A Study of Mirikizumab (LY3074828) in Children and Teenagers With Ulcerative Colitis (UC) (SHINE-1)

A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric Patients With Moderately to Severely Active Ulcerative Colitis

This study was designed to evaluate how the body processes and removes mirikizumab. The study also evaluated safety and disease response in pediatric participants with UC taking mirikizumab. The study lasted about 52 weeks and included up to 18 visits.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Mirikizumab

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • University of Alberta Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel
    • The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition; Shaare Zedek Medical Center
  • Petah Tiqva, Israel, 4920235
    • Schneider Children's Medical Center
• Japan
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2308765
      • Saiseikai Yokohamashi Tobu Hospital
  • Saitama
    • Saitama-shi, Saitama, Japan, 330 8777
      • Saitama Children's Medical Center
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Bunkyō, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University Hospital
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Medical Center Chilgok Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • Childrens Hospital of Orange County
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • Children's Center for Digestive Health Care, LLC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospital
  • Indiana
    • Carmel, Indiana, United States, 46302
      • Riley Hospital for Children
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Waltham, Massachusetts, United States, 02451
      • MGH for Children - Waltham
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Goryeb Children's Hospital / Atlantic Health System
  • New York
    • New York, New York, United States, 10029
      • Icahn Sch of Med at Mt. Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • The Abbigail Wexner Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital
    • Houston, Texas, United States, 77030
      • Texas Childrens Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Pediatrics Specialists of Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters Inc
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants weighing >10 kg
• Participants must have a diagnosis of ulcerative colitis for at least 3 months before the planned start date for the study medications
• Participants must have moderately to severely active UC as defined by a Modified Mayo Score (MMS) within 14 days before the first dose of study treatment
• Participants must have evidence of UC extending proximal to the rectum
• Participants must have demonstrated an inadequate response to, a loss of response to, or an intolerance to corticosteroids, immunomodulators, Janus kinase inhibitor (JAK-inhibitor) or to biologic therapies for UC

Exclusion Criteria:

• Participants must not have a current diagnosis of Crohn's disease, inflammatory bowel disease-unclassified (indeterminate colitis), ulcerative proctitis, or primary sclerosing cholangitis
• Participants must not have had surgery to remove part of their colon
• Participants must not have current evidence of toxic megacolon
• Participants must not have received any of the following for treatment of UC: cyclosporine or thalidomide within 30 days of screening; corticosteroid enemas, corticosteroid suppositories, or topical treatment with 5-aminosalicyclic acid within 1 week of screening endoscopy
• Participants must not have had an inadequate response to Interleukin-12 p40 subunit antibody (anti-IL12p40) (e.g. ustekinumab) or had prior exposure to anti-IL-23p19 antibodies (e.g. risankizumab, brazikumab, guselkumab or tildrakizumab)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label (OL) Induction Period: 5 milligram per kilogram (mg/kg) Miri intravenous (IV); Participants (≤40 kg weight) received 5 mg/kg mirikizumab given as an IV infusion every 4 weeks (Q4W) on weeks 0, 4, 8 for 12 weeks.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Induction Period: 10 mg/kg Miri IV; Participants (≤40 kg weight) received 10 mg/kg mirikizumab given as an IV infusion Q4W on weeks 0, 4, 8 for 12 weeks.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Induction Period: 300 mg Miri IV; Participants (>40 kg weight) received 300 mg mirikizumab given as an IV infusion Q4W on weeks 0, 4, 8 for 12 weeks.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: 50 mg Miri subcutaneous (SC); Participants (≤20 kg weight) who were responders to mirikizumab at week 12 in induction received 50 mg subcutaneously (SC) Q4W from week 12 through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: 100 mg Miri SC; Participants (>20 to ≤40 kg weight) who were responders to mirikizumab at week 12 in induction received 100 mg SC Q4W from week 12 through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: 200 mg Miri SC; Participants (>40 kg weight) who were responders to mirikizumab at week 12 in induction received 200 mg SC Q4W from week 12 through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: Non-Responders: 10 mg/kg Miri IV/ 50 mg Miri SC; Participants (≤40 kg) who were non responders to miri at Week 12 in induction received 10 mg SC Q4W for 12 weeks or discontinued after repeat induction, and then received 50 mg miri (≤20 kg weight) SC Q4W through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: Non-Responders: 10 mg/kg Miri IV/100 mg Miri SC; Participants (≤40 kg) who were non responders to miri at week 12 in induction received 10 mg SC Q4W for 12 weeks or discontinued after repeat induction, and then received 100 mg miri (>20 to ≤40 kg weight) SC Q4W through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828
Experimental: Open Label Maintenance Period: Non-Responders: 300 mg Miri IV /200 mg Miri SC; Participants (>40 kg) who were non responders to miri at week 12 in induction received 300 mg SC Q4W for 12 weeks or discontinued after repeat induction, then received 200 mg miri SC Q4W through week 48 or until loss of response was confirmed.	Drug: Mirikizumab; Administered IV and SC; Other Names: LY3074828

