Colitis · Colitis, Ulcerative · Inflammatory Bowel Diseases · Ulcerative Colitis
Long-Acting Antibodies for Adults With Moderate to Severe Ulcerative Colitis
This Phase 2 study is assessing the efficacy and safety of SPY001, SPY002, and SPY003, alone or in combinations, compared with placebo in adults with moderately to severely active ulcerative colitis.
Registry title: A Study of Long-acting Antibodies Alone and in Combinations for Moderate to Severe Ulcerative Colitis
26 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–75 Years
- Treatment
- SPY001 or SPY002
- Design
- Randomized · Quadruple
- Central study contact
- SKYLINE-UC Trial Center1-650-402-4238info@skyline-uc.com
- Sponsor
- Spyre Therapeutics, Inc.
Research question
How effective and safe are SPY001, SPY002, and SPY003 when given alone or in combinations, including comparison with placebo in Part B, for adults with moderately to severely active ulcerative colitis?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 75.
- The study is looking for people diagnosed with ulcerative colitis at least 3 months before Day 1, confirmed by endoscopy and histology.
- The study is looking for people with active ulcerative colitis extending at least 15 cm from the anal verge; a limited proportion may have only proctitis.
- The study is looking for moderately to severely active disease meeting specified modified Mayo, rectal-bleeding, and endoscopic scores.
Participation overview
What participation may involve
Participants in the enrolling Part B may receive SPY001, SPY002, or SPY003 alone, one of three two-drug combinations, or matching placebo. The study describes intravenous induction followed by subcutaneous maintenance treatment. What participation may involve: - Receive an induction treatment through an intravenous infusion. - Receive maintenance treatment by subcutaneous injection. - Undergo assessments of symptoms and endoscopic disease activity using modified Mayo measures. - Undergo histology assessments of intestinal tissue using measures such as the Robarts Histopathology Index or Geboes score.
Study interventions
What participants may receive or do
- SPY001: An experimental study drug that may be given alone under one of two Part B dosing regimens or combined with SPY002 or SPY003.
- SPY002: An experimental study drug that may be given alone under one of two Part B dosing regimens or combined with SPY001 or SPY003.
- SPY003: An experimental study drug that may be given alone under one of two Part B dosing regimens or combined with SPY001 or SPY002.
- Placebo: A matching placebo used as the comparator in Part B.
Study design
How the comparison works
This Phase 2 platform study has two parts. The completed Part A was open-label and studied the three drugs individually. Part B began enrollment in April 2026 and compares three individual-drug and three combination regimens with placebo. The registry describes Part B as randomized, meaning assignment to its parallel intervention or placebo groups is determined by the study rather than chosen by participants or investigators. Part B uses quadruple masking: participants, care providers, investigators, and outcome assessors are masked to treatment assignment. Part A was open-label. Part B compares six experimental regimens—three single-drug and three combination regimens—with matching placebo. A matching placebo group is included in Part B, but the registry does not report the chance of assignment to placebo.
Reported activities
Procedures and tests
- Screening may include confirming the ulcerative colitis diagnosis by endoscopy and histology if it was not confirmed previously.
- A screening endoscopy is used to confirm how far active ulcerative colitis extends from the anal verge.
- Endoscopic disease activity is assessed using the Mayo endoscopic subscore, with central reading reported for outcome assessments.
- Rectal bleeding and stool frequency are assessed as parts of the modified Mayo score.
- Intestinal tissue histology is assessed using the Robarts Histopathology Index in Part A and Geboes-based measures in Part B.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Ulcerative colitis must have been diagnosed at least 3 months before Day 1 and confirmed by endoscopy and histology, either previously or during screening.
- Active ulcerative colitis must extend at least 15 cm from the anal verge on screening endoscopy; up to approximately 15% of participants may have only proctitis.
- Disease must be moderately to severely active, with a modified Mayo score of 5–9, rectal bleeding subscore of at least 1, and Mayo endoscopic subscore of at least 2.
- Participants must be 18 through 75 years old.
Possible reasons someone may not be able to join
- People with a current diagnosis of Crohn's disease or inflammatory bowel disease–undefined are excluded.
- People with confirmed or suspected fulminant colitis, toxic megacolon, bowel perforation, or another condition likely to require surgery during induction are excluded.
- People who have failed four or more approved or investigational advanced-therapy classes are excluded.
Important unknowns
What the record does not make clear
- The registry does not provide the number, frequency, length, or format of study visits.
- The registry reports outcome assessments at Weeks 12 and 48 but does not state each participant's total time in the study.
- Part B includes a placebo group, but allocation ratios and the chance of receiving placebo are not reported.
- The registry does not explain which current ulcerative colitis treatments may continue during the study.
- No medication washout periods are stated.
- The registry does not describe rescue treatment or what happens if ulcerative colitis worsens.
- The registry identifies screening and outcome-related endoscopic assessments but does not give the complete number, timing, preparation, sedation, or biopsy requirements.
- The registry does not state which study-related or routine-care costs are covered or billed to insurance.
- Compensation or reimbursement is not described.
- The registry does not report whether transportation, lodging, or other travel support is available.
- The registry does not state whether participants can continue an investigational intervention after their assigned study period.
- The study is listed as recruiting and Part B enrollment has begun, but arms may be added or completed at different times, so the available regimens may vary by site.
Before contacting the site
Questions for the study team
- Which Part B intervention or placebo groups are currently open at my preferred site?
- What is the chance of receiving placebo, and how long would the assigned treatment remain blinded?
- What is the complete schedule for screening, infusions, injections, endoscopies, and follow-up visits?
- Which ulcerative colitis medicines may continue, and are any washout periods required?
- How many endoscopies and tissue-sampling procedures are required, and what preparation or sedation is used?
- What happens if ulcerative colitis symptoms worsen during the study?
- Which costs are covered, and is compensation or travel reimbursement available?
Before changing care
Questions for your gastroenterologist
- Would screening or participation require changes to my current ulcerative colitis treatment, and how could those changes affect disease stability?
- How do the study's experimental options compare with approved treatment alternatives that remain appropriate in my clinical situation?
- Are there features of my disease history or current condition that would make intravenous induction, subcutaneous maintenance, or repeated endoscopic assessment especially concerning?
- If I contact the study team, how should you and the research clinicians coordinate medication decisions, monitoring, and care if symptoms worsen?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
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.
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 A enrollment completed April 2026. 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. Part B enrollment commenced April 2026. Intervention arms will be added to the study over time and may complete at different times.
Study design and administration
- Organization
- Spyre Therapeutics, Inc.
- Organization class
- Industry
- Organization study ID
- SPY123-201
- Lead sponsor
- Spyre Therapeutics, Inc.
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Quadruple
- Who is masked
- Participant, Care Provider, Investigator, Outcomes Assessor
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Intervention Specific Appendix - SPY001: Part A
Participants will receive open-label dose of SPY001
Interventions: Drug: SPY001
Experimental
Intervention Specific Appendix - SPY002: Part A
Participants will receive open-label dose of SPY002
Interventions: Drug: SPY002
Experimental
Intervention Specific Appendix - SPY003: Part A
Participants will receive open-label dose of SPY003
Interventions: Drug: SPY003
Experimental
Intervention Specific Appendix - SPY001 Dosing Regimen 1: Part B
Participants will receive double-blind dosing regimen 1 of SPY001
Interventions: Drug: SPY001
Experimental
Intervention Specific Appendix - SPY001 Dosing Regimen 2: Part B
Participants will receive double-blind dosing regimen 2 of SPY001
Interventions: Drug: SPY001
Experimental
Intervention Specific Appendix - SPY002 Dosing Regimen 1: Part B
Participants will receive double-blind dosing regimen 1 of SPY002
Interventions: Drug: SPY002
Experimental
Intervention Specific Appendix - SPY002 Dosing Regimen 2: Part B
Participants will receive double-blind dosing regimen 2 of SPY002
Interventions: Drug: SPY002
Experimental
Intervention Specific Appendix - SPY003 Dosing Regimen 1: Part B
Participants will receive double-blind dosing regimen 1 of SPY003
Interventions: Drug: SPY003
Experimental
Intervention Specific Appendix - SPY003 Dosing Regimen 2: Part B
Participants will receive double-blind dosing regimen 2 of SPY003
Interventions: Drug: SPY003
Experimental
Intervention Specific Appendix - SPY120: Part B
Participants will receive double-blind dose of SPY001 and SPY002
Interventions: Drug: SPY001, Drug: SPY002
Experimental
Intervention Specific Appendix - SPY130: Part B
Participants will receive double-blind dose of SPY001 and SPY003
Interventions: Drug: SPY001, Drug: SPY003
Experimental
Intervention Specific Appendix - SPY230: Part B
Participants will receive double-blind dose of SPY002 and SPY003
Interventions: Drug: SPY002, Drug: SPY003
Placebo Comparator
Placebo: Part B
Participants will receive matching placebo
Interventions: Other: Placebo
Interventions
Drug
SPY001
Experimental
Drug
SPY002
Experimental
Drug
SPY003
Experimental
Other
Placebo
Placebo
Eligibility
18 Years–75 Years
All
Not accepted
Inclusion criteria (3)
- Diagnosis of UC for ≥3 months before Day 1, confirmed by endoscopy and histology either previously or during ScreeningRegistry-derived · unreviewed
- 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)Registry-derived · unreviewed
- Moderately to severely active disease as defined by a modified Mayo score of 5-9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore ≥2Registry-derived · unreviewed
Exclusion criteria (3)
- Current diagnosis of Crohn's disease or Inflammatory Bowel Disease (IBD)-UndefinedRegistry-derived · unreviewed
- Confirmed or suspected fulminant colitis, toxic megacolon, bowel perforation and/or other conditions that will likely require surgery during inductionRegistry-derived · unreviewed
- Failed 4 or more approved or investigational advanced therapy classesRegistry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Part A: Change in Robarts Histopathology Index (RHI)
Time frame: 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.
Primary outcome
Part B: Percentage of participants with clinical remission
Time frame: 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
Part A: Percentage of participants with clinical remission
Time frame: 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
Part A: Percentage of participants with endoscopic improvement
Time frame: 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.
Secondary outcome
Part B: Percentage of participants with endoscopic improvement
Time frame: 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.
Secondary outcome
Part B: Percentage of participants with clinical response
Time frame: 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.
Secondary outcome
Part B: Percentage of participants with histologic improvement
Time frame: 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.
Secondary outcome
Part B: Percentage of participants achieving histologic endoscopic mucosal improvement (HEMI).
Time frame: 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
Secondary outcome
Part B: Percentage of participants with clinical remission
Time frame: 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.
Recruiting locations in the United States
Site 024
RecruitingCanoga Park, California, 91304, United States
SKYLINE-UC Trial Center
Site 023
RecruitingLa Jolla, California, 92037, United States
SKYLINE-UC Trial Center
Site 012
RecruitingLancaster, California, 93534, United States
SKYLINE-UC Trial Center
Site 033
RecruitingColorado Springs, Colorado, 91304, United States
SKYLINE-UC Trial Center
Site 007
RecruitingKissimmee, Florida, 34741, United States
SKYLINE-UC Trial Center
029
RecruitingMiami, Florida, 33165, United States
SKYLINE-UC Trial Center
Site 038
RecruitingChicago, Illinois, 60637, United States
SKYLINE-UC Trial Center
Site 006
RecruitingKansas City, Kansas, 66160, United States
SKYLINE-UC Trial Center
Site 030
RecruitingLouisville, Kentucky, 40202, United States
SKYLINE-UC Trial Center
Site 035
RecruitingMarrero, Louisiana, 70072, United States
SKYLINE-UC Trial Center
Site 011
RecruitingGlen Burnie, Maryland, 21061, United States
Skyline-UC Trial Center
Site 003
RecruitingBoston, Massachusetts, 02114, United States
SKYLINE-UC Trial Center
Site 028
RecruitingRochester, Minnesota, 55905, United States
SKYLINE-UC Trial Center
Site 037
RecruitingNew York, New York, 10065, United States
SKYLINE-UC Trial Center
040
RecruitingChapel Hill, North Carolina, 27599, United States
SKYLINE-UC Trial Center
Site 041
RecruitingDurham, North Carolina, 27710, United States
SKYLINE-UC Trial Center
Site 016
RecruitingWinston-Salem, North Carolina, 27103, United States
SKYLINE-UC Trial Center
Site 025
RecruitingProvidence, Rhode Island, 02904, United States
SKYLINE- UC Trial Center
Site 017
RecruitingKingsport, Tennessee, 37663, United States
SKYLINE-UC Trial Center
Site 013
RecruitingCedar Park, Texas, 78613, United States
SKYLINE-UC Trial Center
Site 005
RecruitingGarland, Texas, 75246, United States
SKYLINE-UC Trial Center
Site 002
RecruitingSan Antonio, Texas, 78229, United States
SKYLINE-UC Trial Center
Site 008
RecruitingSouthlake, Texas, 76092, United States
SKYLINE-UC Trial Center
Site 009
RecruitingWebster, Texas, 77598, United States
SKYLINE-UC Trial Center
Site 004
RecruitingSeattle, Washington, 98195, United States
SKYLINE-UC Trial Center
Site 019
RecruitingTacoma, Washington, 98405, United States
SKYLINE-UC Trial Center
This study also lists 233 locations outside the United States. They are not shown here.
Central study contacts
Registry dates
- First posted
- Jun 10, 2025
- Primary completion
- Jun 2027
- Overall completion
- Mar 2028
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.