Axial Spondyloarthritis (AxSpA)
Conditions
Keywords
comparative effectiveness, axial spondyloarthritis, secukinumab, upadacitinib
Brief summary
The purpose of this study is to determine the feasibility of conducting a pragmatic trial of IL-17i versus JAKi in adults with axial spondyloarthritis (axSpA) who have failed at least one tumor necrosis factor-alpha inhibitor (TNFi), to estimate the effectiveness of IL-17i versus JAKi at 16 weeks and to determine additional effectiveness measures, safety, and treatment persistence of IL-17i versus JAKi
Interventions
DRUGSecukinumab (IL-17i )
Secukinumab is a fully humanized monoclonal antibody targeting interleukin-17A. Secukinumab will be given as a prefilled syringe or autoinjector for subcutaneous administration. Dosing is 150 mg subcutaneously at weeks 0, 1, 2, 3, and 4 followed by 150mg every 4 weeks thereafter for a total of 16 weeks.
DRUGUpadacitinib (JAKi)
Upadacitinib is an oral selective inhibitor of janus kinase 1 (JAK1). Participants will take upadacitinib 15mg orally once daily for 16 weeks.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* fulfill ASAS classification criteria for axSpA and/or modified New York classification criteria for AS * Active axSpA (ASDAS ≥ 2.1 and/or BASDAI ≥ 4) * Failure of or intolerance to ≥1 TNF * Participants of reproductive potential must agree to use any form of effective contraception during the study period, in accordance with standard clinical practice and FDA labeling for the assigned study medication * Ability to provide informed consent
Exclusion criteria
* Previously received an IL-17i or JAKi * Active infection requiring antimicrobials * Contraindications to either treatment arm: * Inflammatory bowel disease (IBD)- Crohn's disease or Ulcerative Colitis * Active cancer or cancer remission within the past 3 years (apart from non-melanoma skin cancer (NMSC) and cervical intraepithelial neoplasia (CIN) * History of stroke, heart attack, or blood clots (venous or arterial) * Cirrhosis * End-stage renal disease (GFR \<15) or dialysis * Human Immunodeficiency Virus (HIV) positive * Pregnant or lactating * Concomitant use of other biologic or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility as determined by ≥80% retention of randomized participants | end of treatment (week 16) | — |
| Feasibility as determined by ≥90% completeness of primary clinical data | end of treatment (week 16) | — |
| Change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) reported as a mean (SD) | Baseline, week 16 | This is a 4 item questionnaire and one lab result (CRP). The first 4 questions are scored from 0-10. The result is a single numerical score, typically ranging from about 0 to 6, with higher scores indicating more active disease. |
| Feasibility as determined by enrollment of ≥60% of eligible patients | end of treatment (week 16) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients showing an improvement of ≥1.1 and ≥2.0 on the ASDAS score | end of treatment (week 16) | — |
| Percentage of patients showing an improvement of ≥1.1 and ≥2.0 on the ASDAS score | end of treatment (week 16) | — |
| Number of participants in the different categories of disease activity as assessed by the ASDAS | end of treatment (week 16) | The ASDAS categories are: Inactive disease (\<1.3) Low disease activity (1.3-\<2.1) High disease activity (2.1-3.5) Very high disease activity (\>3.5) |
| Change in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured as a mean (SD) | Baseline, Week 16 | The BASDAI is a self-administered 6-question instrument covering fatigue, spinal (axial) pain, peripheral joint pain/swelling, localized tenderness (enthesitis), and the severity and duration of morning stiffness. Each question is scored 0-10. The final result is a single numerical score ranging from 0 to 10, with higher scores indicating more active disease |
| Change in fatigue as assessed by BASDAI Q1 measured as a mean (SD) | Baseline, week 16 | Fatigue will be assessed using Question 1of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = none and 10 = very severe. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in fatigue), while a positive change indicates worsening fatigue |
| Change in total back pain as assessed by BASDAI Q2 measured as a mean (SD) | Baseline, week 16 | Total back pain will be assessed using Question 2 of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = none and 10 = very severe. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in pain), while a positive change indicates worsening pain |
| Change in mean stiffness severity as assessed by BASDAI Q5 measured as a mean (SD) | Baseline, week 16 | Stiffness severity will be assessed using Question 5 of the BASDAI and this will be scored on a 0-10 numerical rating scale, where 0 = no stiffness and 10 = most severe stiffness. The outcome will be reported as the mean (SD). A negative change indicates improvement (reduction in stiffness)while a positive change indicates worsening stiffness |
