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

Ulcerative Colitis Clinical Trial

— SHINE-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04004611
• Other study ID #: 17410
• Secondary ID: I6T-MC-AMBU2019-
• Status: Completed
• Phase: Phase 2
• Start date: May 18, 2020
• Est. completion date: March 15, 2023

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 15, 2023
• Est. primary completion date: March 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Mirikizumab
Administered IV and SC

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	The Hospital for Sick Children	Toronto	Ontario
Israel	Rambam Medical Center	Haifa
Israel	The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition; Shaare Zedek Medical Center	Jerusalem
Israel	Schneider Children's Medical Center	Petah Tiqva
Japan	Tokyo Medical and Dental University Hospital	Bunkyo	Tokyo
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Saitama Children's Medical Center	Saitama-shi	Saitama
Japan	National Center For Child Health And Development	Setagaya-ku	Tokyo
Japan	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Saiseikai Yokohamashi Tobu Hospital	Yokohama	Kanagawa
Korea, Republic of	Kyungpook National University Medical Center Chilgok Hospital	Daegu
Korea, Republic of	Seoul National University Hospital	Seoul
United States	Children's Center for Digestive Health Care, LLC	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Riley Hospital for Children	Carmel	Indiana
United States	University of Chicago Hospital	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	The Abbigail Wexner Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Hospital of Colorado	Denver	Colorado
United States	Pediatrics Specialists of Virginia	Fairfax	Virginia
United States	Cook Children's Hospital	Fort Worth	Texas
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Texas Childrens Hospital	Houston	Texas
United States	Goryeb Children's Hospital / Atlantic Health System	Morristown	New Jersey
United States	Icahn Sch of Med at Mt. Sinai	New York	New York
United States	Children's Hospital of The King's Daughters Inc	Norfolk	Virginia
United States	Childrens Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCSF Medical Center at Mission Bay	San Francisco	California
United States	Seattle Children's Hospital Research Foundation	Seattle	Washington
United States	MGH for Children - Waltham	Waltham	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Body Weight	Change from Baseline in body weight by gender and age group was calculated.	Baseline, Week 52
Secondary	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
Secondary	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
Secondary	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

External Links

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