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Clearance of Mirikizumab	Clearance of mirikizumab was evaluated. The PK of mirikizumab is characterized at interim analysis points using mixed-effect (population PK) modelling approaches using the available induction and maintenance mirikizumab concentration data.	Predose on week 4, 8, 12,16, 24, 36, 52 and post dose on week 0 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Clinical Remission	Clinical remission at week 52 is defined as achieving a 9-point modified Mayo score (MMS) for rectal bleeding (RB) = 0, stool frequency (SF) = 0 or 1 and endoscopy (ES) = 0 or 1 (excluding friability). The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three subscores: SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed); ES subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration.	Week 52
Percentage of Participants in Clinical Response	Clinical response at week 52 is defined as a decrease in the 9-point modified Mayo score (MMS) [rectal bleeding, stool frequency and the endoscopic findings] inclusive of ≥2 points and ≥30% from baseline with either a decrease of rectal bleeding subscore of ≥1 or rectal bleeding subscore of 0 or 1. The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three subscores: SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed); ES subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration)	Week 52
Percentage of Participants Who Are in MMS Clinical Remission Without the Use of Corticosteroids	Corticosteroid-free clinical remission was defined as an SF subscore = 0 or 1, RB subscore = 0, ES ≤ 1 (excluding friability), and have not received corticosteroids for ≥ 12 weeks in the 52-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.	Week 52
Percentage of Participants in Clinical Remission Based on the Pediatric Ulcerative Colitis Activity Index (PUCAI)	The PUCAI is a clinician-administered, 6-item questionnaire that measures: abdominal pain; RB; stool consistency; number of stools; nocturnal stools; and activity level. For PUCAI score all items are answered as an average over the 'past 2 days'. A total disease activity score is calculated from 0 to 85, with Severe 65-85; Moderate:35-60; Mild:10-30, and None:<10. The clinician will record the participant or caregiver/legal guardian responses for the PUCAI electronically as source data in the tablet device at appropriate visits. PUCAI clinical remission is defined as a PUCAI score of <10 points.	Week 52
Percentage of Participants in Clinical Response Based on the PUCAI	PUCAI clinical response is defined as a reduction in baseline PUCAI score of ≥20 points.	Week 52
Percentage of Participants in Endoscopic Remission	Endoscopic remission at week 52 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) at Week 52. ES subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).	Week 52
Percentage of Participants in Symptomatic Remission	Symptomatic remission at week 52 is defined as a Mayo score for RB=0, SF=0 or 1 with ≥ 1 point decrease from baseline. SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal). RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed).	Week 52
Height Velocity (in Centimeters/Year)	Observed height velocity by gender and age group was calculated. Age groups for which this was summarized were 2 to <8, 8 to <12, and 12 to <18. Observed height velocity by gender and age group was calculated at baseline according to the following formula: (Present Height [cm] - Previous Height [cm])/Interval (months) Between Measurements × 12.	Week 52
Change From Baseline in Body Weight	Change from Baseline in body weight by gender and age group was calculated.	Baseline, Week 52
Percentage of Participants With Histologic-Endoscopic Mucosal Remission	Histologic-endoscopic mucosal remission is defined as achieving both histologic remission and endoscopic remission. Histologic remission is defined as Geboes histological subscores of 0 for parameters: 2B (neutrophils in lamina propria), 3 (neutrophils in epithelium), 4 (crypt destruction), and 5 (erosion or ulceration).	Week 52
Change From Baseline in 7-day Average of Abdominal Pain Numeric Rating Scale (NRS) Score at Week 12	The Abdominal Pain NRS is a single participant-reported item that measures the "worst abdominal pain in the past 24 hours" using a 6-point scale ranging from 0 (no pain) to 5 (worst possible pain) for 8-11 years old, and 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) for children < 8 years old as completed by a caregiver and those 12-17 years old. Abdominal Pain NRS Score is calculated by averaging data from all available daily diary entries of abdominal pain NRS for a 7 day period. A negative change from baseline indicates improvement in the participant's Abdominal Pain NRS.	Baseline, Week 12
Change From Baseline in 7-day Average of Abdominal Pain NRS Score at Week 52	The Abdominal Pain NRS is a single participant-reported item that measures the "worst abdominal pain in the past 24 hours" using a 6-point scale ranging from 0 (no pain) to 5 (worst possible pain) for 8-11 years old, and 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) for children < 8 years old as completed by a caregiver and those 12-17 years old. Abdominal Pain NRS Score is calculated by averaging data from all available daily diary entries of abdominal pain NRS for a 7 day period. A negative change from baseline indicates improvement in the participant's Abdominal Pain NRS.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: 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

Publications and helpful links

Helpful Links

• A Study of Mirikizumab (LY3074828) in Children and Teenagers With Ulcerative Colitis (UC)

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: June 29, 2019
• First Submitted That Met QC Criteria: June 29, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; Interleukin-23 (IL-23) antibody; IL-23p19
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Anti-Ulcer Agents; Mirikizumab
• Other Study ID Numbers: 17410 (Other Identifier: City of Hope Comprehensive Cancer Center); I6T-MC-AMBU (Other Identifier: Eli Lilly and Company); 2019-001298-96 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No