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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04677179




Registration number
NCT04677179
Ethics application status
Date submitted
8/12/2020
Date registered
21/12/2020

Titles & IDs
Public title
A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Scientific title
An Adaptive Phase 2, Randomized, Double Blind, Placebo Controlled Study of LY3471851 (NKTR 358) in Patients With Moderately to Severely Active Ulcerative Colitis
Secondary ID [1] 0 0
J1P-MC-KFAH
Secondary ID [2] 0 0
17287
Universal Trial Number (UTN)
Trial acronym
INSTRUCT-UC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colitis, Ulcerative 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3471851
Treatment: Drugs - Placebo

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.

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.

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.


Treatment: Drugs: LY3471851
administered SC

Treatment: Drugs: Placebo
administered SC

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved Clinical Remission at Week 12
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved Clinical Response at Week 12
Timepoint [1] 0 0
Week 12
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved Endoscopic Remission at Week 12
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved Endoscopic Response at Week 12
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Percentage of Participants Who Achieved Symptomatic Remission at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percentage of Participants Who Achieved Symptomatic Response at Week 12
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Percentage of Participants Who Achieved Histologic Remission at Week 12
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing (HEMH)
Timepoint [7] 0 0
Week 12
Secondary outcome [8] 0 0
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) - Total Score
Timepoint [8] 0 0
Baseline, Week 12
Secondary outcome [9] 0 0
Pharmacokinetics (PK): Trough Concentration of LY3471851 (Ctrough) at Week 12
Timepoint [9] 0 0
Predose at week 12

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Paratus Clinical Research Brisbane - Albion
Recruitment hospital [3] 0 0
Mater Adult Hospital Brisbane - South Brisbane
Recruitment hospital [4] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4010 - Albion
Recruitment postcode(s) [3] 0 0
4700 - South Brisbane
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Tucumán
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles-Capitale, Région De
Country [9] 0 0
Belgium
State/province [9] 0 0
Wallonne, Région
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Brazil
State/province [11] 0 0
Distrito Federal
Country [12] 0 0
Brazil
State/province [12] 0 0
Rio Grande Do Sul
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Paulo
Country [14] 0 0
Brazil
State/province [14] 0 0
SP
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Nova Scotia
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Anhui
Country [20] 0 0
China
State/province [20] 0 0
Guangdong
Country [21] 0 0
China
State/province [21] 0 0
Hubei
Country [22] 0 0
China
State/province [22] 0 0
Jiangxi
Country [23] 0 0
China
State/province [23] 0 0
Shandong
Country [24] 0 0
China
State/province [24] 0 0
Shanghai
Country [25] 0 0
China
State/province [25] 0 0
Zhejiang
Country [26] 0 0
Czechia
State/province [26] 0 0
Plzen-mesto
Country [27] 0 0
Czechia
State/province [27] 0 0
Olomouc
Country [28] 0 0
Czechia
State/province [28] 0 0
Plzen-Lochotin
Country [29] 0 0
Czechia
State/province [29] 0 0
Slany
Country [30] 0 0
France
State/province [30] 0 0
Grenoble Cedex 09
Country [31] 0 0
France
State/province [31] 0 0
Mont-de-Marsan Cedex
Country [32] 0 0
Georgia
State/province [32] 0 0
Tbilisi
Country [33] 0 0
Hungary
State/province [33] 0 0
Budapest
Country [34] 0 0
Hungary
State/province [34] 0 0
Gyöngyös
Country [35] 0 0
Hungary
State/province [35] 0 0
Szekszard
Country [36] 0 0
India
State/province [36] 0 0
Gujarat
Country [37] 0 0
India
State/province [37] 0 0
Maharashtra
Country [38] 0 0
India
State/province [38] 0 0
Rajasthan
Country [39] 0 0
India
State/province [39] 0 0
Tamil Nadu
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India
State/province [40] 0 0
Chandigarh
Country [41] 0 0
India
State/province [41] 0 0
Telangana
Country [42] 0 0
Israel
State/province [42] 0 0
Beer Sheva
Country [43] 0 0
Israel
State/province [43] 0 0
Nahariya
Country [44] 0 0
Israel
State/province [44] 0 0
Rehovot
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hokkaido
Country [47] 0 0
Japan
State/province [47] 0 0
Osaka-Fu
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Shizuoka-Ken
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo-To
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Japan
State/province [51] 0 0
Tokyo
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Japan
State/province [52] 0 0
Kagoshima
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Japan
State/province [53] 0 0
Toyama
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Japan
State/province [54] 0 0
Yamagata
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Korea, Republic of
State/province [55] 0 0
Gyeonggi-do
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Korea
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Busan
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Gangwon-do
Country [59] 0 0
Latvia
State/province [59] 0 0
Riga
Country [60] 0 0
Poland
State/province [60] 0 0
Mazowieckie
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Poland
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Elblag
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Poland
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Warszawa
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Poland
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Zamosc
Country [64] 0 0
Romania
State/province [64] 0 0
Bihor
Country [65] 0 0
Romania
State/province [65] 0 0
Bucuresti
Country [66] 0 0
Romania
State/province [66] 0 0
Cluj-Napoca
Country [67] 0 0
Romania
State/province [67] 0 0
Timisoara
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Moskva
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Novosibirskaya Oblast'
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Rostovskaya Oblast'
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Moscow
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Omsk
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Saint-Petersburg
Country [74] 0 0
Russian Federation
State/province [74] 0 0
St. Petersburg
Country [75] 0 0
Slovakia
State/province [75] 0 0
Banska Bystrica
Country [76] 0 0
Slovakia
State/province [76] 0 0
Kosice
Country [77] 0 0
Ukraine
State/province [77] 0 0
Kyiv
Country [78] 0 0
Ukraine
State/province [78] 0 0
Lvivska Oblast
Country [79] 0 0
Ukraine
State/province [79] 0 0
Dnipro
Country [80] 0 0
Ukraine
State/province [80] 0 0
Odesa
Country [81] 0 0
Ukraine
State/province [81] 0 0
Uzhgorod
Country [82] 0 0
Ukraine
State/province [82] 0 0
Vinnytsia
Country [83] 0 0
Ukraine
State/province [83] 0 0
Zaporizhzhia
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Derbyshire
Country [85] 0 0
United Kingdom
State/province [85] 0 0
London
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Surrey
Country [87] 0 0
United Kingdom
State/province [87] 0 0
York

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nektar Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Nektar Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.