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

An Adaptive Phase 2, Randomized, Double Blind, Placebo Controlled Study of LY3471851 (NKTR 358) in Patients With Moderately to Severely Active Ulcerative Colitis

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.

Study Overview

• Status: Terminated
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: LY3471851; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Tucumán, Argentina, T4000AXL
    • Centro Médico Privado de Reumatología
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, 1111
      • DOM- Centro de Reumatologia
    • Caba, Buenos Aires, Argentina, C1431FWO
      • Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" Cemic
    • Ciudad Autonoma De Buenos Air, Buenos Aires, Argentina, C1128AAF
      • Mautalen Salud e Investigacion-Centro de Osteopatías Médicas
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • Albion, Queensland, Australia, 4010
      • Paratus Clinical Research Brisbane
    • South Brisbane, Queensland, Australia, 4700
      • Mater Adult Hospital Brisbane
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
• Belgium
  • Gent, Belgium, 9100
    • AZ Maria Middelares
  • Bruxelles-Capitale, Région De
    • Brussels, Bruxelles-Capitale, Région De, Belgium, 1070
      • Université Libre de Bruxelles - Hôpital Erasme
  • Wallonne, Région
    • Tournai, Wallonne, Région, Belgium, 7500
      • Centre Hospitalier de Wallonie Picarde - Site Notre Dame
• Brazil
  • Sao Paulo, Brazil, 04543-001
    • Hepatogastro
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil, 72145-450
      • Chronos Pesquisa Clínica
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
  • SP
    • Sao Paulo, SP, Brazil, 04039-004
      • Instituto de Assistencia Medica ao Servidor Publico Estudo Estadual
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13060-904
      • HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
    • Santo Andre, Sao Paulo, Brazil, 09080-110
      • Pesquisare
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-687
      • Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
    • São Bernardo do Campo, São Paulo, Brazil, 09715-090
      • CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5R 1W2
      • Gastroenterology and internal medicine research institute
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H2Y9
      • Gastroenterology Research, Nova Scotia Health Authority
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V2H1
      • CISSS de la Montérégie - Centre Hôpital Charles-Le Moyne
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University
• China
  • Anhui
    • HefeiCity, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital, Sun Yat-sen University
  • Hubei
    • Wu Han, Hubei, China, 430030
      • Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Shandong
    • Taian, Shandong, China, 271000
      • Taian City Central Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Shanghai Jiaotong University School of Medicine Ruijin Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital
• Czechia
  • Olomouc, Czechia, 779 00
    • MUDr. Gregar, s.r.o.
  • Olomouc, Czechia, 779 00
    • PreventaMed, s.r.o.
  • Plzen-Lochotin, Czechia, 304 60
    • I. Interni klinika FN Plzen
  • Slany, Czechia, 274 01
    • Nemocnice Slany
  • Plzeň-město
    • Pilsen, Plzeň-město, Czechia, 312 00
      • A-Shine
• France
  • Grenoble Cedex 09, France, 38043
    • CHU de Grenoble Hopital Albert Michallon
  • Mont-de-Marsan Cedex, France, 40024
    • Centre Hospitalier de Mont de Marsan
• Georgia
  • Tbilisi, Georgia, 0112
    • Acad. F. Todua Medical Center - Research Institute of Clinical Medicine
  • Tbilisi, Georgia, 0186
    • Medical Center: Medinvestment
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert SMO
  • Budapest, Hungary, 1036
    • Óbudai Egészségügyi Centrum
  • Gyöngyös, Hungary, 3200
    • Bugat Pal Korhaz
  • Szekszard, Hungary, 7100
    • CLINFAN Szolgáltató Kft
• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education & Research
  • Telangana, India, 500003
    • Gandhi Hospital
  • Gujarat
    • Rajkot, Gujarat, India, 360004
      • Shree Giriraj Multispeciality Hospital
    • Surat, Gujarat, India, 395009
      • Gujarat Hospital - Gastro and Vascular Centre
  • Maharashtra
    • Nagpur, Maharashtra, India, 440001
      • Kingsway Hospital
    • Nagpur, Maharashtra, India, 440010
      • Midas Multispeciality Hospital Pvt.Ltd.
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • SR Kalla Memorial Gastro & General Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600035
      • Apollo Speciality Hospital - Teynampet
• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center
  • Nahariya, Israel, 22100
    • Galilee Medical Center - Internal A
  • Rehovot, Israel, 7610001
    • Kaplan Medical Center
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Kagoshima, Japan, 892-0846
    • Sameshima Hospital
  • Toyama, Japan, 930-8550
    • Toyama Prefectural Central Hospital
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Fukuoka
    • Chikushino, Fukuoka, Japan
      • Fukuoka University Chikushi Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Sapporo Medical University Hospital
    • Sapporo-shi, Hokkaido, Japan, 004 0041
      • Tokushukai Sapporo Tokushukai Hospital
  • Osaka
    • Fujiidera, Osaka, Japan, 583-0027
      • Sai Gastroenterologist Proctology
  • Osaka-Fu
    • Osaka-shi, Osaka-Fu, Japan, 530-0011
      • Infusion Clinic
  • Shizuoka-Ken
    • Hamamatsu-shi, Shizuoka-Ken, Japan, 4328061
      • Matsuda Hospital
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135 8577
      • Showa University Koto Toyosu Hospital
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital
  • Tokyo-To
    • Shinjuku-ku, Tokyo-To, Japan, 162 8655
      • Center Hospital of the National Center for Global Health and Medicine
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Gangwon-do, Korea, Republic of, 26426
    • Yonsei University Wonju Severance Christian Hospital
  • Gyeonggi-do
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 443380
      • Ajou University Hospital
  • Korea
    • Seoul, Korea, Korea, Republic of, 06351
      • Samsung Medical Center
    • Seoul, Korea, Korea, Republic of, 06591
      • Seoul ST. Mary's hospital
• Latvia
  • Rīga
    • Riga, Rīga, Latvia, LV-1002
      • Pauls Stradins Clinical Univeristy Hospital
• Poland
  • Elblag, Poland, 82-300
    • Szpital Miejski Sw. Jana Pawla II
  • Warszawa, Poland, 00-728
    • WIP Warsaw IBD Point Profesor Kierkus
  • Zamosc, Poland, 22-400
    • ETG Zamość
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 03-580
      • NZOZ Vivamed
• Romania
  • Bucuresti, Romania, 010719
    • SC Med Life SA
  • Bucuresti, Romania, 011025
    • SC Centrul Medical Sana SRL
  • Bucuresti, Romania
    • Spital Clinic Colentina
  • Cluj-Napoca, Romania, 400006
    • Spitalul Clinic Judetean de Urgenta Cluj
  • Timisoara, Romania, 300645
    • S.C. Materna Care S.R.L.
  • Bihor
    • Oradea, Bihor, Romania, 410469
      • SC Pelican SRL
• Russian Federation
  • Moscow, Russian Federation
    • Open Joint Stock Company Clinical and Diagnostic Center Euromedservice
  • Omsk, Russian Federation, 644050
    • The University Clinic of OSMU
  • Saint-Petersburg, Russian Federation, 194104
    • Spb SBIH "City Mariinskaya Hospital"
  • St. Petersburg, Russian Federation, 195067
    • GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen of Health
  • Moskva
    • Moscow, Moskva, Russian Federation, 105554
      • Olla-Med
  • Novosibirskaya Oblast'
    • Novosibirsk, Novosibirskaya Oblast', Russian Federation, 630007
      • Novosibirski Gastrocenter
  • Rostovskaya Oblast'
    • Rostov-on-Don, Rostovskaya Oblast', Russian Federation, 344091
      • Rostov State Medical University
• Slovakia
  • Banska Bystrica, Slovakia, 97517
    • FNsP FDRoosevelta Banska Bystrica
  • Kosice, Slovakia, 04013
    • ENDOMED s.r.o.
• Ukraine
  • Dnipro, Ukraine
    • Medical Center of LLC Medical Center Clinic of Family Medicine
  • Kyiv, Ukraine, 02091
    • International Institute of Clinical Trials LLC
  • Odesa, Ukraine, 65000
    • Communal Enterprise "Odesa Regional Clinical Hospital"
  • Uzhgorod, Ukraine, 88018
    • A. Novak Transcarpathian Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21029
    • CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
  • Vinnytsia, Ukraine
    • Vinnytsia War Veterans Regional Clinical Hospital
  • Zaporizhzhia, Ukraine, 69076
    • Diacenter LLC
  • Kyiv
    • Kiev, Kyiv, Ukraine, 4050
      • Medical Center of Limited Liability Company "Medical Center "Consilium Medical"
  • Lvivska Oblast
    • Lviv, Lvivska Oblast, Ukraine, 79000
      • Lviv Railway Clinical Hospital
    • Lviv, Lvivska Oblast, Ukraine, 79000
      • Lviv Regional Endocrinology Dispensary
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • St. George's Hospital
  • York, United Kingdom, YO31 8HE
    • York Hospital
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • Royal Derby Hospital
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Whipps Cross University Hospital
  • Surrey
    • London, Surrey, United Kingdom, SE1 9RT
      • Guys/St. Thomas Hospital
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Dedicated Clinical Research
  • Florida
    • Kissimmee, Florida, United States, 34741
      • I.H.S. Health, LLC
    • Pensacola, Florida, United States, 32503
      • Gastroenterology Associates of Pensacola, PA
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Digestive Health Institute
  • Texas
