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

NCT07012395 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SPY123-201
• Study Type: interventional
• Target: 645
• Locations: 33 countries
• Sites: 222

Brief Summary

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.

Conditions

Ulcerative Colitis; Colitis; Colitis, Ulcerative; Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Week 12

Secondary Outcomes (7)

• Part A: Percentage of participants with clinical remission

  Week 12

• Part A: Percentage of participants with endoscopic improvement

  Week 12

• Part B: Percentage of participants with endoscopic improvement

  Week 12

• Part B: Percentage of participants with clinical response

  Week 12

• Part B: Percentage of participants with histologic improvement

  Week 12

Study Arms (13)

Intervention Specific Appendix - SPY001: Part A

EXPERIMENTAL

Participants will receive open-label dose of SPY001

Drug: SPY001

Intervention Specific Appendix - SPY002: Part A

EXPERIMENTAL

Participants will receive open-label dose of SPY002

Drug: SPY002

Intervention Specific Appendix - SPY003: Part A

EXPERIMENTAL

Participants will receive open-label dose of SPY003

Drug: SPY003

Intervention Specific Appendix - SPY001 Dosing Regimen 1: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 1 of SPY001

Drug: SPY001

Intervention Specific Appendix - SPY001 Dosing Regimen 2: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 2 of SPY001

Drug: SPY001

Intervention Specific Appendix - SPY002 Dosing Regimen 1: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 1 of SPY002

Drug: SPY002

Intervention Specific Appendix - SPY002 Dosing Regimen 2: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 2 of SPY002

Drug: SPY002

Intervention Specific Appendix - SPY003 Dosing Regimen 1: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 1 of SPY003

Drug: SPY003

Intervention Specific Appendix - SPY003 Dosing Regimen 2: Part B

EXPERIMENTAL

Participants will receive double-blind dosing regimen 2 of SPY003

Drug: SPY003

Intervention Specific Appendix - SPY120: Part B

EXPERIMENTAL

Participants will receive double-blind dose of SPY001 and SPY002

Drug: SPY001; Drug: SPY002

Intervention Specific Appendix - SPY130: Part B

EXPERIMENTAL

Participants will receive double-blind dose of SPY001 and SPY003

Drug: SPY001; Drug: SPY003

Intervention Specific Appendix - SPY230: Part B

EXPERIMENTAL

Participants will receive double-blind dose of SPY002 and SPY003

Drug: SPY002; Drug: SPY003

Placebo: Part B

PLACEBO COMPARATOR

Participants will receive matching placebo

Other: Placebo

Interventions

SPY001 DRUG

Experimental

Also known as: SPY001-001

Intervention Specific Appendix - SPY001 Dosing Regimen 1: Part B; Intervention Specific Appendix - SPY001 Dosing Regimen 2: Part B; Intervention Specific Appendix - SPY001: Part A; Intervention Specific Appendix - SPY120: Part B; Intervention Specific Appendix - SPY130: Part B

SPY002 DRUG

Experimental

Also known as: SPY002-091

Intervention Specific Appendix - SPY002 Dosing Regimen 1: Part B; Intervention Specific Appendix - SPY002 Dosing Regimen 2: Part B; Intervention Specific Appendix - SPY002: Part A; Intervention Specific Appendix - SPY120: Part B; Intervention Specific Appendix - SPY230: Part B

SPY003 DRUG

Experimental

Also known as: SPY003-207

Intervention Specific Appendix - SPY003 Dosing Regimen 1: Part B; Intervention Specific Appendix - SPY003 Dosing Regimen 2: Part B; Intervention Specific Appendix - SPY003: Part A; Intervention Specific Appendix - SPY130: Part B; Intervention Specific Appendix - SPY230: Part B

Placebo OTHER

Placebo

Placebo: Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spyre Therapeutics, Inc.: lead

Study Sites (223)

