Psoriatic Arthritis, Spondyloarthritis, Axial
Conditions
Brief summary
A Randomized, Placebo-controlled, Multicenter, Study to Evaluate the Impact of Upadacitinib on Spondyloarthritis Outcomes in Patients with Active Psoriatic Arthritis (UP-SPOUT)
Interventions
15mg tablet once per day.
DRUGPlacebo
15mg tablet once per day.
Sponsors
CARE ARTHRITIS LTD.
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject ≥18 of age at the screening visit. 2. Subject must be able to understand and willing to adhere to all protocol requirements and voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures. 3. Diagnosis of PsA by their treating rheumatologist. 4. Classification of PsA according to the CASPAR criteria19: Inflammatory articular disease (joint, spine, or entheseal) AND at least 3 points of the following categories: a) Evidence of psoriasis: (Score for one of the following) i) Current psoriasis - 2 points (Psoriatic skin or scalp disease present today as judged by a dermatologist or rheumatologist) ii) Personal history of psoriasis - 1 point (A history of psoriasis that may be obtained from the subject, family physician, dermatologist, rheumatologist, or other qualified health care provider) iii) Family history of psoriasis - 1 point (A history of psoriasis in a first- or second-degree relative according to subject report) b) Psoriatic nail dystrophy - 1 point i) Typical psoriatic nail dystrophy, including onycholysis, pitting, and hyperkeratosis, observed on current physical examination c) A negative test for rheumatoid factor - 1 point i) By any method except latex, but preferably by enzyme-linked immunosorbent assay (ELISA) or nephelometry, according to the local laboratory reference range d) Dactylitis: (Score for 1 of the following) i) Current dactylitis - 1 point (Swelling of an entire digit) ii) History of dactylitis - 1 point (A history of dactylitis recorded by a rheumatologist) e) Radiologic evidence of juxta-articular new bone formation - 1 point i) Ill-defined ossification near joint margins (but excluding osteophyte formation) on plain radiographs of the hand or foot. 5. Evidence of axial involvement (e.g., active inflammation, structural changes) that has been demonstrated by previous imaging techniques (e.g., radiography, MRI, CT), is considered indicative of axial disease by central reader assessment (2 readers and adjudicator). 6. Screening/baseline MRI demonstrates definite active inflammation on MRI of SIJ and/or spine (ASAS definition of positive MRI and ≥4 SIJ quadrants with BME and/or ≥4 vertebral units with BME (in the absence of degenerative disc disease at those discovertebral units with BME)) as determined by central readers. 7. Presence of chronic back pain in the 3 months prior to screening. 8. Active disease as defined by a BASDAI value of ≥4 and TBP score of ≥4 (on a 0-10 NRS scale) at screening and baseline. 9. History of an inadequate response to at least two different NSAIDs over a period of 4 weeks in total at the maximum recommended or tolerated doses, or intolerance/contraindication (e.g., allergic reaction, gastrointestinal symptoms or signs, severe arterial hypertension, etc.) for NSAIDs. 10. For all females of child-bearing potential: must not have a positive serum pregnancy test at the Screening Visit and must have a negative urine pregnancy test at Baseline prior to the first dose of study drug (local practices may require serum pregnancy testing at Baseline). Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥3 days later to document continued lack of a positive result (unless prohibited by local requirements). 1. Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control that is effective from Study Day 1 through at least 30 days after the last dose of study drug (local practices may require 2 methods of birth control). Female subjects of non-childbearing potential do not need to use birth control. 2. Females must not be pregnant, breastfeeding, or considering becoming pregnant during the study and for approximately 30 days after the last dose of study drug. Females must commit to one of the following methods of highly effective birth control: * Combined (estrogen- and progestogen-containing) hormonal birth control (oral, intravaginal, transdermal, injectable) associated with inhibition of ovulation initiated at least 30 days prior to study baseline. * Progestogen-only hormonal birth control (oral, injectable, implantable) associated with inhibition of ovulation initiated at least 30 days prior to study baseline. * Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a hysterosalpingogram confirms success of the procedure) (For Japan: only bilateral tubal ligation). * Intrauterine device (IUD). * Intrauterine hormone-releasing system (IUS). * Vasectomized sexual partner (the partner has received medical confirmation of the surgical success of the vasectomy and is the sole sexual partner of the trial subject). * Practice true abstinence (unless not acceptable per local practices), defined as: refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable). 11. If required per local practices, females of childbearing potential must commit to using 2 methods of contraception (either 2 highly effective methods or 1 highly effective method combined with 1 effective method). Effective methods of birth control are the following: * Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, initiated at least 30 days prior to baseline. * Male or female condom with or without spermicide. * Cap, diaphragm, or sponge with spermicide. * A combination of male condom with a cap, diaphragm, or sponge with spermicide (double barrier method). * In questionable cases of menopausal status, a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/l and estradiol below 30 pg/ml is confirmatory. 12. Subjects who are regularly taking NSAIDs or analgesics (including mild opioids) as part of their PsA therapy are required to be on a stable dose/dose regimen for at least 14 days prior to the baseline visit. If entering the study on concomitant tramadol, combination of acetaminophen/paracetamol and codeine or combination of acetaminophen/paracetamol and hydrocodone, and/or non-opioid analgesics, subject must be on stable dose(s) for at least 14 days prior to the baseline Visit. However, subject must not have used opioid analgesics (except for combination of acetaminophen/paracetamol and codeine or combination of acetaminophen/paracetamol and hydrocodone which are allowed) within 14 days prior to the BL Visit. 13. Subjects taking oral corticosteroids must be on an average daily and stable dose of ≤10mg/day prednisone or equivalent for at least 14 days prior to the baseline visit. 14. Subjects taking topical therapies (e.g., topical JAKi, salicylic acid preparations, corticosteroids, retinoids) are allowed, but must be on a stable dose at least 4 weeks prior to the BL visit. 15. Subjects entering the study on the following concomitant csDMARDs must be on a stable dose as indicated below for at least 28 days prior to the baseline Visit (in case of Leflunomide washout must be either 8 weeks or 4 weeks with a standard cholestyramine wash-out). A combination of up to 2 background csDMARDs is allowed EXCEPT the combination of methotrexate (MTX) and leflunomide. * MTX (≤ 25 mg/week); or * Sulfasalazine (SSZ) (≤ 3 g/day); or * Hydroxychloroquine (≤ 400 mg/day); or * Chloroquine (≤ 250 mg/day); or * Leflunomide (≤ 20 mg/day); or * Apremilast (≤ 60 mg/day) 16. Subjects must have been treated for ≥ 3 consecutive months prior to the study entry with DMARD therapy (including csDMARD and/or bDMARD) and/or for ≥4 weeks of NSAID therapy (if csDMARDs are not indicated for their axial disease, in accordance with local product label for PSA, or nr-axSpA/AS for the subset with purely axial disease), but continue to exhibit active SpA, or had to discontinue previous DMARD and/or NSAID treatment due to intolerability or toxicity, irrespective of treatment duration . 1. Subjects recruited in Europe: Subjects must have previously been treated with one or more DMARD (csDMARD as defined in inclusion criterion 15, and/or bDMARD) and deemed to be inadequate responders and/or intolerant. 2. Subjects recruited in the US: Subjects must be TNFi-IR. In this study, an IR to TNFi therapy will be defined as patients who discontinue TNFi due to lack of efficacy based on the investigators' assessment or intolerance (irrespective of treatment duration). 3. Subjects recruited in Canada: Subjects must have previously been treated with one or more DMARD (csDMARD as defined in inclusion criterion 15, and/or bDMARD) and deemed to be inadequate responders and/or intolerant. * Up to 20 patients presenting with purely axial disease and current psoriasis (at the time of screening) may be included in the study. These patients may have had a past history of joint involvement, but do not currently require csDMARD therapy. In order to be deemed eligible, these patients must meet both the ASAS Classification Criteria for axSpA and the CASPAR criteria, as well as all other inclusion/
Exclusion criteria
, including inadequate response to 2 NSAIDs (inclusion criterion #9 - all countries), bioDMARD (Canada), and TNFi (US). The ASAS Classification Criteria for axSpA are provided in Appendix A. 17. If subjects are currently taking bioDMARD therapy, they may be recruited after an appropriate wash-out period of bioDMARD prior to the screening MRI. Prior exposure to a bioDMARD is allowed for no more than 75 subjects, and prior exposure to a 2nd bioDMARD is allowed for no more than 30 subjects (one bioDMARD must include TNFi for US patients). Washout periods are as follows: 4 weeks for Etanercept, 8 weeks for Infliximab, 10 weeks for Adalimumab, Golimumab, Certolizumab and Ixekizumab, 12 weeks for Ustekinumab, Secukinumab, Guselkumab, and Abatacept, and 20 weeks for Risankizumab. However, subjects should not stop their previous successful biological therapy only to be included in this study. For patients intolerant to bioDMARD and not on such treatment a washout period may not be necessary.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the (SPARCC) MRI inflammation score (for SIJ and spine) at 12 weeks of therapy with upadacitinib vs placebo in the DMARD-IR (conventional and/or biologic) subgroup | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) at Week 12 with upadacitinib vs placebo in the DMARD-IR (conventional and/or biologic) subgroup | 12 weeks |
| Change from Baseline in BASDAI at Week 12 with upadacitinib vs placebo in the DMARD-IR (conventional and/or biologic) subgroup | 12 weeks |
| Change from baseline in the (SPARCC) MRI inflammation score (for SIJ and spine) at 12 weeks of therapy with upadacitinib vs placebo in the overall population (NSAID-IR, c-DMARD-IR and and bio-DMARD-IR) | 12 weeks |
| Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) at Week 12 with upadacitinib vs placebo in the overall population (NSAID-IR, c-DMARD-IR and and bio-DMARD-IR) | 12 weeks |
| Change from Baseline in BASDAI at Week 12 with upadacitinib vs placebo in the overall population (NSAID-IR, c-DMARD-IR and and bio-DMARD-IR) | 12 weeks |
| Incidence of Adverse Events (AEs), AEs leading to withdrawal from study drug, and serious AEs (SAEs). | 28 weeks |
Countries
Canada, United States
Contacts
CONTACTAmanda Carapellucci
CONTACTRana Dadashova
PRINCIPAL_INVESTIGATORWalter Maksymowych, Dr.
CARE ARTHRITIS LTD.
Outcome results
None listed