A Study of Mirikizumab (LY3074828) in Children and Teenagers With Ulcerative Colitis (UC)
- Registration Number
- NCT04004611
- Lead Sponsor
- Eli Lilly and Company
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open Label Induction Period: 10 mg/kg Miri IV Mirikizumab Participants (≤40 kg weight) received 10 mg/kg mirikizumab given as an IV infusion Q4W on weeks 0, 4, 8 for 12 weeks. Open Label (OL) Induction Period: 5 milligram per kilogram (mg/kg) Miri intravenous (IV) Mirikizumab 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. Open Label Induction Period: 300 mg Miri IV Mirikizumab Participants (\>40 kg weight) received 300 mg mirikizumab given as an IV infusion Q4W on weeks 0, 4, 8 for 12 weeks. Open Label Maintenance Period: 50 mg Miri subcutaneous (SC) Mirikizumab 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. Open Label Maintenance Period: 100 mg Miri SC Mirikizumab 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. Open Label Maintenance Period: 200 mg Miri SC Mirikizumab 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. Open Label Maintenance Period: Non-Responders: 300 mg Miri IV /200 mg Miri SC Mirikizumab 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. Open Label Maintenance Period: Non-Responders: 10 mg/kg Miri IV/ 50 mg Miri SC Mirikizumab 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. Open Label Maintenance Period: Non-Responders: 10 mg/kg Miri IV/100 mg Miri SC Mirikizumab 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.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Clearance of Mirikizumab Predose on week 4, 8, 12,16, 24, 36, 52 and post dose on week 0 and 8 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants in Clinical Remission Week 52 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.
Percentage of Participants in Clinical Response Week 52 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)
Percentage of Participants Who Are in MMS Clinical Remission Without the Use of Corticosteroids Week 52 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.
Percentage of Participants in Clinical Remission Based on the Pediatric Ulcerative Colitis Activity Index (PUCAI) Week 52 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.
Percentage of Participants in Clinical Response Based on the PUCAI Week 52 PUCAI clinical response is defined as a reduction in baseline PUCAI score of ≥20 points.
Percentage of Participants in Symptomatic Remission Week 52 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).Height Velocity (in Centimeters/Year) Week 52 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.
Change From Baseline in Body Weight Baseline, Week 52 Change from Baseline in body weight by gender and age group was calculated.
Percentage of Participants in Endoscopic Remission Week 52 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).
Percentage of Participants With Histologic-Endoscopic Mucosal Remission Week 52 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).
Change From Baseline in 7-day Average of Abdominal Pain Numeric Rating Scale (NRS) Score at Week 12 Baseline, 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.
Change From Baseline in 7-day Average of Abdominal Pain NRS Score at Week 52 Baseline, 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.
Trial Locations
- Locations (37)
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Riley Hospital for Children
🇺🇸Carmel, Indiana, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Chicago Hospital
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
UCSF Medical Center at Mission Bay
🇺🇸San Francisco, California, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Texas Childrens Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital Research Foundation
🇺🇸Seattle, Washington, United States
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
National Center For Child Health And Development
🇯🇵Setagaya-ku, Tokyo, Japan
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyō, Tokyo, Japan
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Saiseikai Yokohamashi Tobu Hospital
🇯🇵Yokohama, Kanagawa, Japan
Saitama Children's Medical Center
🇯🇵Saitama-shi, Saitama, Japan
Emory University
🇺🇸Atlanta, Georgia, United States
Children's Center for Digestive Health Care, LLC
🇺🇸Atlanta, Georgia, United States
MGH for Children - Waltham
🇺🇸Waltham, Massachusetts, 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
The Abbigail Wexner Research Institute at Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Cook Children's Hospital
🇺🇸Fort Worth, Texas, United States
Pediatrics Specialists of Virginia
🇺🇸Fairfax, Virginia, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Children's Hospital of The King's Daughters Inc
🇺🇸Norfolk, Virginia, United States
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Rambam Medical Center
🇮🇱Haifa, Israel
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition; Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Schneider Children's Medical Center
🇮🇱Petah Tiqva, Israel
Kyungpook National University Medical Center Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Children's Hospital of Colorado
🇺🇸Denver, Colorado, United States
Tokyo Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan