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

Phase 2RecruitingNCT07012395

Spyre Therapeutics, Inc.645 enrolled

Overview

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 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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

645

Conditions

Ulcerative Colitis Inflammatory Bowel Diseases Colitis

Interventions

SPY001DRUG

Experimental

SPY002DRUG

Experimental

SPY003DRUG

Experimental

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (223)

Site 024

Canoga Park, California, United States

RECRUITING

Site 023

La Jolla, California, United States

RECRUITING

Site 012

Lancaster, California, United States

RECRUITING

Site 033

Colorado Springs, Colorado, United States

Outcomes

Primary Outcomes

Part A: Change in Robarts Histopathology Index (RHI)

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.

Time frame: Week 12

Part B: Percentage of participants with clinical remission

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.

Time frame: Week 12

Secondary Outcomes

Part A: Percentage of participants with clinical remission

Time frame: Week 12

Part A: Percentage of participants with endoscopic improvement

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.

Time frame: Week 12

Part B: Percentage of participants with endoscopic improvement

Time frame: Week 12

Part B: Percentage of participants with clinical response

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.

Time frame: Week 12

Part B: Percentage of participants with histologic improvement

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.

Time frame: Week 12

Part B: Percentage of participants achieving histologic endoscopic mucosal improvement (HEMI).

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

Time frame: Week 12

Part B: Percentage of participants with clinical remission

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.

Time frame: Week 48

Central Contacts

SKYLINE-UC Trial Center

CONTACT

1-650-402-4238 info@skyline-uc.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Site 007

Kissimmee, Florida, United States

RECRUITING

029

Miami, Florida, United States

RECRUITING

Site 006

Kansas City, Kansas, United States

RECRUITING

Site 030

Louisville, Kentucky, United States

RECRUITING

Site 035

Marrero, Louisiana, United States

RECRUITING

Site 011

Glen Burnie, Maryland, United States

RECRUITING

...and 213 more locations