Site 024

Canoga Park, California, 91304, United States

RECRUITING

Site 023

La Jolla, California, 92037, United States

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Site 012

Lancaster, California, 93534, United States

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Site 033

Colorado Springs, Colorado, 91304, United States

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Site 007

Kissimmee, Florida, 34741, United States

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029

Miami, Florida, 33165, United States

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Site 006

Kansas City, Kansas, 66160, United States

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Site 030

Louisville, Kentucky, 40202, United States

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Site 035

Marrero, Louisiana, 70072, United States

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Site 011

Glen Burnie, Maryland, 21061, United States

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Site 003

Boston, Massachusetts, 02114, United States

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Site 028

Rochester, Minnesota, 55905, United States

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Site 037

New York, New York, 10065, United States

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040

Chapel Hill, North Carolina, 27599, United States

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Site 041

Durham, North Carolina, 27710, United States

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Site 016

Winston-Salem, North Carolina, 27103, United States

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Site 025

Providence, Rhode Island, 02904, United States

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Site 017

Kingsport, Tennessee, 37663, United States

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Site 013

Cedar Park, Texas, 78613, United States

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Site 005

Garland, Texas, 75246, United States

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Site 002

San Antonio, Texas, 78229, United States

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Site 008

Southlake, Texas, 76092, United States

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Site 009

Webster, Texas, 77598, United States

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Site 004

Seattle, Washington, 98195, United States

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Site 019

Tacoma, Washington, 98405, United States

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Site 103

Rosario, Sant Fe, 2000, Argentina

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Site 104

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

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Site 208

Concord, 2139, Australia

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Site 202

Heidelberg, 3084, Australia

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Site 204

Liverpool, 2170, Australia

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Site 203

Melbourne, 3004, Australia

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Site 206

South Brisbane, 4101, Australia

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Site 207

Woolloongabba, 4102, Australia

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Site 463

Linz, 4021, Austria

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Site 476

Ghent, Osst-Vlaanderen, 9000, Belgium

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Site 474

Sint-Niklaas, Osst-Vlaanderen, 9100, Belgium

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Site 475

Bruges, 8310, Belgium

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Site 471

Ghent, 9000, Belgium

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Site 472

Roeselare, 9000, Belgium

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Site 481

Banja Luka, 78 000, Bosnia and Herzegovina

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Site 484

Mostar, 88000, Bosnia and Herzegovina

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Site 483

Sarajevo, 71000, Bosnia and Herzegovina

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Site 494

Gorna Oryahovitsa, 5100, Bulgaria

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Site 498

Rousse, 7002, Bulgaria

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Site 492

Sofia, 1343, Bulgaria

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Site 495

Sofia, 1463, Bulgaria

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Site 083

London, Ontario, G8H 3P7, Canada

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Site 085

Greater Sudbury, P3C1X3, Canada

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Site 086

London, N6K 1M6, Canada

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Site 153

Osorno, Los Lagos Region, 5290000, Chile

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Site 521

Osijek, 31000, Croatia

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Site 531

Brno, 615 00, Czechia

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Site 536

Klatovy, 33901, Czechia

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Site 534

Ostrava, 702 00, Czechia

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Site 537

Pardubice, 532 03, Czechia

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Site 538

Prague, 150 00, Czechia

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Site 555

Marseille, 13015, France

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Site 551

Nantes, 44300, France

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Site 557

Nice, 06200, France

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Site 556

Pierre-Bénite, 69310, France

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Site 558

Saint-Etienne, 42270, France

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Site 584

Kutaisi, 4600, Georgia

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Site 589

Marneuli, 3000, Georgia

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Site 581

Tbilisi, 0102, Georgia

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Site 588

Tbilisi, 0114, Georgia

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Site 583

Tbilisi, 01444, Georgia

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Site 586

Tbilisi, 0144, Georgia

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Site 582

Tbilisi, 0159, Georgia

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Site 587

Tbilisi, 0159, Georgia

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Site 590

Tbilisi, 0178, Georgia

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Site 585

Tbilisi, 0180, Georgia

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Site 606

Berlin, 10117, Germany

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Site 604

Berlin, 14163, Germany

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Site 611

Brandenburg an der Havel, 14770, Germany

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Site 607

Dachau, 85221, Germany

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Site 610

Frankfurt am Main, 60590, Germany

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Site 602

Kiel, 24105, Germany

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Site 608

Leipzig, 04103, Germany

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Site 609

Munich, 81377, Germany

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Site 603

Ulm, 89081, Germany

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Site 635

Athens, Attica, 11527, Greece

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Site 634

Athens, 10676, Greece

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Site 632

Athens, 115 27, Greece

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Site 631

Chaïdári, 124 62, Greece

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Site 654

Békéscsaba, H-5600, Hungary

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Site 655

Budapest, H-1062, Hungary

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Site 656

Budapest, H-1083, Hungary

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Site 651

Budapest, H-1088, Hungary

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Site 652

Székesfehérvár, H-8000, Hungary

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Site 270

Hyderabad, 500032, India

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Site 268

Jaipur, 302004, India

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Site 266

Kochi, 682040, India

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Site 265

Sūrat, 395002, India

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Site 445

Beer Yaaqov, 7033001, Israel

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Site 441

Beersheba, 8410101, Israel

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Site 443

Haifa, 31048, Israel

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Site 444

Jerusalem, 9103102, Israel

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Site 446

Jerusalem, 9112001, Israel

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Site 442

Nahariya, 2210001, Israel

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Site 682

Castellana Grotte, Bari, 70013, Italy

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Site 679

Pavia, Lombardy, 27100, Italy

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Site 673

Legnano, Milan, 20025, Italy

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Site 674

Rozzano, Milan, 20089, Italy

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Site 676

San Donato Milanese, Milan, 20097, Italy

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Site 671

Segrate, Milan, 20132, Italy

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Site 680

Turin, Piedmont, 10126, Italy

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Site 683

Bologna, 40138, Italy

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Site 672

Negrar, 37024, Italy

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Site 677

Padova, 35128, Italy

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Site 681

Rome, 00168, Italy

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Site 675

Turin, 10128, Italy

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Site 299

Kashiwa, Chiba, 277-0871, Japan

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Site 294

Chikushino-shi, Fukuoka, 818-8502, Japan

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Site 292

Shiwa-gun, Iwate, 028-3695, Japan

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Site 290

Ōita, Oita Prefecture, 870-0823, Japan

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Site 282

Chuo Ku, Osaka, 540-0006, Japan

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Site 291

Kobe, 650-0015, Japan

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Site 286

Saga, 849-8501, Japan

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Site 285

Sendai, 981-3213, Japan

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Site 293

Urayasu-shi, 279-0021, Japan

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Site 425

Amman, 11194, Jordan

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Site 424

Amman, 11196, Jordan

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Site 421

Amman, 11942, Jordan

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Site 422

Irbid, 21110, Jordan

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Site 423

Irbid, 22110, Jordan

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Site 426

Irbid, 22110, Jordan

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Site 704

Klaipėda, LT-92288, Lithuania

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Site 703

Vilnius, LT-08406, Lithuania

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Site 174

Saltillo, Coahuila, 25050, Mexico

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Site 175

Celaya, Guanajuato, 38000, Mexico

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Site 173

Tlajomulco de Zúñiga, Jalisco, 45645, Mexico

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Site 713

Chisinau, MD2005, Moldova

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Site 711

Chisinau, MD2025, Moldova

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Site 712

Chisinau, MD2025, Moldova

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Site 714

Chisinau, MD2025, Moldova

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Site 715

Chisinau, MD2068, Moldova

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Site 753

Bydgoszcz, 85-2299, Poland

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Site 732

Bydgoszcz, 85-794, Poland

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Site 749

Katowice, 40-600, Poland

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Site 735

Katowice, 40-748, Poland

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Site 748

Krakow, 31-501, Poland

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Site 743

Opole, 45-819, Poland

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Site 740

Poznan, 60-309, Poland

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Site 736

Rzeszów, 35-326, Poland

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Site 744

Sopot, 81-756, Poland

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Site 745

Staszów, 28-2200, Poland

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Site 737

Szczecin, 71-434, Poland

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Site 733

Szczecin, 71-685, Poland

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Site 752

Tychy, 43-100, Poland

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Site 739

Warsaw, 00--710, Poland

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Site 751

Warsaw, 00-189, Poland

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Site 754

Warsaw, 02-172, Poland

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Site 741

Warsaw, 02-786, Poland

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Site 731

Warsaw, 04-501, Poland

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Site 750

Warsaw, 57-300, Poland

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Site 738

Wroclaw, 52-416, Poland

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Site 734

Wroclaw, 53-149, Poland

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Site 747

Wroclaw, 53-611, Poland

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Site 742

Wroclaw, 54-239, Poland

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Site 783

Bucharest, 011273, Romania

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Site 784

Bucharest, 014142, Romania

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Site 781

Bucharest, 020125, Romania

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Site 782

Cluj-Napoca, 400061, Romania

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Site 786

Constanța, 900161, Romania

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Site 788

Timișoara, 300239, Romania

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Trial Site 804

Belgrade, 11 000, Serbia

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Site 802

Belgrade, 11000, Serbia

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Site 807

Belgrade, 11000, Serbia

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Site 803

Belgrade, 11080, Serbia

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Site 805

Niš, 18 000, Serbia

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Site 806

Užice, 31000, Serbia

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Site 801

Zrenjanin, 23000, Serbia

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Site 823

Bratislava, 811 09, Slovakia

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Site 822

Košice, 040 13, Slovakia

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Site 821

Prešov, 080 01, Slovakia

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Site 825

Zvolen, 960 01, Slovakia

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Site 357

Busan, 48108, South Korea

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Site 354

Daegu, 40404, South Korea

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Site 358

Daegu, 42415, South Korea

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Site 361

Daegu, 42601, South Korea

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Site 355

Daejeon, 34943, South Korea

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Site 356

Seoul, 03312, South Korea

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Site 351

Seoul, 03722, South Korea

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Site 352

Seoul, 06591, South Korea

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Site 360

Seoul, 07985, South Korea

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Site 362

Seoul, 6351, South Korea

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Site 359

Suwon, 16247, South Korea

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Site 353

Wŏnju, 26426, South Korea

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Site 832

Santiago de Compostela, A Coruna, 15702, Spain

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Site 835

Gijón, 33394, Spain

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Site 838

Lugo, 27003, Spain

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Site 834

Madrid, 28031, Spain

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Site 837

Madrid, 28222, Spain

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Site 836

Ourense, 32005, Spain

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Site 831

Seville, 41013, Spain

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Site 852

Basel, 4031, Switzerland

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Site 853

Bern, 3012, Switzerland

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Site 851

Sankt Gallen, 9007, Switzerland

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Site 394

Changhua, 500, Taiwan

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Site 392

Chiayi City, 600, Taiwan

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Site 395

Kaohsiung City, 833401, Taiwan

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Site 396

Taichung, 404327, Taiwan

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Site 391

Taipei, 100225, Taiwan

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Site 397

Taipei, 104, Taiwan

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Site 393

Taoyuan City, 333, Taiwan

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Site 866

Kocaeli, 41380, Turkey (Türkiye)

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Site 861

Mersin, 33110, Turkey (Türkiye)

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Site 865

Sanliurfa, 63290, Turkey (Türkiye)

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Site 862

Trabzon, 61080, Turkey (Türkiye)

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Site 906

Ivano-Frankivsk, 76008, Ukraine

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Site 902

Kyiv, 02002, Ukraine

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Site 904

Kyiv, 02091, Ukraine

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Site 905

Kyiv, 03037, Ukraine

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Site 913

Kyiv, 04050, Ukraine

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Site 911

Kyiv, 04107, Ukraine

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Site 903

Kyiv, 04210, Ukraine

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Site 901

Lutsk, 43005, Ukraine

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Site 909

Lviv, 79010, Ukraine

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Site 912

Lviv, 79059, Ukraine

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Site 914

Poltava, 36011, Ukraine

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Site 908

Vinnytsia, 21009, Ukraine

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Site 910

Vinnytsia, 21028, Ukraine

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Site 907

Vinnytsia, 21029, Ukraine

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases; Colitis

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• SKYLINE-UC Study Director

  Spyre Therapeutics

  STUDY DIRECTOR

Central Study Contacts

SKYLINE-UC Trial Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 10, 2025
• Study Start: May 27, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

LI (2); IL (6); BO (3); CH (3); SE (7); MO (5); US (25); TW (7); CA (3); CZ (5); TU (4); RO (6); IN (4); AU (6); GR (4); PL (23); HU (5); SL (4); BU (4); BE (5); JP (9); FR (5); DE (9); UA (14); JO (6); IT (12); KR (12); ES (7); GE (10); AR (2); CL (1); ME (3); CR (1)