A Study of LY3471851 in Adult Participants With Moderatel... | NCT04677179 | Trialant
NCT04677179
Sponsor
Nektar Therapeutics
Status
Terminated
Last Update Posted
Sep 5, 2023Actual
Enrollment
81Actual
Phase
Phase 2
Conditions
Colitis, Ulcerative
Interventions
LY3471851
Placebo
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
Protocol Section
Identification Module
NCT ID
NCT04677179
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
17287
Secondary IDs
ID
Type
Description
Link
J1P-MC-KFAH
Other Identifier
Eli Lilly and Company
2020-003017-35
EudraCT Number
Brief Title
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
Acronym
INSTRUCT-UC
Organization
Nektar TherapeuticsINDUSTRY
Status Module
Record Verification Date
Aug 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Study terminated due to enrollment futility.
Expanded Access Info
No
Start Date
Mar 22, 2021Actual
Primary Completion Date
Aug 9, 2022Actual
Completion Date
Aug 9, 2022Actual
First Submitted Date
Dec 8, 2020
First Submission Date that Met QC Criteria
Dec 17, 2020
First Posted Date
Dec 21, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Aug 8, 2023
Results First Submitted that Met QC Criteria
Aug 8, 2023
Results First Posted Date
Sep 5, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 8, 2023
Last Update Posted Date
Sep 5, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Nektar TherapeuticsINDUSTRY
Collaborators
Name
Class
Eli Lilly and Company
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 Module
Conditions
Colitis, Ulcerative
Keywords
T regulatory cells (Tregs)
Interleukin 2
Interleukin-2
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
81Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
High dose LY3471851
Experimental
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
Low dose LY3471851
Experimental
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
Placebo
Placebo Comparator
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
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LY3471851
Drug
administered SC
High dose LY3471851
Low dose LY3471851
Placebo
Outcomes Module
Primary Outcomes
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 Outcomes
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.
Other Outcomes
Not provided
Eligibility Module
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.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
75 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Study Director
Nektar Therapeutics
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Dedicated Clinical Research
Litchfield Park
Arizona
85340
United States
I.H.S. Health, LLC
References Module
Citations
Not provided
See Also Links
Label
URL
A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC) ( INSTRUCT-UC )
(ii) Week 12 non-responders enter the extension period where they received high dose LY3471851. At week 26, those who responded to treatment continued with the same treatment, while non-responders discontinued and entered follow-up.
a 6-week post-treatment follow-up period: Following treatment completion or discontinuation, participants entered the follow-up period and were observed for safety. No treatments were administered.
Recruitment Details
The study consisted of:
a 12-week induction treatment period: participants randomly received either high dose LY3471851 or low dose LY3471851 or placebo.
a 40-week maintenance/extension treatment period (final dose at week 50 and study assessments at week 52)
(i) Week 12 responders enter the maintenance period where they continued to receive the same treatment to which they were randomly assigned.
(Continued..)
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
High Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12.
FG001
Low Dose LY3471851 (Induction Treatment Period)
Periods
Title
Milestones
Reasons Not Completed
Induction Treatment Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jun 3, 2021
Jun 2, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Germany
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
NKTR-358
Placebo
Drug
administered SC
Placebo
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.
A. Novak Transcarpathian Regional Clinical Hospital
Uzhhorod
88018
Ukraine
CCH #1 Vinnytsia M.I. Pyrogov NMU Ch of Propaedeutics of IM
Vinnytsia
21029
Ukraine
Vinnytsia War Veterans Regional Clinical Hospital
Vinnytsia
Ukraine
Diacenter LLC
Zaporizhzhia
69076
Ukraine
Royal Derby Hospital
Derby
Derbyshire
DE22 3NE
United Kingdom
Whipps Cross University Hospital
Leytonstone
London
E11 1NR
United Kingdom
Guys/St. Thomas Hospital
London
Surrey
SE1 9RT
United Kingdom
St. George's Hospital
London
SW17 0QT
United Kingdom
York Hospital
York
YO31 8HE
United Kingdom
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
FG002
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
FG003
High Dose LY3471851 (Maintenance Treatment Period)
Week 12 responders from the high dose LY3471851 induction treatment period arm entered the maintenance period and continued with the same treatment.
FG004
Low Dose LY3471851 (Maintenance Treatment Period)
Week 12 responders from the low dose LY3471851 induction treatment period arm entered the maintenance period and continued with the same treatment.
FG005
Placebo (Maintenance Treatment Period)
Week 12 responders from the placebo induction treatment period arm entered the maintenance period and continued with the same treatment.
FG006
High Dose LY3471851 (Extension Treatment Period)
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.
FG007
High Dose LY3471851 (Post-Treatment Follow-up Period)
Participants randomised to high dose LY3471851 arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.
Participants randomised to low dose LY3471851 arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.
FG009
Placebo (Post-Treatment Follow-up Period)
Participants randomised to placebo arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.
FG00725 subjectsParticipants entered the post-treatment follow-up period from induction or maintenance, or extension treatment periods.
FG00830 subjectsParticipants entered the post-treatment follow-up period from induction or maintenance, or extension treatment periods.
FG00911 subjectsParticipants entered the post-treatment follow-up period from induction or maintenance, or extension treatment periods.
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
All randomized participants.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
High Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12.
BG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
BG002
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00032
BG00135
BG00214
BG00381
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG00032
ParticipantsBG00135
ParticipantsBG00214
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
ParticipantsBG00032
ParticipantsBG00135
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
No
Title
Denominators
Categories
ParticipantsBG00032
ParticipantsBG00135
ParticipantsBG002
Region of Enrollment
All randomized participants with non-missing region of enrollment data.
Count of Participants
Participants
No
Title
Denominators
Categories
Argentina
ParticipantsBG00031
ParticipantsBG00135
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12.
Units
Counts
Participants
OG00014
OG00128
OG00229
Title
Denominators
Categories
Title
Measurements
OG00014.3(0 to 32.6)
OG0017.1(0 to 16.7)
OG00217.2(3.5 to 31)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
0.750
Odds Ratio (OR)
0.57
2-Sided
95
0.03
11.32
Superiority
OG000
OG002
Cochran-Mantel-Haenszel
0.838
Secondary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG002
High Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had Geboes data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
Secondary
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).
All randomized participants who received at least one dose of study drug and had Geboes, MMS data at week 12.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Secondary
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.
All randomized participants who received at least one dose of study drug and had IBDQ data at baseline, week 12.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 12
ID
Title
Description
OG000
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
OG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
Secondary
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.
All participants who received at least 1 dose of LY3471851 and had evaluable PK data.
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter (µg/mL)
Predose at week 12
ID
Title
Description
OG000
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
OG001
High Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12.
Units
Counts
Participants
OG000
Time Frame
Baseline to Follow-up (Up To Week 58)
Description
All randomized participants who received at least one dose of study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
High Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12.
0
32
2
32
20
32
EG001
Low Dose LY3471851 (Induction Treatment Period)
Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12.
0
35
0
35
15
35
EG002
Placebo (Induction Treatment Period)
Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12.
0
14
0
14
5
14
EG003
High Dose LY3471851 (Maintenance Treatment Period)
Week 12 responders from the high dose LY3471851 induction treatment period arm entered the maintenance period and continued with the same treatment.
0
8
0
8
4
8
EG004
Low Dose LY3471851 (Maintenance Treatment Period)
Week 12 responders from the low dose LY3471851 induction treatment period arm entered the maintenance period and continued with the same treatment.
0
10
1
10
6
10
EG005
Placebo (Maintenance Treatment Period)
Week 12 responders from the placebo induction treatment period arm entered the maintenance period and continued with the same treatment.
0
5
0
5
1
5
EG006
High Dose LY3471851 (Extension Treatment Period)
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.
0
26
0
26
5
26
EG007
High Dose LY3471851 (Post-Treatment Follow-up Period)
Participants randomised to high dose LY3471851 arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.
Participants randomised to low dose LY3471851 arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.
0
30
1
30
1
30
EG009
Placebo (Post-Treatment Follow-up Period)
Participants randomised to placebo arm entered follow-up period from induction or maintenance, or extension periods and were observed for 6 weeks for safety. No treatments were administered.