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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
22/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/08/2022
Sample size
Target
Accrual to date
Final
81
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
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United States of America
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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
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Gent
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Brazil
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Distrito Federal
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Brazil
State/province [14] 0 0
SP
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
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Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
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Nova Scotia
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Canada
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Quebec
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China
State/province [19] 0 0
Anhui
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China
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Guangdong
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China
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Hubei
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China
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Jiangxi
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China
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Shandong
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China
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Shanghai
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China
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Zhejiang
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Czechia
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Plzen-mesto
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Czechia
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Olomouc
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Czechia
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Plzen-Lochotin
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Czechia
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Slany
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France
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Grenoble Cedex 09
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France
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Mont-de-Marsan Cedex
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Georgia
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Tbilisi
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Hungary
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Budapest
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Hungary
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Gyöngyös
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Hungary
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Szekszard
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India
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Gujarat
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India
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Maharashtra
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India
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Rajasthan
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India
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Tamil Nadu
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India
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Chandigarh
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India
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Telangana
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Israel
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Beer Sheva
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Israel
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Nahariya
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Israel
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Rehovot
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Japan
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Fukuoka
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Japan
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Hokkaido
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Japan
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Osaka-Fu
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Japan
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Osaka
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Japan
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Shizuoka-Ken
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Japan
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Tokyo-To
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Tokyo
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Kagoshima
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Toyama
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Japan
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Yamagata
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Korea
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Korea, Republic of
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Busan
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Gangwon-do
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Latvia
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Riga
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Poland
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Mazowieckie
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Elblag
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Warszawa
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Poland
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Zamosc
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Romania
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Bihor
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Romania
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Bucuresti
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Romania
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Cluj-Napoca
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Romania
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Timisoara
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Russian Federation
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Moskva
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Russian Federation
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Novosibirskaya Oblast'
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Russian Federation
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Rostovskaya Oblast'
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Russian Federation
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Moscow
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Russian Federation
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Omsk
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Russian Federation
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Saint-Petersburg
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Russian Federation
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St. Petersburg
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Slovakia
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Banska Bystrica
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Slovakia
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Kosice
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Ukraine
State/province [77] 0 0
Kyiv
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Ukraine
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Lvivska Oblast
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Ukraine
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Dnipro
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Ukraine
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Odesa
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Ukraine
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Uzhgorod
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Ukraine
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Vinnytsia
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Ukraine
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Zaporizhzhia
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United Kingdom
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Derbyshire
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United Kingdom
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London
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United Kingdom
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Surrey
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United Kingdom
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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.


Results are available at https://clinicaltrials.gov/study/NCT04677179