    • Houston, Texas, United States, 77084
      • Biopharma Informatic, LLC
    • San Antonio, Texas, United States, 78229
      • Southern Star Research Institute, LLC
  • Utah
    • Ogden, Utah, United States, 84403
      • Care Access Research - Ogden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: LY3471851; administered SC; Other Names: NKTR-358
Experimental: 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.	Drug: LY3471851; administered SC; Other Names: NKTR-358
Placebo Comparator: 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.	Drug: LY3471851; administered SC; Other Names: NKTR-358; Drug: Placebo; administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Clinical Response at Week 12	Clinical response is defined as a decrease in the MMS of ≥2 points and ≥30% decrease from baseline, and a decrease of ≥1 point in the rectal bleeding sub-score from baseline or a rectal bleeding score of 0 or 1. 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
Percentage of Participants Who Achieved Endoscopic Remission at Week 12	Endoscopic remission is defined as achieving a MMS sub-score for 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
Percentage of Participants Who Achieved Endoscopic Response at Week 12	Endoscopic response is defined as a decrease of ≥1 point in the MMS endoscopy sub-score from baseline. 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
Percentage of Participants Who Achieved Symptomatic Remission at Week 12	Symptomatic remission is defined as achieving a MMS sub-score for stool frequency=0, or stool frequency=1 with a decrease of ≥1 point from baseline, and rectal bleeding =0. 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
Percentage of Participants Who Achieved Symptomatic Response at Week 12	Symptomatic response is defined as a ≥30% decrease from baseline in the composite clinical endpoint of the sum of MMS sub-scores of stool frequency and rectal bleeding. 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
Percentage of Participants Who Achieved Histologic Remission at Week 12	Histologic Remission is defined as Geboes score <2 or subscores = 0 for Grade 2a, 2b, 3, 4, and 5. The Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7 items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease.	Week 12
Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing (HEMH)	HEMH is defined as Geboes score <2 AND endoscopic remission. Geboes score is a 7-item instrument used to identify histologic changes in UC. The 7-items are Grade 0: Architectural changes (0=No abnormality to 3=Severe diffuse or multifocal abnormalities); Grade 1: Chronic inflammatory infiltrate (0=No increase to 3=Marked increase); Grade 2A: lamina propria eosinophils (0=No increase to 3=Marked increase); Grade 2B: lamina propria neutrophils (0= No increase to 3=Marked increase); Grade 3: Neutrophils in epithelium (0=None to 3=>50% crypts involved); Grade 4: Crypt destruction(0=none to 3=Unequivocal crypt destruction),and Grade 5: Erosion or ulceration:(0=No erosion, ulceration or granulation to 4=Ulcer or granulation tissue). The grade with severe histological observation is considered the Geboes score and ranges from 0 to 4, with higher scores indicating severe disease. Endoscopic remission is defined as achieving a MMS sub-score for endoscopy=0 or 1 (excluding friability).	Week 12
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) - Total Score	IBDQ is a 32-item questionnaire that measures four aspects of participants' lives: symptoms directly related to the primary bowel disturbance (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Responses are graded on a 7-point Likert scale, where 7 denotes "not a problem at all" and 1 denotes "a very severe problem." The responses are summed to produce a total score ranging from 32 to 224, with higher score indicating a better quality of life. LS Mean was calculated using ANCOVA (analysis of covariance) model with treatment, baseline value, previous advanced therapy failure status (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: [4 to 6] or [7 to 9]) and region (North America/Europe/Other) as fixed factors.	Baseline, Week 12
Pharmacokinetics (PK): Trough Concentration of LY3471851 (Ctrough) at Week 12	C-trough is the concentration of drug in the blood immediately before the next dose was administered.	Predose at week 12

Collaborators and Investigators

• Sponsor: Nektar Therapeutics
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Study Director, Nektar Therapeutics

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: T regulatory cells (Tregs); Interleukin 2; Interleukin-2
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 17287; J1P-MC-KFAH (Other Identifier: Eli Lilly and Company); 2020-003017-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No