Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

Ubicaciones

Organizacion Medica de Investigacion (OMI) /ID# 214557

Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma de Buenos Aires, Argentina

Centro de Enfermedades del Hígado y Aparato Digestivo /ID# 214556

Rosario, Santa Fe Province, Argentina

Instituto CAICI /ID# 215242

Rosario, Santa Fe Province, Argentina

Centro de Investigaciones Medicas Tucuman /ID# 214559

San Miguel de Tucumán, Tucumán Province, Argentina

Hospital Cordoba /ID# 215846

Córdoba, Argentina

Instituto Medico Strusberg /ID# 215239

Córdoba, Argentina

Cimer /Id# 215240

San Miguel de Tucumán, Argentina

A Phase 3 Randomized, Placebo-Controlled, Double-Blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult Subjects With Axial Spondyloarthritis Followed by a Remission-Withdrawal Period