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

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ClinicalTrials.gov Identifier: NCT04677179
Recruitment Status : Recruiting
First Posted : December 21, 2020
Last Update Posted : September 5, 2021
Sponsor:
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE December 8, 2020
First Posted Date  ICMJE December 21, 2020
Last Update Posted Date September 5, 2021
Actual Study Start Date  ICMJE March 22, 2021
Estimated Primary Completion Date November 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2020)
Percentage of Participants in Clinical Remission [ Time Frame: Week 12 ]
Clinical remission is based on a combination of stool frequency subscore (SF), rectal bleeding (RB) subscore and Mayo endoscopic subscore (ES). SF ranges from 0 (normal) to 3 (5 or mores stools than normal). RB ranges from 0 (no blood seen) to 3 (blood alone passed) and Mayo endoscopic score ranges from 0 (normal) to 3 (severe with spontaneous bleeding and ulceration).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2020)
  • Percentage of Participants Who Achieved Clinical Response [ Time Frame: Week 12 ]
    Clinical response is based on the Modified Mayo Score (MMS) which ranges from 0 (normal) to 9 (most severe) and is defined as a decrease in the MMS of ≥2 points and ≥30% decrease from baseline, and a decrease of ≥1 point in the RB subscore from baseline or a RB score of 0 or 1. RB score ranges from 0 (normal) to 3 (blood alone passed).
  • Percentage of Participants Who Achieved Endoscopic Remission [ Time Frame: Week 12 ]
    Endoscopic remission is based on MMS and is defined as a decrease in the Mayo endoscopic score (ES) of >= 1 point compared to baseline. The Mayo endoscopic score ranges from 0 (normal) to 3 (severe with spontaneous bleeding and ulceration).
  • Percentage of Participants Who Achieved Endoscopic Response [ Time Frame: Week 12 ]
    Endoscopic response is based on MMS defined as Mayo endoscopic subscore (ES) = 0 or 1, excluding friability.
  • Percentage of Participants Who Achieved Symptomatic Response [ Time Frame: Week 12 ]
    Symptomatic response is based on MMS and is defined as stool frequency (SF) = 0 or SF = 1 with a decrease of ≥1 point from baseline, and rectal bleeding (RB) = 0. Stool frequency score ranges from 0 (normal) to 3 (5 or mores stools than normal) and RB ranges from 0 (no blood seen) to 3 (blood alone passed).
  • Percentage of Participants Who Achieved Symptomatic Remission [ Time Frame: Week 12 ]
    Symptomatic remission is based on MMS and is defined as ≥30% decrease from baseline in the composite clinical endpoint of the sum of SF which ranges from 0 (normal) to 3 (5 or more stools than normal) and an RB subscore which ranges from 0 (no blood seen) to 3 (blood alone passed).
  • Percentage of Participants Who Achieved Histologic Remission [ Time Frame: Week 12 ]
    Histologic remission is based on MMS and is defined as Geboes score <2 or Geboes subscores = 0 for Grade 2a, 2b, 3 4 and 5. Geboes histologic scoring index is a six grade classification system for inflammation with subscores within each grade. The grades are: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers.
  • Percentage of Participants Who Achieved Histologic-Endoscopic Mucosal Healing [ Time Frame: Week 12 ]
    Histologic-endoscopic mucosal is based on MMS and is defined as Geboes score <2 AND endoscopic remission. Geboes histologic scoring index is a six grade classification system for inflammation with subscores within each grade. The grades are: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Endoscopic remission is based on MMS and is defined as a decrease in the Mayo endoscopic score (ES) of >= 1 point compared to baseline.
  • Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline, Week 12 ]
    Mean change from baseline in IBDQ: A 32-item patient-completed questionnaire that measures 4 aspects of participants' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function. Responses are graded on a 7-point Likert scale in which 7 denotes "not a problem at all" and 1 denotes "a very severe problem." Scores range from 32 to 224; a higher score indicates a better quality of life.
  • Pharmacokinetics (PK) of LY3471851 Trough Concentration [ Time Frame: Week 12 ]
    PK: Ctrough of LY3471851
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY3471851 in Adult Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Official Title  ICMJE An Adaptive Phase 2, Randomized, Double Blind, Placebo Controlled Study of LY3471851 (NKTR 358) in Patients With Moderately to Severely Active Ulcerative Colitis
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE
  • Drug: LY3471851
    administered SC
    Other Name: NKTR-358
  • Drug: Placebo
    administered SC
Study Arms  ICMJE
  • Experimental: LY3471851 (High Dose)

    Stage 1 LY3471851 given subcutaneously (SC)

    Stage 2 LY3471851 multiple doses to be confirmed

    Intervention: Drug: LY3471851
  • Experimental: LY3471851 (Low Dose)

    Stage 1 LY3471851 given subcutaneously (SC)

    Stage 2 LY3471851 multiple doses to be confirmed

    Intervention: Drug: LY3471851
  • Placebo Comparator: Placebo

    Stage 1 Placebo given SC

    Stage 2 Placebo given SC

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 17, 2020)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 23, 2024
Estimated Primary Completion Date November 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Georgia,   Hungary,   India,   Israel,   Japan,   Korea, Republic of,   Latvia,   Poland,   Romania,   Russian Federation,   Slovakia,   Ukraine,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT04677179
Other Study ID Numbers  ICMJE 17287
J1P-MC-KFAH ( Other Identifier: Eli Lilly and Company )
2020-003017-35 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Nektar Therapeutics
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date September 1, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP