A Study of SPY072 in Rheumatic Disease (SKYWAY-RD)

June 3, 2026 updated by: Spyre Therapeutics, Inc.

Phase 2 Study to Assess the Efficacy and Safety of SPY002-072 in Adults With Moderately to Severely Active Rheumatologic Disease

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

285

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
    • Lovech
      • Lovech, Lovech, Bulgaria, 5500
        • Site 503
    • Pleven
      • Pleven, Pleven, Bulgaria, 5803
        • Site 502
    • Plovdiv
      • Plovdiv, Plovdiv, Bulgaria, 4000
        • Site 506
      • Plovdiv, Plovdiv, Bulgaria, 4003
        • Site 505
    • Varna
      • Varna, Varna, Bulgaria, 9000
        • Site 504
  • Czechia
    • Hlučín
      • Hlučín, Hlučín, Czechia, 748 01
        • Site 706
    • Ostrava-město
      • Moravská Ostrava, Ostrava-město, Czechia, 702 00
        • Site 702
    • Pardubice Region
      • Pardubice, Pardubice Region, Czechia, 530 02
        • Site 704
    • Praha, Hlavní Mesto
      • Prague, Praha, Hlavní Mesto, Czechia, 130 00
        • Site 705
      • Prague, Praha, Hlavní Mesto, Czechia, 140 00
        • Site 703
    • Zlín
      • Uherské Hradiště, Zlín, Czechia, 68601
        • Site 701
  • Georgia
      • Batumi, Georgia, 6010
        • Site 308
      • Kutaisi, Georgia, 4600
        • Site 302
      • Tbilisi, Georgia, 0186
        • Site 306
    • K'alak'i T'bilisi
      • Tbilisi, K'alak'i T'bilisi, Georgia, 0102
        • Site 303
      • Tbilisi, K'alak'i T'bilisi, Georgia, 0112
        • Site 304
      • Tbilisi, K'alak'i T'bilisi, Georgia, 0159
        • Site 301
      • Tbilisi, K'alak'i T'bilisi, Georgia, 0172
        • Site 307
      • Tbilisi, K'alak'i T'bilisi, Georgia, 0186
        • Site 305
  • Moldova
      • Chisinau, Moldova, MD-2025
        • Site 201
      • Chisinau, Moldova, MD-2025
        • Site 202
  • Poland
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 30-363
        • Site 401
    • Lubusz Voivodeship
      • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
        • Site 407
    • Lódzkie
      • Lodz, Lódzkie, Poland, 91-363
        • Site 404
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-677
        • Site 403
    • Opole Voivodeship
      • Opole, Opole Voivodeship, Poland, 45-819
        • Site 402
    • Pomeranian Voivodeship
      • Gdynia, Pomeranian Voivodeship, Poland, 81-384
        • Site 406
      • Warszawa, Pomeranian Voivodeship, Poland, 00-874
        • Site 405
    • Warmian-Masurian Voivodeship
      • Elblag, Warmian-Masurian Voivodeship, Poland, 82-300
        • Site 408
  • Spain
    • A Coruña
      • A Coruña, A Coruña, Spain, 15006
        • Site 602
    • Cadiz
      • Chiclana de la Frontera, Cadiz, Spain, 11139
        • Site 604
    • Madrid
      • Santander, Madrid, Spain, 39008
        • Site 601
    • Sevilla
      • Seville, Sevilla, Spain, 41010
        • Site 603
  • Ukraine
    • Chernihiv Oblast
      • Chernihiv, Chernihiv Oblast, Ukraine, 14029
        • Site 809
    • Kyiv Oblast
      • Kyiv, Kyiv Oblast, Ukraine, 02091
        • Site 813
      • Kyiv, Kyiv Oblast, Ukraine, 03049
        • Site 806
      • Kyiv, Kyiv Oblast, Ukraine, 04050
        • Site 804
      • Kyiv, Kyiv Oblast, Ukraine, 2125
        • Site 803
      • Kyiv, Kyiv Oblast, Ukraine, 4106
        • Site 805
    • Lviv Oblast
      • Lviv, Lviv Oblast, Ukraine, 79044
        • Site 807
    • Ternopil Oblast
      • Ternopil, Ternopil Oblast, Ukraine, 46002
        • Site 808
      • Ternopil, Ternopil Oblast, Ukraine, 46002
        • Site 810
    • Vinnytsia Oblast
      • Vinnytsia, Vinnytsia Oblast, Ukraine, 21028
        • Site 801
      • Vinnytsia, Vinnytsia Oblast, Ukraine, 21029
        • Site 802
    • Vinnytska
      • Vinnytsia, Vinnytska, Ukraine, 21000
        • Site 812
    • Zhytomyr Oblast
      • Zhytomyr, Zhytomyr Oblast, Ukraine, 10002
        • Site 811
  • United States
    • Arizona
      • Avondale, Arizona, United States, 85392
        • Site 113
      • Tucson, Arizona, United States, 85748
        • Site 118
    • California
      • Chula Vista, California, United States, 91910
        • Site 114
      • Covina, California, United States, 91722
        • Site 111
      • Tujunga, California, United States, 91042
        • Site 108
      • Upland, California, United States, 91786
        • Site 112
      • Whittier, California, United States, 90602
        • Site 107
    • Florida
      • Aventura, Florida, United States, 33180
        • Site 115
      • Hialeah, Florida, United States, 33016
        • Site 109
      • Ormond Beach, Florida, United States, 32174
        • Site 106
      • Tampa, Florida, United States, 33614
        • Site 110
    • Illinois
      • Willowbrook, Illinois, United States, 60527
        • Site 116
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Site 119
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Site 104
    • Texas
      • Corpus Christi, Texas, United States, 78404
        • Site 105
      • Irving, Texas, United States, 75039
        • Site 120
      • Tomball, Texas, United States, 77375
        • Site 103
      • Tomball, Texas, United States, 77377
        • Site 102

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rheumatoid Arthritis, Dose Regimen 1
Participants will receive double-blind dosing regimen 1 of SPY072
Drug: SPY002-072
Experimental
Other Names:
  • SPY072
Experimental: Rheumatoid Arthritis, Dose Regimen 2
Participants will receive double-blind dosing regimen 2 of SPY072
Drug: SPY002-072
Experimental
Other Names:
  • SPY072
Experimental: Psoriatic Arthritis
Participants will receive double-blind dose of SPY072
Drug: SPY002-072
Experimental
Other Names:
  • SPY072
Experimental: Axial Spondyloarthritis
Participants will receive double-blind dose of SPY072
Drug: SPY002-072
Experimental
Other Names:
  • SPY072
Placebo Comparator: Rhematoid Arthritis Placebo
Participants will receive matching placebo
Drug: Placebo
Matching Placebo
Placebo Comparator: Psoriatic Arthritis Placebo
Participants will receive matching placebo
Drug: Placebo
Matching Placebo
Placebo Comparator: Axial Spondyloarthritis Placebo
Participants will receive matching placebo
Drug: Placebo
Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rheumatoid Arthritis: Change from baseline in Disease Activity Score in 28 joints (c-reactive protein) (DAS-CRP)
Time Frame: 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.
Week 12
Axial Spondyloarthritis: Change from baseline in Ankylosing Spondylitis Disease Activity Score (ADAS)
Time Frame: 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.
Week 16
Psoriatic Arthritis: Proportion of participants who achieve an American College of Rheumatology 20 Response Criteria (ACR20) response
Time Frame: 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.
Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Axial Spondyloarthritis: Proportion of participants who achieve an Assessment of Spondyloarthritis International Society (40% improvement) (ASAS40) response
Time Frame: 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.
Week 16
Psoriatic Arthritis: Change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA)
Time Frame: 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.
Week 16
Rheumatoid Arthritis: Proportion of participants who achieve an ACR20 response
Time Frame: 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.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spyre Therapeutics, Inc.

Investigators

  • Study Director: SKYWAY-RD Study Director, Spyre Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 21, 2025

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

August 21, 2025

First Submitted That Met QC Criteria

August 21, 2025

First Posted (Actual)

August 29, 2025

Study Record Updates

Last Update Posted (Actual)

June 5, 2026

Last Update Submitted That Met QC Criteria

June 3, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPY002-072-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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