| Change in physical functioning as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) measured as a mean (SD) | Baseline, week 16 | The Bath Ankylosing Spondylitis Functional Index (BASFI) is a self-administered 10-item questionnaire. It comprises 8 questions on function specific to axSpA and 2 questions on the patient's ability to cope with everyday life, each scored 0-10 on a visual analog scale. The final BASFI score is the mean of the 10 items, ranging from 0 (good function) to 10 (poor function), with higher scores indicating worse physical function. |
| Number of participants who met the Assessment of SpondyloArthritis International Society 20% response (ASAS20) criteria | end of treatment (week 16 ) | A participant achieves an ASAS20 response if they have: ≥20% improvement and an absolute improvement of ≥1 unit (on a 0-10 scale) in at least 3 of the following 4 domains, with no worsening (≥20% and ≥1 unit) in the remaining domain. The four domains are: Patient global assessment Spinal pain Physical function (measured by BASFI) Inflammation (average of the two BASDAI morning stiffness questions) Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement. |
| Percentage (%) of participants who met the ASAS20 response criteria | end of treatment (week 16) | A participant achieves an ASAS20 response if they have: ≥20% improvement and an absolute improvement of ≥1 unit (on a 0-10 scale) in at least 3 of the following 4 domains, with no worsening (≥20% and ≥1 unit) in the remaining domain. The four domains are: Patient global assessment Spinal pain Physical function (measured by BASFI) Inflammation (average of the two BASDAI morning stiffness questions) Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement. |
| Number of participants who met the Assessment of SpondyloArthritis International Society 40% response (ASAS40) criteria | end of treatment (week 16) | A participant achieves an ASAS40 response if they have: ≥40% improvement and an absolute improvement of ≥2 units in at least 3 of the 4 domains, with No worsening in the remaining domain. Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement. |
| Percentage of participants who met the ASAS40 response criteria | end of treatment (week 16) | A participant achieves an ASAS40 response if they have: ≥40% improvement and an absolute improvement of ≥2 units in at least 3 of the 4 domains, with No worsening in the remaining domain. Higher percentages indicate a greater proportion of patients experienced clinically meaningful improvement. |
| Change in the impact of axSpA on health and functioning as assessed by the ASAS Health Index (ASAS HI) measured as a mean (SD) | Baseline, week 16 | The ASAS Health Index is a self-reported 17-item questionnaire assessing functioning, disability, and overall health in spondyloarthritis. Each item is answered dichotomously and scored 1 (agree) or 0 (do not agree), producing a summed total score ranging from 0 to 17, with higher scores indicating worse health/greater impairment. |
| Number of patients with improvement ≥3 on the ASAS HI score | end of treatment (week 16) | — |
| Percentage of patients with improvement ≥3 on the ASAS HI score | end of treatment (week 16) | — |
| Change in peripheral joint inflammation as assessed by the 44 Tender Joint Count (TJC44) measured as a mean(SD) | Baseline, week 16 | Tender Joint Count (TJC44); each of the 44 joints are scored as 0(not tender) or 1(tender) . The total score ranges from 0-44. Higher scored indicate more active peripheral arthritis. |
| Change in peripheral joint inflammation as assessed by the 44 Swollen Joint Count (SJC44) measured as a mean(SD) | Baseline, week 16 | Swollen Joint Count (SJC44): each of the 44 joints are scored as 0(Not swollen) or 1(Swollen). The total score ranges from 0-44. Higher scored indicate more active peripheral arthritis. |
| Change in peripheral joint inflammation assessed by the Disease Activity Index for Psoriatic Arthritis (DAPSA44) measured as a mean (SD) | Baseline, week 16 | The DAPSA44 is calculated as the simple sum of five components: the 44 Tender Joint Count (TJC44, 0-44), the 44 Swollen Joint Count (SJC44, 0-44), the patient's assessment of peripheral pain (0-10 numeric scale, using BASDAI Q3), the patient's global assessment of disease activity (0-10 numeric scale), and C-reactive protein (mg/dL). The result is a single continuous score, with higher scores indicating greater peripheral disease activity |
