on magnetic resonance imaging (MRI) of sacroiliac (SI) joints or based on high sensitivity C-reactive protein (hsCRP) > the upper limit of normal (ULN).
  • Prior treatment with at most one bDMARD (either TNF inhibitor or IL-17i) is allowed for at least 20% but no more than 35% of enrolled patients who had to discontinue the prior bDMARD due to either lack of efficacy (after ≥ 12 weeks at an adequate dose) or intolerance (regardless of treatment duration).

• Must have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at the Screening and Baseline Visits.

• Must have a Total Back Pain score ≥ 4 based on a 0 - 10 numerical rating scale at the Screening and Baseline Visits.

• Has had an inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or has an intolerance to or contraindication for NSAIDs as defined by the Investigator.

Exclusion criteria

• Must not have been exposed to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib [Rinvoq®], tofacitinib [Xeljanz®], baricitinib [Olumiant®], filgotinib, ruxolitinib [Jakafi®], abrocitinib [PF-04965842], and peficitinib [Smyraf®]).
• Prior bDMARD therapy must be washed out.
• Participant must not have a history of an allergic reaction or significant sensitivity to constituents of the study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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734 participants in 4 patient groups, including a placebo group

Study 1: Upadacitinib 15 mg

Experimental group

Description:

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).

Treatment:

Drug: Upadacitinib

Study 1: Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Upadacitinib

Drug: Placebo

Study 2: Upadacitinib 15 mg

Experimental group

Description:

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).

Treatment:

Drug: Upadacitinib

Study 2: Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Upadacitinib

Drug: Placebo