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NCT Number: NCT07012395

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

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.

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Key information

Conditions

Ulcerative Colitis Colitis Colitis, Ulcerative Colonic Diseases Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Site 105, La Plata, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

SPY001

Drug

Experimental

Other names: SPY001-001

SPY002

Drug

Experimental

Other names: SPY002-091

SPY003

Drug

Experimental

Other names: SPY003-207

Placebo

Other

Placebo

Primary outcomes

  1. 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.

  2. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

SKYLINE-UC Trial Center

CONTACT

[email protected]

1-650-402-4238

Sponsors and collaborators

Lead sponsor

Spyre Therapeutics, Inc.

Industry

Registry information

Official study title

Phase 2 Platform Trial to Assess the Efficacy and Safety of Long-acting Antibodies as Single Agents and in Combinations for Moderately to Severely Active Ulcerative Colitis

Acronym: SKYLINE-UC

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jun 10, 2025
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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