An investigational study to assess the safety and effectiveness of an investigational drug in people with moderate to severe ulcerative colitis

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-003123-57-BE
• Date of registration: 01/10/2015
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: An investigational study to assess the safety and effectiveness of an investigational drug in people with moderate to severe ulcerative colitis
• Scientific title: A Phase 2, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Study of LY3074828 in Subjects with Moderate to Severe Ulcerative Colitis - AMAC
• Date of first enrolment: 09/02/2016
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003123-57
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, Denmark, France, Georgia, Hungary, Japan, Lithuania, Moldova, Republic of, Netherlands, Poland, Romania, Russian Federation, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
(1) have given written informed consent approved by the ERB (ethical review board) governing the site
(2) are male or female subjects =18 and =75 years of age at the time of initial screening
(2a) Male subjects agree to use a reliable method of birth control during the study and for 3 months, which is greater than 5 half-lives, after the last dose of investigational product.
(2b) female subjects:
- are women of childbearing potential whose serum pregnancy test results are negative and who agree to use a reliable method of birth control (eg, condom, sponge, or diaphragm combined with spermicidal foam, gel, or cream; ongoing hormonal contraception [oral, intramuscular, depot, or transdermal], such as Depo-Provera, Evra, or NuvaRing; an intrauterine device; or complete abstinence from sexual intercourse with men) during the study and for 3 months after the last dose of the investigational product
OR
- are not women of childbearing potential, defined as having: bilateral oophorectomy, tubal ligation, or hysterectomy at least 6 weeks before screening; spontaneous amenorrhea for = 12 months, not induced by a medical condition or medications; or spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level greater than 40 mIU/mL at screening
(3) venous access sufficient to allow blood sampling and IV administration (if applicable), as per the protocol
(4) have had a diagnosis of UC for =3 months before baseline (endoscopic evidence corroborated by a histopathology report); a biopsy for a local histopathology evaluation (to obtain a report) can be obtained during the baseline endoscopy procedure if a histopathology report is not available
(5) have moderate to severe active UC as defined by a Mayo score of 6 to 12 with an endoscopic subscore =2 within 14 days before the first dose of study treatment (note: a partial Mayo score of at least 4 and other eligibility criteria must have been met before endoscopy is performed as a study procedure)
(6) have evidence of UC extending proximal to the rectum (=15 cm of involved colon)
(7) have documentation of a surveillance colonoscopy (performed according to local standard) within 12 months before baseline (may be performed during screening) for subjects with pancolitis of >8 years’ duration or left-sided colitis of >12 years’ duration
(7a) up-to-date colorectal cancer surveillance (performed according to local standard), for subjects with family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor
(8) subjects must either:
(8a) be naive to biologic therapy (such as TNF antagonists, vedolizumab, or experimental UC biologics) and have at least 1 of the following:
- inadequate response or failure to tolerate current treatment with oral or IV corticosteroids or immunomodulators (6-MP or AZA) or
- history of corticosteroid dependence (an inability to successfully taper corticosteroids without return of UC)
OR
(8b) have received treatment with 1 or more biologic agents (such as TNF antagonists, vedolizumab, or experimental UC biologics) at doses approved for the treatment of UC with or without documented history of fa
Exclusion criteria:
(12) have been diagnosed with indeterminate colitis, proctitis (distal disease involving the rectum only; less than 15 cm from the anal verge) or CD
(13) have had surgery for treatment of UC or are likely to require surgery for UC during the study
(14) have received any of the following for treatment of UC:
(14a) cyclosporine or thalidomide within 30 days of screening endoscopy
(14b) corticosteroid enemas, corticosteroid suppositories, or topical treatment with 5-ASA within 30 days of screening endoscopy
(14c) have used apheresis (eg, Adacolumn apheresis) =2 weeks before screening
(15) have previous exposure to any biologic therapy targeting IL-23 (including ustekinumab), either licensed or investigational
(16) have been treated with any investigational drug for UC within 30 days or 5 half-lives of the drug (whichever is longer) before the initial screening visit (Visit 1), OR with interferon therapy within 8 weeks before baseline
(17) have evidence of abdominal abscess or toxic megacolon during screening
(18) have extensive colonic resection, subtotal or total colectomy, ileostomy, colostomy, or fixed symptomatic stenosis of the intestine
(19) have evidence of active or latent TB (refer to Section 10.3.2.2 of the protocol for details on full TB exclusion criteria)
(20) have had any malignancy within 5 years of screening, except for basal cell or squamous epithelial carcinoma of the skin that has been resected with no evidence of metastatic disease for at least 3 years OR cervical carcinoma in situ with no evidence of recurrence within 5 years of screening
(21) are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
(22) are Lilly employees or employees of third -party organizations (TPOs) involved with the study
(23) are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device, OR are concurrently enrolled in any other type of medical research not scientifically or medically compatible with this study, per investigator judgment
(24) have previously completed or withdrawn from this study or any other study investigating LY3074828. This criterion does not apply to subjects undergoing rescreening procedures.
(25) have received live, attenuated vaccine(s) within 2 months of screening or intend to receive such during the study; vaccines should be avoided for 2 months after the last dose of study drug. Uses of nonlive (inactivated) vaccinations are allowed for all subjects
(26) have HIV/AIDS or test positive for human immunodeficiency virus antibodies at screening
(27) have hepatitis B or test positive for hepatitis B virus (HBV) at screening, defined as: (1) positive for hepatitis B surface antigen or (2) positive for anti–hepatitis B core antibody (HBcAb+) and positive confirmatory polymerase chain reaction (PCR) for HBV, regardless of anti–hepatitis B surface antibody status
(28) have hepatitis C or test positive hepatitis C virus at screening, defined as: positive result for hepatitis C antibody and positive confi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: Mirikizumab
Product Code: LY3074828
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Not assigned
Current Sponsor code: LY3074828
Other descriptive name: LY3074828
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is clinical remission at Week 12. Clinical remission is defined as having achieved the following Mayo subscores at Week 12: a rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 (with 1 point decrease from baseline), and endoscopy subscore of 0 or 1.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Objective: - To evaluate the safety and tolerability of treatment with LY3074828
- To evaluate the efficacy of treatment with LY3074828 in inducing a clinical response at Week 12 (as defined in Section 10.1.2 of the protocol)
- To evaluate endoscopic remission at Week 12 and Week 52 (as defined in Section 10.1.2)
- To evaluate the effect of maintenance treatment with LY3074828 on the durability of clinical remission, endoscopic remission, and response at Week 52
- To evaluate the effect of LY3074828 on health outcomes/quality of life measures (including: Inflammatory Bowel Disease Questionnaire [IBDQ] score, 36-Item Short Form Health Survey [SF-36] score, Patient’s Global Impressions of Severity [PGI-S] score, and Patient’s Global Impressions of Improvement [PGI-I] score).
- To characterize the PK profile of LY3074828

Main Objective: The primary objective of this study is to test the hypothesis that treatment with LY3074828 is superior to placebo in inducing clinical remission at Week 12 (as defined in Section 10.1.1 of the protocol) in subjects with moderate to severe UC.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints are clinical response at Week 12 and endoscopic remission at Week 12 and Week 52. Clinical response is defined as having achieved at Week 12 a decrease in 9-point Mayo subscore (rectal bleeding, stool frequency, and endoscopy) inclusive of =2 points and =35% from baseline with either a decrease of rectal bleeding subscore of =1 or a rectal bleeding subscore of 0 or 1. Endoscopic remission is defined as having achieved a Mayo endoscopic subscore of 0.

Timepoint(s) of evaluation of this end point: Week 12 and Week 52

Secondary ID(s)

I6T-MC-AMAC

NCT02589665

Source(s) of Monetary Support

Eli Lilly and Company

Ethics review

Status: Approved
Approval date:
Contact: