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

NCT ID: NCT04677179

Last Updated: 2023-09-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-22
• Study Completion Date: 2022-08-09

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.

Detailed Description

In stage 1, two doses (high and low) of LY3471851 will be compared to placebo. In stage 2, up to two additional doses (to be confirmed) of LY3471851 will be compared to placebo.

LY3471851 (NKTR-358) is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.

Conditions

Colitis, Ulcerative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

High dose LY3471851

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.

Group Type: EXPERIMENTAL

LY3471851

Intervention Type: DRUG

administered SC

Low dose LY3471851

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.

Group Type: EXPERIMENTAL

LY3471851

Intervention Type: DRUG

administered SC

Placebo

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.

Group Type: PLACEBO_COMPARATOR

LY3471851

Intervention Type: DRUG

administered SC

Placebo

Intervention Type: DRUG

administered SC

Interventions

LY3471851

administered SC

Intervention Type: DRUG

Placebo

administered SC

Intervention Type: DRUG

Other Intervention Names

NKTR-358

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Nektar Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Nektar Therapeutics

Locations

Dedicated Clinical Research

Litchfield Park, Arizona, United States

I.H.S. Health, LLC

Kissimmee, Florida, United States

Gastroenterology Associates of Pensacola, PA

Pensacola, Florida, United States

Atlantic Digestive Health Institute

Morristown, New Jersey, United States

Biopharma Informatic, LLC

Houston, Texas, United States

Southern Star Research Institute, LLC

San Antonio, Texas, United States

Care Access Research - Ogden

Ogden, Utah, United States

DOM- Centro de Reumatologia

CABA, Buenos Aires, Argentina

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

CABA, Buenos Aires, Argentina

Mautalen Salud e Investigacion-Centro de Osteopatías Médicas

Ciudad Autonoma de Buenos Air, Buenos Aires, Argentina

Centro Médico Privado de Reumatología

San Miguel de Tucumán, , Argentina

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Paratus Clinical Research Brisbane

Albion, Queensland, Australia

Mater Adult Hospital Brisbane

South Brisbane, Queensland, Australia

St. Vincent's Hospital

Fitzroy, Victoria, Australia

Université Libre de Bruxelles - Hôpital Erasme

Brussels, Bruxelles-Capitale, Région de, Belgium

Centre Hospitalier de Wallonie Picarde - Site Notre Dame

Tournai, Wallonne, Région, Belgium

AZ Maria Middelares

Ghent, , Belgium

Chronos Pesquisa Clínica

Brasília, Federal District, Brazil

Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS

Porto Alegre, Rio Grande do Sul, Brazil

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

Botucatu, São Paulo, Brazil

HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas

Campinas, São Paulo, Brazil

Pesquisare

Santo André, São Paulo, Brazil

CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda

São Bernardo do Campo, São Paulo, Brazil

Instituto de Assistencia Medica ao Servidor Publico Estudo Estadual

São Paulo, São Paulo, Brazil

Hepatogastro

São Paulo, , Brazil

Gastroenterology and internal medicine research institute

Edmonton, Alberta, Canada

Gastroenterology Research, Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

CISSS de la Montérégie - Centre Hôpital Charles-Le Moyne

Greenfield Park, Quebec, Canada

McGill University

Montreal, Quebec, Canada

The First Affiliated Hospital of Anhui Medical University

HefeiCity, Anhui, China

First affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

The Sixth Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China

Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech

Wuhan, Hubei, China

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Taian City Central Hospital

Taian, Shandong, China

Shanghai Jiaotong University School of Medicine Ruijin Hospital

Shanghai, Shanghai Municipality, China

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, China

A-Shine

Pilsen, Plzeň-město, Czechia

MUDr. Gregar, s.r.o.

Olomouc, , Czechia

PreventaMed, s.r.o.

Olomouc, , Czechia

I. Interni klinika FN Plzen

Plzen-Lochotin, , Czechia

Nemocnice Slaný

Slaný, , Czechia

CHU De Grenoble Hopital Albert Michallon

Grenoble, , France

Centre Hospitalier de Mont de Marsan

Mont-de-Marsan, , France

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

Tbilisi, , Georgia

Medical Center: Medinvestment

Tbilisi, , Georgia

Clinexpert SMO

Budapest, , Hungary

Óbudai Egészségügyi Centrum

Budapest, , Hungary

Bugát Pál Kórház

Gyöngyös, , Hungary

CLINFAN Szolgáltató Kft

Szekszárd, , Hungary

Shree Giriraj Multispeciality Hospital

Rajkot, Gujarat, India

Gujarat Hospital - Gastro and Vascular Centre

Surat, Gujarat, India

Kingsway Hospital

Nagpur, Maharashtra, India

Midas Multispeciality Hospital Pvt.Ltd.

