A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis

Phase 2

Recruiting

• Conditions: Ulcerative Colitis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Interventions: Drug: SPY003; Drug: SPY001; Drug: SPY002; Other: Placebo

• Registration Number: NCT07012395
• Lead Sponsor: Spyre Therapeutics, Inc.

Brief Summary

This is a Phase 2, multicenter, proof-of-concept platform study in adult participants with moderately to severely active ulcerative colitis (UC). The primary goal of the study is to assess the efficacy and safety of multiple interventions following intravenous (IV) induction and subcutaneous (SC) maintenance treatment.

Detailed Description

This platform study will evaluate the efficacy and safety of investigational treatments, including 3 monotherapies and 3 combination therapies, for moderately to severely active UC in adults. The study will progress in two parts.

Part A is the open-label portion of the study assessing safety and preliminary efficacy of monotherapies.

Part B, which will be open for enrollment after Part A, is the randomized, placebo-controlled portion of the study assessing the safety and efficacy of the 6 interventions (3 monotherapies and 3 combinations) compared to placebo.

Intervention arms will be added to the study over time and may complete at different times.

Study Timeline

• Study Start: 2025-05-27
• Study First Submitted: 2025-05-27
• Study First Submitted QC: 2025-06-04
• Study First Posted: 2025-06-10
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-15
• Last Update Posted: 2025-07-16
• Primary Completion: 2026-06
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 645

Inclusion Criteria

• Diagnosis of UC for ≥3 months before Day 1, confirmed by endoscopy and histology either previously or during Screening
• Active UC with disease extent of ≥15 cm from the anal verge, as confirmed by Screening endoscopy (up to approximately 15% allowed to have only proctitis)
• Moderately to severely active disease as defined by a modified Mayo score of 5-9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore ≥2

Exclusion Criteria

• Current diagnosis of Crohn's disease or Inflammatory Bowel Disease (IBD)-Undefined
• Confirmed or suspected fulminant colitis, toxic megacolon, bowel perforation and/or other conditions that will likely require surgery during induction
• Failed 4 or more approved or investigational advanced therapy classes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Specific Appendix - SPY003: Part A	SPY003	Participants will receive open-label dose of SPY003
Intervention Specific Appendix - SPY001 Dosing Regimen 1: Part B	SPY001	Participants will receive double-blind dosing regimen 1 of SPY001
Intervention Specific Appendix - SPY001 Dosing Regimen 2: Part B	SPY001	Participants will receive double-blind dosing regimen 2 of SPY001
Intervention Specific Appendix - SPY002 Dosing Regimen 1: Part B	SPY002	Participants will receive double-blind dosing regimen 1 of SPY002
Intervention Specific Appendix - SPY002 Dosing Regimen 2: Part B	SPY002	Participants will receive double-blind dosing regimen 2 of SPY002
Intervention Specific Appendix - SPY003 Dosing Regimen 1: Part B	SPY003	Participants will receive double-blind dosing regimen 1 of SPY003
Intervention Specific Appendix - SPY003 Dosing Regimen 2: Part B	SPY003	Participants will receive double-blind dosing regimen 2 of SPY003
Intervention Specific Appendix - SPY120: Part B	SPY001	Participants will receive double-blind dose of SPY001 and SPY002
Intervention Specific Appendix - SPY120: Part B	SPY002	Participants will receive double-blind dose of SPY001 and SPY002
Intervention Specific Appendix - SPY130: Part B	SPY001	Participants will receive double-blind dose of SPY001 and SPY003
Intervention Specific Appendix - SPY130: Part B	SPY003	Participants will receive double-blind dose of SPY001 and SPY003
Intervention Specific Appendix - SPY230: Part B	SPY002	Participants will receive double-blind dose of SPY002 and SPY003
Intervention Specific Appendix - SPY230: Part B	SPY003	Participants will receive double-blind dose of SPY002 and SPY003
Placebo: Part B	Placebo	Participants will receive matching placebo
Intervention Specific Appendix - SPY002: Part A	SPY002	Participants will receive open-label dose of SPY002
Intervention Specific Appendix - SPY001: Part A	SPY001	Participants will receive open-label dose of SPY001

Primary Outcome Measures

Name	Time	Method
Part A: Change in Robarts Histopathology Index (RHI)	Week 12	Change in Robarts Histopathology Index (RHI) from baseline at Week 12 will be assessed. The RHI is used to quantify and assess histological activity of UC, comprising of scores for inflammatory infiltrates, neutrophils, erosions or ulceration. Scores are assigned to each of these features, with a total ranging from 0 (no disease activity) to 33 (most severe disease activity). Higher score indicates more severe disease.
Part B: Percentage of participants with clinical remission	Week 12	Percentage of participants with clinical remission at Week 12 will be assessed. Clinical remission is based on the modified Mayo subscores, which consist of a rectal bleeding subscore (ranging from 0 to 3), stool frequency subscore (ranging from 0 to 3), and endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher scores indicate more severe disease.

Secondary Outcome Measures

Name	Time	Method
Part B: Percentage of participants achieving histologic endoscopic mucosal improvement (HEMI).	Week 12	Percentage of participants with HEMI at Week 12 will be assessed. Mucosal improvement is based on the Mayo endoscopic subscore and the Geboes score. The Mayo endoscopic subscore ranges from 0 to 3, as assessed by central reading. Higher score indicates more severe disease. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. Higher score indicates more severe disease
Part B: Percentage of participants with clinical remission	Week 48	Percentage of participants with clinical remission at Week 48 will be assessed. Clinical remission is based on the modified Mayo subscores, which consist of a rectal bleeding subscore (ranging from 0 to 3), stool frequency subscore (ranging from 0 to 3), and endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher scores indicate more severe disease.
Part A: Percentage of participants with clinical remission	Week 12	Percentage of participants with clinical remission at Week 12 will be assessed. Clinical remission is based on the modified Mayo subscores, which consist of a rectal bleeding subscore (ranging from 0 to 3), stool frequency subscore (ranging from 0 to 3), and endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher scores indicate more severe disease.
Part A: Percentage of participants with endoscopic improvement	Week 12	Percentage of participants with endoscopic improvement at Week 12 will be assessed. Endoscopic improvement based on the Mayo endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher score indicates more severe disease.
Part B: Percentage of participants with endoscopic improvement	Week 12	Percentage of participants with endoscopic improvement at Week 12 will be assessed. Endoscopic improvement based on the Mayo endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher score indicates more severe disease.
Part B: Percentage of participants with clinical response	Week 12	Percentage of participants with clinical response at Week 12 will be assessed. Clinical response is based on the modified Mayo Score, which consist of a rectal bleeding subscore (ranging from 0 to 3), stool frequency subscore (ranging from 0 to 3), and endoscopic subscore (ranging from 0 to 3), as assessed by central reading. Higher scores indicate more severe disease.
Part B: Percentage of participants with histologic improvement	Week 12	Percentage of participants with histologic improvement at Week 12 will be assessed. Histologic improvement is based on the Geboes score. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. Higher score indicates more severe disease.

Trial Locations

Locations (11)

Site 019; 🇺🇸 Tacoma, Washington, United States

Site 012; 🇺🇸 Lancaster, California, United States

Site 007; 🇺🇸 Kissimmee, Florida, United States

Site 016; 🇺🇸 Winston-Salem, North Carolina, United States

Site 025; 🇺🇸 Providence, Rhode Island, United States

Site 017; 🇺🇸 Kingsport, Tennessee, United States

Site 013; 🇺🇸 Cedar Park, Texas, United States

Site 005; 🇺🇸 Garland, Texas, United States

Site 002; 🇺🇸 San Antonio, Texas, United States

Site 008; 🇺🇸 Southlake, Texas, United States

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