Axial Spondyloarthritis, AxSpA, PsA (Psoriatic Arthritis), Psoriatic Arthritis, Rheumatic Diseases, Rheumatic Joint Disease, Rheumatoid Arthritis, Rheumatologic Disease
Conditions
Brief summary
This is a multi-center, double-blind, placebo-controlled, Phase 2, proof-of-concept basket study with the goal of assessing the efficacy and safety of SPY072 compared to placebo in adults (aged ≥18 years) with rheumatic disease (RD).
Detailed description
The basket study comprises of substudies in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatric arthritis (PsA) as follows: * RA substudy: Moderately to severely active RA despite treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biologic disease modifying anti-rheumatic drugs (bDMARDs), or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) * axSpA substudy: Moderately to severely active axSpA despite treatment with non-steroidal anti-inflammatory drugs (NSAIDS), bDMARDs, or tsDMARDs * PsA substudy: Moderately to severely active PsA despite treatment with NSAIDs, csDMARDs, bDMARDs, or tsDMARDs
Interventions
DRUGSPY002-072
Experimental
DRUGPlacebo
Matching Placebo
Sponsors
Spyre Therapeutics, Inc.
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
For rheumatoid arthritis: * Moderate-to-severely active RA as defined by the presence of ≥4 swollen joints (based on 28 joint count) and ≥4 tender joints (based on 28 joint count) at Screening and Day 1. * Documentation of ≥1 of the following: 1. Positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at Screening, OR 2. Radiology report documenting bony erosions in hands or feet consistent with RA on previous radiographs * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. ≥1 csDMARD treatment; AND/OR 2. ≤2 classes of bDMARD/tsDMARD treatment (\>2 classes of bDMARDs and/or tsDMARDs is exclusionary) For axial spondyloarthritis: * Moderate-to-severely active axSpA defined by BOTH of the following at Screening AND Day 1: 1. BASDAI ≥4, AND 2. Back pain ≥4 (from BASDAI Item 2) * hsCRP greater than the ULN per the central laboratory at Screening * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. 2 different NSAIDs given at the maximum tolerated dose for ≥4 weeks or intolerant to or has a contraindication to NSAID therapy; AND/OR 2. ≤2 classes of bDMARD (anti-TNF or anti-IL-17)/tsDMARD at an approved dose for ≥12 weeks (\>2 classes of bDMARDs/tsDMARDs is exclusionary) For psoriatic arthritis: * Screening and Day 1 TJC ≥3 out of 68 and SJC ≥3 out of 66 (dactylitis counts as 1 joint each) * ≥1 active plaque psoriasis lesion and/or a documented history of psoriasis * Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: 1. ≥1 NSAID treatment; AND 2. ≥1 csDMARD treatment; AND/OR ≤2 classes of bDMARD/tsDMARD treatment (\>2 classes of bDMARDs and/or tsDMARDs is exclusionary)
Exclusion criteria
* Inadequate response to \>2 classes of bDMARDs/tsDMARDs * Other autoimmune, rheumatologic, inflammatory diseases or pain-amplification syndromes that might confound the evaluations of efficacy of SPY072
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rheumatoid Arthritis: Change from baseline in Disease Activity Score in 28 joints (c-reactive protein) (DAS-CRP) | Week 12 | The score is calculated based on the number of tender and swollen joints out of 28 assessed (TJC28 and SJC28), a measure of inflammation in the blood (c-reactive protein, CRP), and the subject's overall assessment of their health (patient global assessment). Scores range from 0-10. Higher scores indicate greater disease activity. |
| Axial Spondyloarthritis: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ADAS) | Week 16 | The score combines 5 disease activity variables (back pain, duration of morning stiffness, patient global assessment of disease activity, peripheral pain/swelling and measure of inflammation) to measure disease activity. Lowest score is 0.6 and increases as disease worsens. Higher scores indicate greater disease activity. |
| Psoriatic Arthritis: Proportion of participants who achieve an American College of Rheumatology 20 Response Criteria (ACR20) response | Week 16 | The proportion of subjects who achieve at least 20% improvement in tender and swollen joint counts (TJC and SJC), and at least 20% improvement in 3 out of 5 other disease activity measures (patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire, and measure of inflammation) will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rheumatoid Arthritis: Proportion of participants who achieve an ACR20 response | Week 12 | The proportion of subjects who achieve at least 20% improvement in tender and swollen joint counts, and at least 20% improvement in 3 out of 5 other disease activity measures will be assessed. |
| Axial Spondyloarthritis: Proportion of participants who achieve an Assessment of Spondyloarthritis International Society (40% improvement) (ASAS40) response | Week 16 | The proportion of subjects who achieve at least 40% improvement in at least 3 out of 4 key domains related to disease severity (patient global assessment of disease activity, back pain, physical function, inflammation) while not experiencing worsening in the remain domain will be assessed. |
| Psoriatic Arthritis: Change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) | Week 16 | The sum of 5 key disease variables (tender joint count, swollen joint count, patient pain assessment, patient global assessment of disease activity, and C-reactive protein) will be assessed. Scores range from 0.1 to 86. Higher score indicates higher disease activity. |
Countries
Bulgaria, Czechia, Georgia, Moldova, Poland, Spain, Ukraine, United States
Contacts
STUDY_DIRECTORSKYWAY-RD Study Director
Spyre Therapeutics
Outcome results
None listed