| Change in severity of enthesitis as assessed by the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) measured as a mean (SD) | Baseline, week 16 | The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) is an enthesitis index, in which 13 entheseal sites are examined for tenderness and each scored as 0 (no tenderness) or 1 (tenderness present). The total score ranges from 0 to 13, with higher scores indicating greater entheseal involvement. |
| Change in number of digits with active dactylitis as assessed by the Dactylitis Count measured as a mean(SD) | Baseline, week 16 | The simple dactylitis count assesses each of the 20 digits (10 fingers and 10 toes), scoring each as present (1) or absent (0) for dactylitis. The total score ranges from 0 to 20, with higher scores indicating a greater number of involved digits. |
| Number of patients who developed psoriasis after starting treatment | Baseline to week 16 | — |
| Percentage of patients who developed psoriasis after starting treatment | Baseline to week 16 | — |
| Number of patients who had an occurrence of acute anterior uveitis (AAU) episode since starting treatment | Baseline to week 16 | — |
| Percentage of patients who had an occurrence of acute anterior uveitis (AAU) since starting treatment | Baseline to week 16 | — |
| Number of patients who developed Inflammatory Bowel Disease (IBD) during treatment | Baseline to week 16 | — |
| Percentage of patients who developed Inflammatory Bowel Disease (IBD) during treatment | Baseline to week 16 | — |
| Number of patients who had an adverse event by category during treatment | Baseline to week 16 | Adverse event categories include: 1. Blood and lymphatic system disorders 2. Cardiac disorders 3. Ear and labyrinth disorders 4. Endocrine disorders 5. Eye disorders 6. Gastrointestinal disorders 7. General disorders and administration site conditions 8. Hepatobiliary disorders 9. Immune system disorders 10. Infections and infestation 11. Injury, poisoning and procedural complications 12. Lab abnormalities 13. Metabolism and nutrition disorders 14. Musculoskeletal and connective tissue disorders 15. Neoplasms benign, malignant and unspecified (incl cysts and polyps) 16. Nervous system disorders 17. Psychiatric disorders 18. Renal and urinary disorders 19. Reproductive system and breast disorders 20. Respiratory, thoracic and mediastinal disorders 21. Skin and subcutaneous tissue disorders 22. Vascular disorders |
| Percentage of patients who had an adverse event by category during treatment | from baseline to week 16 | Adverse event categories include: 1. Blood and lymphatic system disorders 2. Cardiac disorders 3. Ear and labyrinth disorders 4. Endocrine disorders 5. Eye disorders 6. Gastrointestinal disorders 7. General disorders and administration site conditions 8. Hepatobiliary disorders 9. Immune system disorders 10. Infections and infestation 11. Injury, poisoning and procedural complications 12. Lab abnormalities 13. Metabolism and nutrition disorders 14. Musculoskeletal and connective tissue disorders 15. Neoplasms benign, malignant and unspecified (incl cysts and polyps) 16. Nervous system disorders 17. Psychiatric disorders 18. Renal and urinary disorders 19. Reproductive system and breast disorders 20. Respiratory, thoracic and mediastinal disorders 21. Skin and subcutaneous tissue disorders 22. Vascular disorders |
| Change in Erythrocyte Sedimentation Rate (ESR) measured as a mean(SD) | Baseline, week 16 | Higher values generally indicate greater systemic inflammation. |
| Change in C-reactive Protein (CRP) measured as a mean(SD) | Baseline, week 16 | Higher values generally indicate greater inflammatory activity.. |
| Treatment persistence at week 16 | Week 16 | Treatment persistence is defined as a patient who remains on randomized therapy at week 16. |
| Percentage of participants in the different categories of disease activity as assessed by the ASDAS | end of treatment (week 16) | The ASDAS categories are: Inactive disease (\<1.3) Low disease activity (1.3-\<2.1) High disease activity (2.1-3.5) Very high disease activity (\>3.5) |
| Treatment persistence at week 52 | End of study (week 52) | Treatment persistence at week 52 is defined as patients who remain on randomized therapy at week 52 |
| Number of participants that have an ASDAS score of <2.1 and ≥2.1 | end of treatment (week 16) | — |
| Percentage of participants that have an ASDAS score of <2.1 and ≥2.1 | end of treatment (week 16) | — |
| Change in patient global disease activity measured as a mean (SD) | Baseline, week 16 | Disease activity is measured using a Numerical Rating Scale (NRS) from 0 (no disease) to 10 (very severe disease) |
Countries
United States
Contacts
CONTACTSavannah M Bowman, MD
CONTACTMark C Hwang, MD
PRINCIPAL_INVESTIGATORSavannah M Bowman, MD
The University of Texas Health Science Center, Houston
Outcome results
None listed