SPY002-072 in Adults with Moderately to Severely Active Rheumatologic Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Spyre Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

18 Dec 2025 → ongoing

Decision date (initial)

2025-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Spyre Therapeutics, Inc.

External identifiers

EU CT number

2025-521791-63-00

WHO UTN

U1111-1320-9934

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Pharmacodynamic, Efficacy, Pharmacokinetic, Pharmacogenomic

RA Substudy:
To assess the efficacy of SPY072 compared with placebo in reducing the disease activity of rheumatoid arthritis assessed by DAS28-CRP at Week 12.

axSpA Substudy:
To assess the efficacy of SPY072 compared with placebo in reducing the disease activity of axial spondyloarthritis assessed by ASDAS at Week 16.

PsA Substudy:
To assess the efficacy of SPY072 compared with placebo in reducing the disease activity of Psoriatic Arthritis as assessed by ACR20 at Week 16.

Secondary objectives 4

1. RA Substudy: To assess the effect of SPY072 compared with placebo on disease activity as assessed by ACR20 at Week 12. axSpA Substudy: To assess the effect of SPY072 compared with placebo disease activity as assessed by ASAS40 at Week 16. PsA Substudy: To assess the effect of SPY072 compared with placebo disease activity as assessed by DAPSA Week 16.
2. RA Substudy: To assess the PK of SPY072. axSpA Substudy: To assess the PK of SPY072. PsA Substudy: To assess the PK of SPY072.
3. RA Substudy: To assess the immunogenicity of SPY072. axSpA Substudy: To assess the immunogenicity of SPY072. PsA Substudy: To assess the immunogenicity of SPY072.
4. RA Substudy: To assess the safety and tolerability of SPY072. axSpA Substudy: To assess the safety and tolerability of SPY072. PsA Substudy: To assess the safety and tolerability of SPY072.

Conditions and MedDRA coding

Moderately to Severely Active Rheumatologic Disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. RA Substudy: Documented diagnosis of RA and adherence to the meeting the 2010 ACR/European League Against Rheumatism classification criteria for ≥6 months prior to Screening. axSpA Substudy: axSpA for ≥6 months with onset age of <45 years and 1 of the following: a. Meets the modified New York criteria (1984) for axSpA including documented radiologic evidence (X-ray) based on medical records OR b. Meets the 2009 ASAS classification criteria for non-radiographic axSpA (nr-axSpA) with a history of active sacroiliitis on magnetic resonance imaging. c. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, AND Back pain ≥4 (from BASDAI Item 2) at Screening and Day 1. PsA Substudy: Documented diagnosis of adult-onset PsA meeting the Classification Criteria for PsA ≥6 months prior to Screening.
2. RA Substudy: 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. axSpA Substudy: Moderate-to-severely active axSpA defined by BOTH of the following at Screening AND Day 1: a. BASDAI ≥4, AND b. Back pain ≥4 (from BASDAI Item 2). PsA Substudy: Screening and Day 1 tender joint count ≥3 out of 68 and swollen joint count ≥3 out of 66 (dactylitis counts as 1 joint each).
3. RA Substudy: Documentation of ≥1 of the following: a. Positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at Screening, OR b. Radiology report documenting bony erosions in hands or feet consistent with RA on previous radiographs. axSpA Substudy: hsCRP greater than the ULN per the central laboratory at Screening. PsA Substudy: Negative for rheumatoid factor at Screening.
4. RA Substudy: Class I, II, or III of the ACR 1991 Revised Criteria for Global Functional Status in RA. axSpA Substudy: Inadequate response (defined as signs and symptoms of persistently active disease, loss of response, or intolerance) to: a. 2 different NSAIDs given at the maximum tolerated dose for ≥4 weeks or intolerant to or has a contraindication to NSAID therapy; AND/OR b. ≤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). PsA Substudy: ≥1 active plaque psoriasis lesion and/or a documented history of psoriasis.
5. RA Substudy: hsCRP greater than the ULN per the central laboratory at Screening. axSpA Substudy: hsCRP greater than the ULN per the central laboratory at Screening. PsA Substudy: hsCRP greater than the ULN per the central laboratory at Screening.

Exclusion criteria 2

1. RA Substudy: Inadequate response to >2 classes of bDMARDs/tsDMARDs. axSpA Substudy: Inadequate response to >2 classes of bDMARDs/tsDMARDs. PsA Substudy: Inadequate response to >2 classes of bDMARDs/tsDMARDs.
2. RA Substudy: Recent exposure to any of the following: - tsDMARDs within 2 weeks prior to Day 1 or bDMARDs within 4 weeks prior to Day 1 unless drug levels are undetected. - Rituximab within 6 months prior to Day 1 unless B cell counts have recovered in the Investigator’s judgement as per local guidelines. - Cell depleting therapy including but not limited to anti-CD4, anti-CD5, anti-CD3, ocrelizumab, or ofatumumab within 1 year prior to Day 1. - Systemic tacrolimus, azathioprine, parenteral gold, 6-mercaptopurine, 6-thioguanine, cyclosporine, mycophenolate mofetil, immunoadsorption, or D-penicillamine within 4 weeks prior to Day 1, leflunomide within 24 months prior to Day 1 unless the participant has completed cholestyramine elimination treatment and leflunomide levels are undetectable. - Intramuscular, intra-articular, intra-bursal, or intravenous (IV) corticosteroids within 6 weeks prior to Day 1. axSpA Substudy: Recent exposure to any of the following: - tsDMARDs within 2 weeks prior to Day 1 or bDMARDs within 4 weeks prior to Day 1 unless drug levels undetected. - Rituximab within 6 months unless B cell counts have recovered in the Investigator’s judgement as per local guidelines). - Intramuscular, intra-articular, intra-bursal, or IV corticosteroids: within 6 weeks prior to Day 1. PsA Substudy: Exposure to the following: - tsDMARDs within 2 weeks or bDMARDs within 4 weeks prior to Day 1, unless drug levels are undetectable. - Systemic tacrolimus, azathioprine, parenteral gold, 6-mercaptopurine, 6-thioguanine, cyclosporine, mycophenolate mofetil, immunoadsorption, or D-penicillamine within 4 weeks prior to Day 1. - Leflunomide within 24 months unless the participant has completed cholestyramine elimination treatment and leflunomide levels are undetectable. - Intramuscular, intra-articular, intra-bursal, or IV corticosteroids: within 6 weeks prior to Day 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RA Substudy: Change from baseline in DAS28-CRP at Week 12. axSpA Substudy: Change in ASDAS from baseline to Week 16. PsA Substudy: Proportion of participants who achieve an ACR20 response at Week 16.

Secondary endpoints 4

1. RA Substudy: Proportion of participants who achieve an ACR20 response at Week 12. axSpA Substudy: Proportion of participants who achieve an ASAS40 response at Week 16. PsA Substudy: Change in DAPSA from baseline to Week 16.
2. RA Substudy: PK concentration through Week 12. axSpA Substudy: PK concentration through Week 16. PsA Substudy: PK concentration through Week 16.
3. RA Substudy: The proportion of participants with ADA through Week 12. axSpA Substudy: The proportion of participants with ADA through Week 16. PsA Substudy: The proportion of participants with ADA through Week 16.
4. RA Substudy: Incidence of TEAEs, SAEs, AESIs, and AEs leading to IP discontinuation through Week 12 and through the end of study. axSpA Substudy: Incidence of TEAEs, SAEs, AESIs, and AEs leading to IP discontinuation through Week 16 and through the end of study. PsA Substudy: Incidence of TEAEs, SAEs, AESIs, and AEs leading to IP discontinuation at Week 16 and through the end of study.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Spyre Therapeutics Inc.

Sponsor organisation

Spyre Therapeutics Inc.

Address

221 Crescent Street Building 23 Suite 105

City

Waltham

Postcode

02453-3425

Country

United States

Scientific contact point

Organisation

Spyre Therapeutics Inc.

Contact name

SKYWAY-RD Trial Center

Public contact point

Organisation

Spyre Therapeutics Inc.

Contact name

SKYWAY-RD Trial Center

Third parties 13

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 56 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications