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A Study of Mirikizumab (LY3074828) in Participants With Active Crohn's Disease (SERENITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02891226
Recruitment Status : Completed
First Posted : September 7, 2016
Results First Posted : February 28, 2022
Last Update Posted : August 30, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to evaluate the safety and effectiveness of the study drug Mirikizumab in participants with active Crohn's Disease.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Mirikizumab Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 191 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Parallel-Arm, Placebo-Controlled Study of LY3074828 in Subjects With Active Crohn's Disease (SERENITY)
Actual Study Start Date : December 14, 2016
Actual Primary Completion Date : December 11, 2018
Actual Study Completion Date : February 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Mirikizumab

Period 1 (Weeks 0 -12): 200 Milligram (mg), 600 mg, and 1000 mg mirikizumab administered intravenously (IV) every 4 Weeks (Q4W).

Period 2 (Weeks 12 - 52): 200 mg, 600 mg, and 1000 mg mirikizumab administered IV Q4W; 300 mg mirikizumab administered subcutaneously (SC) Q4W; 1000 mg mirikizumab administered IV Q4W for non-improvers in period 1; and 1000 mg mirikizumab administered IV Q4W for participants on placebo during period 1.

Period 3 (Weeks 52 - 208): 300 mg mirikizumab administered SC Q4W.

Drug: Mirikizumab
Other Name: LY3074828

Placebo Comparator: Placebo
Period 1 (Weeks 0 -12): Participants received placebo administered intravenously (IV) Q4W.
Drug: Placebo



Primary Outcome Measures :
  1. Percentage of Participants Achieving Endoscopic Response at Week 12 [ Time Frame: Week 12 ]
    Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; >2 cm = score 3); extent of ulcerated surface (none = 0; <10% = 1;10-30% = 2;>30% = 3);extent of affected surface (none = 0; <50% = 1;50-75% = 2;>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]
    Endoscopic remission defined as SES-CD of <4 ileal-colonic or <2 for isolated ileal disease, and no subscore >1 at week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: (ileum; right, transverse, and left colon; and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; greater than (>) 2 cm = score 3); extent of ulcerated surface (none = 0; less than (<) 10% = 1; 10-30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50-75% = 2; >75% = 3); and presence and type of narrowings (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.

  2. Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 [ Time Frame: Week 12 ]
    PRO remission is defined as stool frequency (SF) ≤2.5 and abdominal pain (AP) ≤1 and no worse than baseline at week 12. SF captures the number of liquid or very soft stools. AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe.

  3. Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    The PGRS is a 1-item patient-rated questionnaire designed to assess the participant's rating of their disease symptom severity over the past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the subject has no symptoms (that is, "none") and a score of 6 indicates that the participant's symptom are "very severe." Least Squares Mean (LS Mean) was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

  4. Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    The PGRC scale is a patient-rated instrument designed to assess the participant's rating of change in their symptom(s). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the participant's symptom is "very much better," a score of 4 indicates that the participant's symptom has experienced "no change," and a score of 7 indicates that the participant's symptom is "very much worse."

  5. Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    The IBDQ is a 32-item self-administered questionnaire. The IBDQ has 4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). Responses are graded on a 7-point Likert scale in which 7 denotes "not a problem at all" and 1 denotes "a very severe problem." Scores range from 32 to 224; a higher score indicates a better quality of life. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

  6. Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 [ Time Frame: Baseline, Week 12 ]
    The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0-4 associated with a range over "Not at all" to "Very much" for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

  7. Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 [ Time Frame: Baseline, Week 12 ]
    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains:physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.

  8. Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab [ Time Frame: Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion ]
    Population mean (between-subject coefficient variance [CV %]) apparent clearance. Clearance is estimated based on concentration data collected in the time frame of 0-208 weeks.

  9. Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab [ Time Frame: Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion ]
    Population mean (between-subject coefficient variance [CV %]) apparent volume of distribution. Volume of distribution is estimated based on concentration data collected in the time frame of 0-208 weeks.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Active Crohn's Disease (CD) as determined by the SES-CD, and participant reported stool frequency and abdominal pain.
  • Inadequate response or failure to tolerate at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate); or prior exposure to biologics for the treatment of CD.

Exclusion Criteria:

  • Have complications of CD such as strictures, stenoses, or any other manifestation for which surgery might be indicated, or that could confound the evaluation of efficacy.
  • Diagnosis of conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome.
  • Have had any kind of bowel resection, diversion, or placement of a stoma within 6 months or any other intra-abdominal surgery within 3 months prior to screening.
  • Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02891226


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] July 11, 2018
Statistical Analysis Plan  [PDF] March 16, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02891226    
Other Study ID Numbers: 16492
I6T-MC-AMAG ( Other Identifier: Eli Lilly and Company )
2016-002204-84 ( EudraCT Number )
First Posted: September 7, 2016    Key Record Dates
Results First Posted: February 28, 2022
Last Update Posted: August 30, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Keywords provided by Eli Lilly and Company:
inflammatory bowel disease
IL-23
biologic
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Mirikizumab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Anti-Ulcer Agents
Gastrointestinal Agents