Nagpur, Maharashtra, India

SR Kalla Memorial Gastro & General Hospital

Jaipur, Rajasthan, India

Apollo Speciality Hospital - Teynampet

Chennai, Tamil Nadu, India

Postgraduate Institute of Medical Education & Research

Chandigarh, , India

Gandhi Hospital

Telangana, , India

Soroka Medical Center

Beersheba, , Israel

Galilee Medical Center - Internal A

Nahariya, , Israel

Kaplan Medical Center

Rehovot, , Israel

Fukuoka University Chikushi Hospital

Chikushino-shi, Fukuoka, Japan

Tokushukai Sapporo Tokushukai Hospital

Sapporo, Hokkaido, Japan

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Sai Gastroenterologist Proctology

Fujiidera, Osaka, Japan

Infusion Clinic

Osaka, Osaka, Japan

Matsuda Hospital

Hamamatsu, Shizuoka, Japan

Showa University Koto Toyosu Hospital

Koto-ku, Tokyo, Japan

Kyorin University Hospital

Mitaka, Tokyo, Japan

Center Hospital of the National Center for Global Health and Medicine

Shinjuku-ku, Tokyo-To, Japan

Fukuoka University Hospital

Fukuoka, , Japan

Sameshima Hospital

Kagoshima, , Japan

Toyama Prefectural Central Hospital

Toyama, , Japan

Yamagata University Hospital

Yamagata, , Japan

Pauls Stradins Clinical Univeristy Hospital

Riga, Rīga, Latvia

NZOZ Vivamed

Warsaw, Masovian Voivodeship, Poland

Szpital Miejski Sw. Jana Pawla II

Elblag, , Poland

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, , Poland

ETG Zamość

Zamość, , Poland

SC Pelican SRL

Oradea, Bihor County, Romania

SC Med Life SA

Bucharest, , Romania

SC Centrul Medical Sana SRL

Bucharest, , Romania

Spital Clinic Colentina

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, , Romania

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

Timișoara, , Romania

Olla-Med

Moscow, Moscow, Russia

Novosibirski Gastrocenter

Novosibirsk, Novosibirsk Oblast, Russia

Rostov State Medical University

Rostov-on-Don, Rostov Oblast, Russia

Open Joint Stock Company Clinical and Diagnostic Center Euromedservice

Moscow, , Russia

The University Clinic of OSMU

Omsk, , Russia

SPb SBIH "City Mariinskaya Hospital"

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

FNsP FDRoosevelta Banska Bystrica

Banská Bystrica, , Slovakia

ENDOMED s.r.o.

Košice, , Slovakia

Yonsei University Wonju Severance Christian Hospital

Gangwon-do, Gangwon-do, South Korea

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Samsung Medical Center

Seoul, Korea, South Korea

Seoul St. Mary's Hospital

Seoul, Korea, South Korea

Inje University Haeundae Paik Hospital

Busan, , South Korea

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

Kiev, Kyiv Oblast, Ukraine

Lviv Railway Clinical Hospital

Lviv, Lviv Oblast, Ukraine

Lviv Regional Endocrinology Dispensary

Lviv, Lviv Oblast, Ukraine

Medical Center of LLC Medical Center Clinic of Family Medicine

Dnipro, , Ukraine

International Institute of Clinical Trials LLC

Kyiv, , Ukraine

Communal Enterprise "Odesa Regional Clinical Hospital"

Odesa, , Ukraine

A. Novak Transcarpathian Regional Clinical Hospital

Uzhhorod, , Ukraine

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

Vinnytsia, , Ukraine

Vinnytsia War Veterans Regional Clinical Hospital

Vinnytsia, , Ukraine

Diacenter LLC

Zaporizhzhia, , Ukraine

Royal Derby Hospital

Derby, Derbyshire, United Kingdom

Whipps Cross University Hospital

Leytonstone, London, United Kingdom

Guys/St. Thomas Hospital

London, Surrey, United Kingdom

St. George's Hospital

London, , United Kingdom

York Hospital

York, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; China; Czechia; France; Georgia; Hungary; India; Israel; Japan; Latvia; Poland; Romania; Russia; Slovakia; South Korea; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/V3FQqG8aJfjj6JtJ60xFt

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

Other Identifiers

J1P-MC-KFAH

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003017-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17287

Identifier Type: -

Identifier Source: org_study_id