A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis
- Conditions
- Ulcerative ColitisInflammatory Bowel DiseasesColitisColitis, Ulcerative
- Interventions
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 645
- 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
- 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.
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Trial Locations
- Locations (11)
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
Site 009
🇺🇸Webster, Texas, United States
Scroll for more (1 remaining)Site 012🇺🇸Lancaster, California, United StatesSKYLINE-UC Trial CenterContact