Inflammatory bowel disease
Conditions
Interventions
Participants will be randomized in a 6:3:2 ratio to receive, respectively:
• A high dose Mirikizumab intravenously every 4 weeks for 3 doses, then a lower
dose subcutaneously every 4 weeks
• A high
Sponsors
Eli Lilly
Eligibility
Age
16 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. (AMAM Main Trial): have given written informed consent approved by the Ethical Review Board (ERB) governing the site. 1. (AMAM Adolescent Addendum): the investigator, or a person designated by the investigator, will obtain written informed consent approved by the Ethical Review Board (ERB) from each study participant or the participant's parent/legal guardian and the subject*s assent, when applicable, before any study-specific activity is performed. The investigator will retain the original copy of each participant's signed consent/assent document. 2. (AMAM Main Trial): are male or female patients >=18 and 40 kgs with moderate to severely active CD as defined in points 5 and 6 below at the time of initial screening/consent. [2a] male patients: no male contraception required except in compliance with specific local government study requirements, [2b] female patients: women of childbearing potential: A. must test negative for pregnancy prior to initiation of treatment as indicated by a negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test within 24 hours prior to exposure. AND B. must agree to either remain abstinent, if complete abstinence is their preferred and usual lifestyle, or remain in same-sex relationships, if part of their preferred and usual lifestyle, without sexual relationships with males. Periodic abstinence (for example, calendar, ovulation, symptothermal, or post-ovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception. OR must use 2 effective methods of contraception for the entirety of the study. Abstinence or contraception must continue following completion of study drug administration for 20 weeks. i. Two effective methods of contraception (such as male or female condoms with spermicide, diaphragms with spermicide, or cervical sponges) will be used. The participant may choose to use a double barrier method of contraception. Barrier protection methods without concomitant use of a spermicide are not a reliable or acceptable method. Thus, each barrier method must include use of a spermicide. It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable because of the high failure rate when these methods are combined. ii. Of note, 1 of the 2 methods of contraception may be a highly effective (less than 1% failure rate) method of contraception (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices). women not of childbearing potential may participate and include those who are: A. infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or B postmenopausal - defined as either: i. a woman at least 40 years of age with an intact uterus, not on hormone therapy, who has had either * cessation of menses for at least 1 year without an alternative medical cause AND * at least 6 months of spontaneous amenorrhea with a folliclestimulating hormone (FSH) level >40 mIU/mL; or ii. a woman 55 years or older n
Exclusion criteria
Exclusion criteria: Participants will be excluded from study enrollment if they meet any of the following criteria within the screening period, unless otherwise specified below. For rescreening activities within the screening period, see Section 5.4. Gastrointestinal Exclusion Criteria [12] are participants who: [12a] have a current diagnosis of UC, IBD-unclassified (formerly known as indeterminate colitis). [12b] currently have or are suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained, adequately treated and resolved at least 3 weeks prior to baseline or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. [13] have a stoma, ileoanal pouch or ostomy. [14] have had a bowel resection within 6 months, or any kind of intra-abdominal surgery within 3 months of baseline (Visit 2). [15] have complications of CD such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery within 6 months after screening, could preclude the use of the SES-CD, CDAI, or PRO to assess response to therapy, or would possibly confound the ability to assess the effect of treatment. Adenoma, Dysplasia, and Gastrointestinal Cancer Exclusion Criteria [16] have any history or current evidence of cancer of the gastrointestinal tract. [17] have any current sporadic adenoma without dysplasia that has not been removed. Once completely removed, the patient is eligible for study. [18] have any evidence of colonic dysplasia. Criteria for Discontinuing Prohibited Medications [19] have received any of the following for treatment of CD within the time frames specified below: [19a] corticosteroid enemas, corticosteroid suppositories or a course of IV corticosteroids within 2 weeks prior to screening endoscopy. [19b] 5-ASA enemas or 5-ASA suppositories within 2 weeks prior to screening endoscopy. [19c] immunomodulatory medications, including oral cyclosporine, IV cyclosporine, tacrolimus, mycophenolate mofetil, thalidomide or Janus kinase inhibitors within 4 weeks prior to the screening endoscopy. * AZA, 6-MP, and MTX are allowed at stable doses (Appendix 10.7). * Other immunomodulatory medications should be discussed with the sponsor prior to screening. [19d] anti-TNF antibodies (for example, infliximab, adalimumab, or certolizumab pegol) within 4 weeks prior to screening endoscopy. [19e] anti-integrin antibodies (for example, vedolizumab) within 4 weeks prior to screening endoscopy. [19f] agents that deplete B or T cells (for example, rituximab, alemtuzumab, or visilizumab) within 12 months of baseline (Visit 2). Patients remain excluded if there is evidence of persistent targeted lymphocyte depletion at the time of screening endoscopy. [19g] any investigational nonbiologic therapy within 4 weeks prior to the screening endoscopy or within 5 half-lives prior to the screening endoscopy, whichever is longer. [19h] any investigational biologic therapy within 8 weeks prior to the screening endoscopy or within 5 half-lives prior to the screening endoscopy, whichever is longer. [19i] leukocyte apheresis (leukapheresis, for example, Adacolumn) within 3 weeks prior to screening endoscopy. [19j] in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study: 1. Percentage of Participants Achieving Clinical Response and Endoscopic Response Clinical response by Patient Reported Outcome (PRO) based on stool frequency (SF) and abdominal pain (AP) Endoscopic response based on Simple Endoscopic Score for Crohn's Disease (SES-CD) total score 2. Percentage of Participants Achieving Clinical Response and Clinical Remission Clinical response by PRO based on SF and AP Clinical remission based on CDAI Adolescent Addendum: Co-Primary • The coprimary endpoint at Week 52 of: o The proportion of patients achieving endoscopic response defined as a >=50% reduction from baseline in SES-CD total score AND o The proportion of patients achieving clinical remission by Patient Reported Outcome (PRO) (defined as SF | — |
Secondary
| Measure | Time frame |
|---|---|
| Main study: 1. Proportion of participants achieving endoscopic response based on Simple Endoscopic Score for Crohn's Disease SES-CD) total score 2. Proportion of participants achieving clinical remission by CDAI 3. Proportion of participants achieving endoscopic response based on SES-CD total score 4. Proportion of participants achieving endoscopic remission based on SES-CD total score 5. Percentage of Participants achieving clinical remission based on CDAI 6. Change from baseline in Urgency NRS 7. Percentage of Participants Achieving Clinical Response and Clinical Remission based on PRO 8. Percentage of Participants Achieving Clinical Response by PRO and Endoscopic Remission by SES-CD 9. Percentage of Participants Who Are Corticosteroid-free AND in Clinical Response by PRO AND either in Clinical Remission by CDAI or Endoscopic Remission by SES-CD 10. Change from Baseline in C-Reactive Protein 11. Change from Baseline in Fecal Calprotectin 12. Percentage of Participants Achieving Clinical Response by PRO with Extraintestinal Manifestations (EIMs) of Crohn's Disease 13. Percentage of participants achieving clinical response by PRO with fistulae response 14. Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Mirikizumab 15. Change from Baseline in Health Related Quality of Life based on Inflammatory Bowel Disease Questionnaire (IBDQ) score Adolescent Addendum: Secondary • Proportion of patients achieving endoscopic response at Week 12 • Proportion of patients achieving clinical remission by PRO at Week 12 • Proportion of patients achieving endoscopic remission SES-CD 1) at Week 52 • Proportion of patients taking corticosteroids at baseline achieving clinical remission by PRO or endoscopic remission SES-CD | — |
Countries
Netherlands
Outcome results
None listed