A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)

NCT04677179 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: 17287J1P-MC-KFAH2020-003017-35
• Study Type: interventional
• Target: 81
• Locations: 22 countries
• Sites: 116

Brief Summary

The reason for this study is to determine if the study drug LY3471851 is safe and effective in adult participants with active ulcerative colitis (UC). The study treatment will last about 52 weeks.

Conditions

Colitis, Ulcerative

Keywords

T regulatory cells (Tregs); Interleukin 2; Interleukin-2

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Clinical Remission at Week 12

  Clinical remission is defined as achieving a Modified Mayo Score (MMS) sub-score for rectal bleeding=0, stool frequency=0, or stool frequency=1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability). The MMS is a scoring system for assessment of UC and is composed of sub-scores of stool frequency (range: 0 to 3, where 0=normal number of stools, 3=5 or more stools more than normal), endoscopy (range: 0 to 3, where 0=normal or inactive disease, 3=severe disease \[spontaneous bleeding, ulceration\]), rectal bleeding (range: 0 to 3, where 0=no blood seen, 3=blood alone passed). Total MMS score is sum of all sub-scores and ranges from 0 to 9, with higher scores indicating higher disease activity.

  Week 12

Secondary Outcomes (9)

• Percentage of Participants Who Achieved Clinical Response at Week 12

  Week 12

• Percentage of Participants Who Achieved Endoscopic Remission at Week 12

  Week 12

• Percentage of Participants Who Achieved Endoscopic Response at Week 12

  Week 12

• Percentage of Participants Who Achieved Symptomatic Remission at Week 12

  Week 12

• Percentage of Participants Who Achieved Symptomatic Response at Week 12

  Week 12

Study Arms (3)

High dose LY3471851

EXPERIMENTAL

Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Drug: LY3471851

Low dose LY3471851

EXPERIMENTAL

Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Drug: LY3471851

Placebo

PLACEBO COMPARATOR

Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.

Drug: LY3471851; Drug: Placebo

Interventions

LY3471851 DRUG

administered SC

Also known as: NKTR-358

High dose LY3471851; Low dose LY3471851; Placebo

Placebo DRUG

administered SC

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have moderately to severely active ulcerative colitis (UC) as defined by a modified Mayo score (MMS) of 4 to 9 with an endoscopic subscore (ES) ≥2, with endoscopy performed within 14 days before baseline.
• Have evidence of UC extending proximal to the rectum (with ≥15 centimeters (cm) of involved colon).
• Have up-to-date colorectal cancer surveillance performed according to local standard.
• Participants are either one of the following:
• Have failed conventional treatments including inability to tolerate oral or intravenous corticosteroids or immunomodulators (6-mercaptopurine or azathioprine or methotrexate), or history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC) and neither failed or demonstrated intolerance to advanced therapy (eg, tumor necrosis factor (TNF) antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase (JAK) inhibitor) OR,
• Have failed advanced therapies such as treatment with 1 or more advance therapies (eg, tumor necrosis factor \[TNF\] antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase \[JAK\] inhibitor) at doses approved for the treatment of UC with documented history of failure to respond to or tolerate such treatment.
• Have had an established diagnosis of UC of ≥3 months in duration before baseline which includes endoscopic evidence of UC and a histopathology report that supports a diagnosis of UC. Supportive endoscopy and histopathology reports must be available in the source documents.
• Women of child-bearing potential (WOCBP) must test negative for pregnancy as indicated by a negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test within 24 hours prior to first exposure to study drug.

You may not qualify if:

• Have been diagnosed with indeterminant colitis, proctitis (colitis limited to the rectum only; less than 15 centimeter (cm) from the anal verge or Crohn's disease.
• Have received any of the following for treatment of UC: cyclosporine, tacrolimus, mycophenolate mofetil or thalidomide within 2 weeks of screening, rectally administered corticosteroids or 5-aminosalicylic acid treatments within 2 weeks of screening.
• Have had or will need abdominal surgery for UC (for example, subtotal colectomy).
• Have failed 3 or more classes of advanced therapies approved for treatment of UC (eg, tumor necrosis factor \[TNF\] antagonists, anti-integrin therapies, anti-IL12/23p40 therapies, Janus kinase \[JAK\] inhibitor).
• Have evidence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis within the small bowel or colon.
• Have any history or evidence of cancer of the gastrointestinal tract
• Have myocardial infarction, unstable ischemic heart disease, stroke or heart failure within 12 months prior to screening.

Sponsors & Collaborators

• Nektar Therapeutics: lead
• Eli Lilly and Company: collaborator

Study Sites (116)

Dedicated Clinical Research

Litchfield Park, Arizona, 85340, United States

Location

I.H.S. Health, LLC

Kissimmee, Florida, 34741, United States

Location

Gastroenterology Associates of Pensacola, PA

Pensacola, Florida, 32503, United States

Location

Atlantic Digestive Health Institute

Morristown, New Jersey, 07960, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77084, United States

Location

Southern Star Research Institute, LLC

San Antonio, Texas, 78229, United States

Location

Care Access Research - Ogden

Ogden, Utah, 84403, United States

Location

DOM- Centro de Reumatologia

CABA, Buenos Aires, 1111, Argentina

Location

Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC

CABA, Buenos Aires, C1431FWO, Argentina

Location

Mautalen Salud e Investigacion-Centro de Osteopatías Médicas

Ciudad Autonoma de Buenos Air, Buenos Aires, C1128AAF, Argentina

Location

Centro Médico Privado de Reumatología

San Miguel de Tucumán, T4000AXL, Argentina

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Paratus Clinical Research Brisbane

Albion, Queensland, 4010, Australia

Location

Mater Adult Hospital Brisbane

South Brisbane, Queensland, 4700, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Université Libre de Bruxelles - Hôpital Erasme

Brussels, Bruxelles-Capitale, Région de, 1070, Belgium

Location

Centre Hospitalier de Wallonie Picarde - Site Notre Dame

Tournai, Wallonne, Région, 7500, Belgium

Location

AZ Maria Middelares

Ghent, 9100, Belgium

Location

Chronos Pesquisa Clínica

Brasília, Federal District, 72145-450, Brazil

Location

Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP

Botucatu, São Paulo, 18618-687, Brazil

Location

HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas

Campinas, São Paulo, 13060-904, Brazil

Location

Pesquisare

Santo André, São Paulo, 09080-110, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Instituto de Assistencia Medica ao Servidor Publico Estudo Estadual

São Paulo, São Paulo, 04039-004, Brazil

Location

Hepatogastro

São Paulo, 04543-001, Brazil

Location

Gastroenterology and internal medicine research institute

Edmonton, Alberta, T5R 1W2, Canada

Location

Gastroenterology Research, Nova Scotia Health Authority

Halifax, Nova Scotia, B3H2Y9, Canada

Location

CISSS de la Montérégie - Centre Hôpital Charles-Le Moyne

Greenfield Park, Quebec, J4V2H1, Canada

Location

McGill University

Montreal, Quebec, H3G 1A4, Canada

Location

The First Affiliated Hospital of Anhui Medical University

HefeiCity, Anhui, 230022, China

Location

First affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510080, China

Location

The Sixth Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510655, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech

Wuhan, Hubei, 430030, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Taian City Central Hospital

Taian, Shandong, 271000, China

Location

Shanghai Jiaotong University School of Medicine Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, 310018, China

Location

A-Shine

Pilsen, Plzeň-město, 312 00, Czechia

Location

MUDr. Gregar, s.r.o.

Olomouc, 779 00, Czechia

Location

PreventaMed, s.r.o.

Olomouc, 779 00, Czechia

Location

I. Interni klinika FN Plzen

Plzen-Lochotin, 304 60, Czechia

Location

Nemocnice Slaný

Slaný, 274 01, Czechia

Location

CHU De Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

Centre Hospitalier de Mont de Marsan

Mont-de-Marsan, 40024, France

Location

Acad. F. Todua Medical Center - Research Institute of Clinical Medicine

Tbilisi, 0112, Georgia

Location

Medical Center: Medinvestment

Tbilisi, 0186, Georgia

Location

Clinexpert SMO

Budapest, 1033, Hungary

Location

Óbudai Egészségügyi Centrum

Budapest, 1036, Hungary

Location

Bugát Pál Kórház

Gyöngyös, 3200, Hungary

Location

CLINFAN Szolgáltató Kft

Szekszárd, 7100, Hungary

Location

Shree Giriraj Multispeciality Hospital

Rajkot, Gujarat, 360004, India

Location

Gujarat Hospital - Gastro and Vascular Centre

Surat, Gujarat, 395009, India

Location

Kingsway Hospital

Nagpur, Maharashtra, 440001, India

Location

Midas Multispeciality Hospital Pvt.Ltd.

