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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Spyre Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Nov 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Spyre Therapeutics, Inc.

External identifiers

EU CT number

2025-521242-26-00

WHO UTN

U1111-1319-5758

ClinicalTrials.gov

NCT07012395

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Therapy, Pharmacokinetic, Safety, Pharmacodynamic

Part A: To assess the effects of intervention on histologic disease activity following 12 weeks of treatment;
Part B: To assess the efficacy of intervention in inducing clinical remission following 12 weeks of treatment.

Secondary objectives 12

1. Part A: 1. To assess the efficacy of intervention in inducing clinical remission following 12 weeks of treatment.
2. Part A: 2. To assess the efficacy of intervention in inducing endoscopic improvement following 12 weeks of treatment.
3. Part A: 3. To assess the efficacy of intervention in improving clinical disease activity following 12 weeks of treatment.
4. Part A: 4. To evaluate pharmacokinetics of intervention during the Induction Treatment Period (ITP).
5. Part A: 5. To evaluate the presence of anti-drug antibodies (ADA) during the ITP.
6. Part B: 1. To assess the efficacy of intervention in inducing endoscopic improvement following 12 weeks of treatment.
7. Part B: 2. To assess the efficacy of intervention in inducing clinical response following 12 weeks of treatment.
8. Part B: 3. To assess the efficacy of intervention in inducing histologic improvement following 12 weeks of treatment.
9. Part B: 4. To assess the efficacy of intervention in inducing histologic endoscopic mucosal improvement (HEMI) following 12 weeks of treatment.
10. Part B: 5. To assess the efficacy of intervention in achieving clinical remission at the end of the MTP.
11. Part B: 6. To evaluate pharmacokinetics of study drug(s) during the Induction Treatment Period (ITP).
12. Part B: 7. To evaluate the presence of anti-drug antibodies (ADA) during the ITP.

Conditions and MedDRA coding

Moderately to Severely Active Ulcerative Colitis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Male or female ≥18 years of age.
2. 2. Adult participants must have had a diagnosis of UC for ≥3 months before Day 1, confirmed by endoscopy and histology either previously or during Screening.
3. 3. Active UC with disease extent of ≥15 cm from the anal verge, as confirmed by Screening endoscopy, with the exception of up to approximately 15% of the total population permitted to have only proctitis (<15 cm from the anal verge).
4. 4. Moderately to severely active disease as defined by a modified Mayo score of 5 to 9, rectal bleeding subscore of ≥1, and Mayo endoscopic subscore ≥2.
5. 5. History of corticosteroid dependence, OR inadequate response, OR loss of response OR intolerance to 1 of the following: a) conventional therapy only (oral locally acting or systemic corticosteroids, or immunosuppressants) (target of approximately 40%-60% of the planned sample size); OR b) approved advanced therapies, i.e.: anti-TNF, anti-α4β7, anti-IL-12/IL-23, anti-IL-23, JAK inhibitors, or S1P receptor antagonists) (target of approximately 40%-60% of the planned sample size).
6. 6. Participants taking oral corticosteroids (up to 20 mg/day prednisone or equivalent, 9 mg/day budesonide, or 5 mg/day beclomethasone) must be on a stable dose for ≥2 weeks prior to Day 1 and be willing to stay on the same dose during the ITP (for Part A participants), or through Week 6 and initiate taper at Week 6 (for Part B participants).

Exclusion criteria 7

1. 1. Failed (inadequate, lack, or loss of response or intolerance to) 4 or more approved or investigational advanced therapy classes (anti-TNF, anti-α4β7, anti-IL-12/IL-23, anti-IL-23, JAK inhibitors, and S1P receptor antagonists) at the approved labeled dose or higher, if applicable.
2. 2. Failed (inadequate response, loss of response, or intolerance to) 2 or more of the following classes (whether drug is approved or investigational) at an approved labeled dose or higher, if applicable: – anti-α4β7 (e.g., vedolizumab), – anti-TL1A, or – anti-IL-23 (eg, mirikizumab, guselkumab, risankizumab). Note that ustekinumab failure is not applicable to this exclusion criterion.
3. 3. Current diagnosis of Crohn’s disease or IBD-Undefined.
4. 4. History of colectomy (total, subtotal, partial) or ileostomy.
5. 5. If female, pregnant (including those with positive pregnancy test prior to randomization), breastfeeding, or lactating.
6. 6. History and/or current symptoms of infections, including TB, Chronic Hepatitis B or C, COVID-19, HIV, Clostridioides difficile toxin, herpes zoster and Cytomegalovirus.
7. 7. Intervention Specific Appendix-SPY001, Part A Only: Failure (inadequate response, loss of response, or intolerance) of vedolizumab as defined in Master Protocol Appendix 2.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A: Change in RHI from baseline at Week 12.
2. Part B: Clinical remission at Week 12.

Secondary endpoints 12

1. Part A: 1. Clinical remission at Week 12.
2. Part A: 2. Endoscopic improvement at Week 12.
3. Part A: 3. Change in modified Mayo score from baseline at Week 12.
4. Part A: 4. Study drug concentration through Week 12.
5. Part A: 5. Percentage of participants with ADAs to study drug(s) through Week 12.
6. Part B: 1. Endoscopic improvement at Week 12.
7. Part B: 2. Clinical response at Week 12.
8. Part B: 3. Histologic improvement at Week 12.
9. Part B: 4. HEMI at Week 12.
10. Part B: 5. Clinical remission at Week 48.
11. Part B: 6. Study drug concentration through Week 12.
12. Part B: 7. Percentage of participants with ADA to study drug(s) through Week 12.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Spyre Therapeutics Inc.

Sponsor organisation

Spyre Therapeutics Inc.

Address

221 Crescent Street Building 23 Suite 105

City

Waltham

Postcode

02453-3425

Country

United States

Scientific contact point

Organisation

Spyre Therapeutics Inc.

Contact name

SKYLINE-UC Trial Center

Public contact point

Organisation

Spyre Therapeutics Inc.

Contact name

SKYLINE-UC Trial Center

Third parties 14

Locations

16 EU/EEA countries · 124 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 128 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications