Clinical trial NCT04677179: A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Official title: An Adaptive Phase 2, Randomized, Double Blind, Placebo Controlled Study of LY3471851 (NKTR 358) in Patients With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: T regulatory cells (Tregs)
Interleukin 2
Interleukin-2
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2020-12-21
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Who Achieved Clinical Remission at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved Clinical Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Endoscopic Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Endoscopic Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Symptomatic Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Symptomatic Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Histologic Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing (HEMH)
timeFrame: Week 12
measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) - Total Score
timeFrame: Baseline, Week 12
measure: Pharmacokinetics (PK): Trough Concentration of LY3471851 (Ctrough) at Week 12
timeFrame: Predose at week 12
Other outcomes:
Locations:
city: Litchfield Park
country: United States
facility: Dedicated Clinical Research
state: Arizona
city: Kissimmee
country: United States
facility: I.H.S. Health, LLC
state: Florida
city: Pensacola
country: United States
facility: Gastroenterology Associates of Pensacola, PA
state: Florida
city: Morristown
country: United States
facility: Atlantic Digestive Health Institute
state: New Jersey
city: Houston
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC
state: Texas
city: Ogden
country: United States
facility: Care Access Research - Ogden
state: Utah
city: Caba
country: Argentina
facility: DOM- Centro de Reumatologia
state: Buenos Aires
city: Caba
country: Argentina
facility: Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC
state: Buenos Aires
city: Ciudad Autonoma De Buenos Air
country: Argentina
facility: Mautalen Salud e Investigacion-Centro de Osteopatías Médicas
state: Buenos Aires
city: Tucumán
country: Argentina
facility: Centro Médico Privado de Reumatología
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Albion
country: Australia
facility: Paratus Clinical Research Brisbane
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital Brisbane
state: Queensland
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Brussels
country: Belgium
facility: Université Libre de Bruxelles - Hôpital Erasme
state: Bruxelles-Capitale, Région De
city: Tournai
country: Belgium
facility: Centre Hospitalier de Wallonie Picarde - Site Notre Dame
state: Wallonne, Région
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Brasília
country: Brazil
facility: Chronos Pesquisa Clínica
state: Distrito Federal
city: Porto Alegre
country: Brazil
facility: Nucleo de Pesquisa Clínica do Rio Grande do Sul-NPCRS
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: HMCP - Hospital e Maternidade Celso Pierro - PUC-Campinas
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Pesquisare
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto de Assistencia Medica ao Servidor Publico Estudo Estadual
state: SP
city: Botucatu
country: Brazil
facility: Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
state: São Paulo
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hepatogastro
city: Edmonton
country: Canada
facility: Gastroenterology and internal medicine research institute
state: Alberta
city: Halifax
country: Canada
facility: Gastroenterology Research, Nova Scotia Health Authority
state: Nova Scotia
city: Greenfield Park
country: Canada
facility: CISSS de la Montérégie - Centre Hôpital Charles-Le Moyne
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: HefeiCity
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Guangzhou
country: China
facility: First affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Wu Han
country: China
facility: Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Taian
country: China
facility: Taian City Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine Ruijin Hospital
state: Shanghai
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Pilsen
country: Czechia
facility: A-Shine
state: Plzeň-město
city: Olomouc
country: Czechia
facility: MUDr. Gregar, s.r.o.
city: Olomouc
country: Czechia
facility: PreventaMed, s.r.o.
city: Plzen-Lochotin
country: Czechia
facility: I. Interni klinika FN Plzen
city: Slany
country: Czechia
facility: Nemocnice Slaný
city: Grenoble Cedex 09
country: France
facility: CHU De Grenoble Hopital Albert Michallon
city: Mont-de-Marsan Cedex
country: France
facility: Centre Hospitalier de Mont de Marsan
city: Tbilisi
country: Georgia
facility: Acad. F. Todua Medical Center - Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: Medical Center: Medinvestment
city: Budapest
country: Hungary
facility: Clinexpert SMO
city: Budapest
country: Hungary
facility: Óbudai Egészségügyi Centrum
city: Gyöngyös
country: Hungary
facility: Bugát Pál Kórház
city: Szekszard
country: Hungary
facility: CLINFAN Szolgáltató Kft
city: Rajkot
country: India
facility: Shree Giriraj Multispeciality Hospital
state: Gujarat
city: Surat
country: India
facility: Gujarat Hospital - Gastro and Vascular Centre
state: Gujarat
city: Nagpur
country: India
facility: Kingsway Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Midas Multispeciality Hospital Pvt.Ltd.
state: Maharashtra
city: Jaipur
country: India
facility: SR Kalla Memorial Gastro & General Hospital
state: Rajasthan
city: Chennai
country: India
facility: Apollo Speciality Hospital - Teynampet
state: Tamil Nadu
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education & Research
city: Telangana
country: India
facility: Gandhi Hospital
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center - Internal A
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Chikushino
country: Japan
facility: Fukuoka University Chikushi Hospital
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Tokushukai Sapporo Tokushukai Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Osaka-shi
country: Japan
facility: Infusion Clinic
state: Osaka-Fu
city: Fujiidera
country: Japan
facility: Sai Gastroenterologist Proctology
state: Osaka
city: Hamamatsu-shi
country: Japan
facility: Matsuda Hospital
state: Shizuoka-Ken
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo-To
city: Koto-ku
country: Japan
facility: Showa University Koto Toyosu Hospital
state: Tokyo
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Kagoshima
country: Japan
facility: Sameshima Hospital
city: Toyama
country: Japan
facility: Toyama Prefectural Central Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
state: Korea
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Gangwon-do
country: Korea, Republic of
facility: Yonsei University Wonju Severance Christian Hospital
city: Riga
country: Latvia
facility: Pauls Stradins Clinical Univeristy Hospital
state: Rīga
city: Warsaw
country: Poland
facility: NZOZ Vivamed
state: Mazowieckie
city: Elblag
country: Poland
facility: Szpital Miejski Sw. Jana Pawla II
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Zamosc
country: Poland
facility: ETG Zamość
city: Oradea
country: Romania
facility: SC Pelican SRL
state: Bihor
city: Bucuresti
country: Romania
facility: SC Med Life SA
city: Bucuresti
country: Romania
facility: SC Centrul Medical Sana SRL
city: Bucuresti
country: Romania
facility: Spital Clinic Colentina
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj
city: Timisoara
country: Romania
facility: S.C. Materna Care S.R.L.
city: Moscow
country: Russian Federation
facility: Olla-Med
state: Moskva
city: Novosibirsk
country: Russian Federation
facility: Novosibirski Gastrocenter
state: Novosibirskaya Oblast'
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
state: Rostovskaya Oblast'
city: Moscow
country: Russian Federation
facility: Open Joint Stock Company Clinical and Diagnostic Center Euromedservice
city: Omsk
country: Russian Federation
facility: The University Clinic of OSMU
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBIH "City Mariinskaya Hospital"
city: St. Petersburg
country: Russian Federation
facility: GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen of Health
city: Banska Bystrica
country: Slovakia
facility: FNsP FDRoosevelta Banska Bystrica
city: Kosice
country: Slovakia
facility: ENDOMED s.r.o.
city: Kiev
country: Ukraine
facility: Medical Center of Limited Liability Company "Medical Center "Consilium Medical"
state: Kyiv
city: Lviv
country: Ukraine
facility: Lviv Railway Clinical Hospital
state: Lvivska Oblast
city: Lviv
country: Ukraine
facility: Lviv Regional Endocrinology Dispensary
state: Lvivska Oblast
city: Dnipro
country: Ukraine
facility: Medical Center of LLC Medical Center Clinic of Family Medicine
city: Kyiv
country: Ukraine
facility: International Institute of Clinical Trials LLC
city: Odesa
country: Ukraine
facility: Communal Enterprise "Odesa Regional Clinical Hospital"
city: Uzhgorod
country: Ukraine
facility: A. Novak Transcarpathian Regional Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
city: Vinnytsia
country: Ukraine
facility: Vinnytsia War Veterans Regional Clinical Hospital
city: Zaporizhzhia
country: Ukraine
facility: Diacenter LLC
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
state: Derbyshire
city: Leytonstone
country: United Kingdom
facility: Whipps Cross University Hospital
state: London
city: London
country: United Kingdom
facility: Guys/St. Thomas Hospital
state: Surrey
city: London
country: United Kingdom
facility: St. George's Hospital
city: York
country: United Kingdom
facility: York Hospital
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References: