A Study of SPY072 in Rheumatic Disease

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

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:

• Positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at Screening, OR
• 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 csDMARD treatment; AND/OR
• ≤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:

• BASDAI ≥4, AND
• 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:

• 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 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 NSAID treatment; AND
• ≥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