A Study of SPY072 in Rheumatic Disease

Not Applicable

Recruiting

• Conditions: Rheumatoid Arthritis; Rheumatic Joint Disease; Psoriatic Arthritis; Axial Spondyloarthritis; Rheumatic Diseases; AxSpA; PsA (Psoriatic Arthritis); Rheumatologic Disease
• Interventions: Drug: SPY002-072; Drug: Placebo

• Registration Number: NCT07148414
• Lead Sponsor: Spyre Therapeutics, Inc.

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

Study Timeline

• Study Start: 2025-08-21
• Study First Submitted: 2025-08-21
• Study First Submitted QC: 2025-08-21
• Study First Posted: 2025-08-29
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-05
• Last Update Posted: 2025-09-12
• Primary Completion: 2026-10-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 285

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. Previous radiographs with bony erosions in hands or feet consistent with RA

• Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to one of the following:

  1. ≥1 csDMARD treatment; OR
  2. 1 bDMARD or 1 tsDMARD treatment (a total of 2 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 one of the following:

  1. 2 different NSAIDs given at the maximum tolerated dose for ≥4 weeks or intolerant to or has a contraindication to NSAID therapy; OR
  2. 1 bDMARD (anti-TNF or anti-IL-17) or 1 tsDMARD treatment at an approved dose for ≥12 weeks (a total of 2 bDMARDs and/or tsDMARDs is exclusionary)

For psoriatic arthritis:

• 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

• In adequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to one of the following:

  1. ≥1 NSAID treatment; AND
  2. ≥1 csDMARD treatment; OR
  3. 1 bDMARD or 1 tsDMARD treatment (a total of 2 bDMARDs and/or tsDMARDs is exclusionary)

Exclusion Criteria

• Inadequate response to ≥2 or more bDMARDs and/or tsDMARDs
• Other autoimmune, rheumatologic, inflammatory diseases or pain-amplification syndromes that might confound the evaluations of efficacy of SPY072

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rheumatoid Arthritis, Dose Regimen 1	SPY002-072	Participants will receive double-blind dosing regimen 1 of SPY072
Rheumatoid Arthritis, Dose Regimen 2	SPY002-072	Participants will receive double-blind dosing regimen 2 of SPY072
Psoriatic Arthritis	SPY002-072	Participants will receive double-blind dose of SPY072
Axial Spondyloarthritis	SPY002-072	Participants will receive double-blind dose of SPY072
Rhematoid Arthritis Placebo	Placebo	Participants will receive matching placebo
Psoriatic Arthritis Placebo	Placebo	Participants will receive matching placebo
Axial Spondyloarthritis Placebo	Placebo	Participants will receive matching placebo

Primary Outcome Measures

Name	Time	Method
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 indicates greater disease severity.
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 indicates higher 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 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 Outcome Measures

Name	Time	Method
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 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.

Trial Locations

Locations (4)

Site 108; 🇺🇸 Tujunga, California, United States

Site 101; 🇺🇸 Brookline, Massachusetts, United States

Site 103; 🇺🇸 Tomball, Texas, United States

Site 102; 🇺🇸 Tomball, Texas, United States