Nagpur, Maharashtra, 440010, India

Location

SR Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, 302006, India

Location

Apollo Speciality Hospital - Teynampet

Chennai, Tamil Nadu, 600035, India

Location

Postgraduate Institute of Medical Education & Research

Chandigarh, 160012, India

Location

Gandhi Hospital

Telangana, 500003, India

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Galilee Medical Center - Internal A

Nahariya, 22100, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

Fukuoka University Chikushi Hospital

Chikushino-shi, Fukuoka, Japan

Location

Tokushukai Sapporo Tokushukai Hospital

Sapporo, Hokkaido, 004 0041, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Location

Sai Gastroenterologist Proctology

Fujiidera, Osaka, 583-0027, Japan

Location

Infusion Clinic

Osaka, Osaka, 530-0011, Japan

Location

Matsuda Hospital

Hamamatsu, Shizuoka, 4328061, Japan

Location

Showa University Koto Toyosu Hospital

Koto-ku, Tokyo, 135 8577, Japan

Location

Kyorin University Hospital

Mitaka, Tokyo, 181-8611, Japan

Location

Center Hospital of the National Center for Global Health and Medicine

Shinjuku-ku, Tokyo-To, 162 8655, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Sameshima Hospital

Kagoshima, 892-0846, Japan

Location

Toyama Prefectural Central Hospital

Toyama, 930-8550, Japan

Location

Yamagata University Hospital

Yamagata, 990-9585, Japan

Location

Pauls Stradins Clinical Univeristy Hospital

Riga, Rīga, LV-1002, Latvia

Location

NZOZ Vivamed

Warsaw, Masovian Voivodeship, 03-580, Poland

Location

Szpital Miejski Sw. Jana Pawla II

Elblag, 82-300, Poland

Location

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, 00-728, Poland

Location

ETG Zamość

Zamość, 22-400, Poland

Location

SC Pelican SRL

Oradea, Bihor County, 410469, Romania

Location

SC Med Life SA

Bucharest, 010719, Romania

Location

SC Centrul Medical Sana SRL

Bucharest, 011025, Romania

Location

Spital Clinic Colentina

Bucharest, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, 400006, Romania

Location

S.C. Materna Care S.R.L.

Timișoara, 300645, Romania

Location

Olla-Med

Moscow, Moscow, 105554, Russia

Location

Novosibirski Gastrocenter

Novosibirsk, Novosibirsk Oblast, 630007, Russia

Location

Rostov State Medical University

Rostov-on-Don, Rostov Oblast, 344091, Russia

Location

Open Joint Stock Company Clinical and Diagnostic Center Euromedservice

Moscow, Russia

Location

The University Clinic of OSMU

Omsk, 644050, Russia

Location

SPb SBIH "City Mariinskaya Hospital"

Saint Petersburg, 194104, Russia

Location

GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen of Health

Saint Petersburg, 195067, Russia

Location

FNsP FDRoosevelta Banska Bystrica

Banská Bystrica, 97517, Slovakia

Location

ENDOMED s.r.o.

Košice, 04013, Slovakia

Location

Yonsei University Wonju Severance Christian Hospital

Gangwon-do, Gangwon-do, 26426, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 443380, South Korea

Location

Samsung Medical Center

Seoul, Korea, 06351, South Korea

Location

Seoul St. Mary's Hospital

Seoul, Korea, 06591, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Medical Center of Limited Liability Company "Medical Center "Consilium Medical"

Kiev, Kyiv Oblast, 4050, Ukraine

Location

Lviv Railway Clinical Hospital

Lviv, Lviv Oblast, 79000, Ukraine

Location

Lviv Regional Endocrinology Dispensary

Lviv, Lviv Oblast, 79000, Ukraine

Location

Medical Center of LLC Medical Center Clinic of Family Medicine

Dnipro, Ukraine

Location

International Institute of Clinical Trials LLC

Kyiv, 02091, Ukraine

Location

Communal Enterprise "Odesa Regional Clinical Hospital"

Odesa, 65000, Ukraine

Location

A. Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, 88018, Ukraine

Location

CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM

Vinnytsia, 21029, Ukraine

Location

Vinnytsia War Veterans Regional Clinical Hospital

Vinnytsia, Ukraine

Location

Diacenter LLC

Zaporizhzhia, 69076, Ukraine

Location

Royal Derby Hospital

Derby, Derbyshire, DE22 3NE, United Kingdom

Location

Whipps Cross University Hospital

Leytonstone, London, E11 1NR, United Kingdom

Location

Guys/St. Thomas Hospital

London, Surrey, SE1 9RT, United Kingdom

Location

St. George's Hospital

London, SW17 0QT, United Kingdom

Location

York Hospital

York, YO31 8HE, United Kingdom

Location

Related Links

• A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC) ( INSTRUCT-UC )

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Nektar Therapeutics

StudyInquiry@nektar.com

855-482-8676

Study Officials

• Study Director

  Nektar Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 21, 2020
• Study Start: March 22, 2021
• Primary Completion: August 9, 2022
• Study Completion: August 9, 2022
• Last Updated: September 5, 2023
• Results First Posted: September 5, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (5); GE (2); RO (6); RU (7); JP (13); US (7); GB (5); LA (1); BE (3); HU (4); AR (4); BR (8); AU (4); CA (4); FR (2); IL (3); PL (4); SL (2); IN (8); KR (5); UA (10); CN (9)