Long-acting Antibodies for Ulcerative Colitis

(SKYLINE-UC Trial)

Recruiting at 59 trial locations

Overseen By SKYLINE-UC Trial Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Spyre Therapeutics, Inc.

Disqualifiers: Crohn's, Fulminant colitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

645 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new long-acting antibody treatments to determine their effectiveness for people with ulcerative colitis (UC), a condition that inflames the colon and causes symptoms like stomach pain and frequent diarrhea. Researchers aim to assess the safety and effectiveness of these treatments, initially administered by IV and later by injections under the skin. Participants will be divided into groups, each trying different dosing combinations of three treatments: SPY001, SPY002, and SPY003. Individuals who have had UC for at least three months and experience moderate to severe symptoms might be suitable for this study. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found SPY001 to be well-tolerated, with few serious side effects, and it showed a good safety profile. Research suggests that SPY001 has a long duration of action, potentially requiring administration only every three to six months.

SPY002 also showed promise. Early studies indicated that single doses up to 1500 mg were well-tolerated, with most participants experiencing no serious issues. Its safety profile is favorable compared to similar treatments.

SPY003 was well-tolerated as well. Studies demonstrated that it remains in the body for an extended period, allowing for maintenance treatment every three to six months. Its safety profile is comparable to other drugs targeting a specific part of the immune system.

Overall, all three treatments—SPY001, SPY002, and SPY003—were well-tolerated in previous studies. Although this is a Phase 2 trial, these findings provide some reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for ulcerative colitis, which often include aminosalicylates, corticosteroids, and immunosuppressants, SPY001, SPY002, and SPY003 are long-acting antibodies that could offer a new approach to managing the condition. Researchers are excited about these treatments because they have the potential to provide extended relief with less frequent dosing, which could improve patient adherence and quality of life. Additionally, these antibodies might target specific pathways in the immune system, potentially reducing inflammation more effectively and with fewer side effects compared to traditional therapies. This novel mechanism could represent a significant advancement in how ulcerative colitis is treated.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research suggests that SPY001, a treatment in this trial, might work better or faster than current treatments for inflammatory bowel disease. It remains active in the body longer, potentially reducing the number of doses needed. SPY002, another treatment option, targets TL1A, believed to be involved in ulcerative colitis, and earlier studies have shown it to be well tolerated. SPY003, also under investigation, focuses on IL-23, a protein linked to inflammation, and might require dosing only every three to six months. Each treatment has shown promise in early studies, indicating potential effectiveness for treating ulcerative colitis. ^{1 2 4 6 7}

Who Is on the Research Team?

SKYLINE-UC Study Director

Principal Investigator

Spyre Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe ulcerative colitis. Specific details about who can join or reasons why someone might not be allowed to participate are not provided, but typically participants need to meet certain health criteria and cannot have conditions that would interfere with the study.

Inclusion Criteria

My condition is active with a specific severity score and includes bleeding and endoscopic findings.

My ulcerative colitis affects an area at least 15 cm from the anal verge.

I have been diagnosed with ulcerative colitis for over 3 months.

Exclusion Criteria

I have been diagnosed with Crohn's disease or IBD-Undefined.

I have tried 4 or more treatments for my advanced condition without success.

I might need surgery soon due to severe colon issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Open-label Treatment

Participants receive open-label doses of monotherapies to assess safety and preliminary efficacy

12 weeks

Part B: Randomized, Placebo-controlled Treatment

Participants receive randomized, double-blind doses of monotherapies or combination therapies compared to placebo

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SPY001
• SPY002
• SPY003

Trial Overview The study is testing long-acting antibodies named SPY003, SPY001, and SPY002 against a placebo in people with ulcerative colitis. It involves an initial IV treatment followed by maintenance injections under the skin to see if they're safe and effective.

How Is the Trial Designed?

Group I: Intervention Specific Appendix - SPY230: Part B Experimental Treatment 2 Interventions

Participants will receive double-blind dose of SPY002 and SPY003

Group II: Intervention Specific Appendix - SPY130: Part B Experimental Treatment 2 Interventions

Participants will receive double-blind dose of SPY001 and SPY003

Group III: Intervention Specific Appendix - SPY120: Part B Experimental Treatment 2 Interventions

Participants will receive double-blind dose of SPY001 and SPY002

Group IV: Intervention Specific Appendix - SPY003: Part A Experimental Treatment 1 Intervention

Participants will receive open-label dose of SPY003

Group V: Intervention Specific Appendix - SPY003 Dosing Regimen 2: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 2 of SPY003

Group VI: Intervention Specific Appendix - SPY003 Dosing Regimen 1: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 1 of SPY003

Group VII: Intervention Specific Appendix - SPY002: Part A Experimental Treatment 1 Intervention

Participants will receive open-label dose of SPY002

Group VIII: Intervention Specific Appendix - SPY002 Dosing Regimen 2: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 2 of SPY002

Group IX: Intervention Specific Appendix - SPY002 Dosing Regimen 1: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 1 of SPY002

Group X: Intervention Specific Appendix - SPY001: Part A Experimental Treatment 1 Intervention

Participants will receive open-label dose of SPY001

Group XI: Intervention Specific Appendix - SPY001 Dosing Regimen 2: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 2 of SPY001

Group XII: Intervention Specific Appendix - SPY001 Dosing Regimen 1: Part B Experimental Treatment 1 Intervention

Participants will receive double-blind dosing regimen 1 of SPY001

Group XIII: Placebo: Part B Placebo Group 1 Intervention

Participants will receive matching placebo

Who Is Running the Clinical Trial?

Spyre Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

270+

Citations

1. ir.spyre.com ir.spyre.com/news-releases/news-release-details/spyre-therapeutics-announces-poster-presentations-digestive

Release Details "Extended follow-up data continue to show that SPY001 is well tolerated and has a PK and PD profile that supports potential best-in-class quarterly or biannual ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07012395

NCT07012395 | A Study of Long-acting Antibodies Alone ... This is a Phase 2, multicenter, proof-of-concept platform study in adult participants with moderately to severely active ulcerative colitis (UC).

3. sec.gov sec.gov/Archives/edgar/data/1636282/000162828024046860/exhibit991-8xkdatarelease.htm

Spyre Therapeutics Announces Positive Interim Results ... This Phase 2 ulcerative colitis trial is expected to initiate in mid-2025 with SPY001 and placebo arms, with SPY002, SPY003, and combination ...

4. synapse.patsnap.com synapse.patsnap.com/article/spyre-therapeutics-reports-positive-interim-phase-1-results-for-spy001-in-treating-inflammatory-bowel-disease

Spyre Therapeutics Reports Positive Interim Phase 1 ... The data indicate that SPY001 could improve or accelerate efficacy compared to current anti-α4β7 therapies. The findings support potential ...

5. nasdaq.com nasdaq.com/articles/spyre-presents-promising-spy001-ibd-data-and-combination-therapy-results-ddw-2025

Spyre Presents Promising SPY001 IBD Data And ... The updated results show SPY001 continues to be well tolerated, has a half-life more than three times longer than vedolizumab based on ...

6. prnewswire.com prnewswire.com/news-releases/spyre-therapeutics-announces-first-participants-dosed-in-phase-1-trial-of-spy001-its-novel-half-life-extended-anti-47-antibody-for-the-treatment-of-inflammatory-bowel-disease-302174975.html

Spyre Therapeutics Announces First Participants Dosed in ... Preclinical data for SPY001 demonstrate the potential for improved dosing over standard of care, including the potential for dosing every ...

7. academic.oup.com academic.oup.com/ecco-jcc/article-abstract/18/Supplement_1/i1418/7586737

P765 A Novel Monoclonal Antibody Drug Candidate SPY001 ... ... Safety Results From Three Randomized Phase 2 Studies in Crohn's Disease and Ulcerative Colitis · Risk of colectomy is decreasing among newly diagnosed Finnish ...