A Study to Evaluate the Efficacy and Safety of Mirikizumab (LY3074828) in Participants With Moderate-to-Severe Plaque Psoriasis

Phase 3

Completed

Conditions: Psoriasis

Interventions: Drug: Placebo
Drug: Mirikizumab

Registration Number: NCT03482011

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of mirikizumab in participants with moderate to severe plaque psoriasis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 530

Inclusion Criteria

Present with chronic plaque psoriasis based on an investigator confirmed diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline and meet the following criteria:
- plaque psoriasis involving ≥10% BSA and absolute PASI score ≥12 in affected skin at screening and baseline
- sPGA score of ≥3 at screening and baseline
Candidate for systemic therapy and/or phototherapy for psoriasis.

Exclusion Criteria

Have an unstable or uncontrolled illness, including but not limited to a cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic disease or abnormal laboratory values at screening, that in the opinion of the investigator, would potentially affect participant safety within the study or of interfering with the interpretation of data.
Breastfeeding or nursing women.
Have had serious, opportunistic, or chronic/recurring infection within 3 months prior to screening.
Have received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or received live vaccine(s) (including attenuated live vaccines) within 12 weeks of baseline or intend to receive either during the study.
Have any other skin conditions (excluding psoriasis) that would affect interpretation of the results.
Have received systemic nonbiologic psoriasis therapy or phototherapy within 28 days prior to baseline.
Have received topical psoriasis treatment within 14 days prior to baseline.
Have received anti-tumor necrosis factor (TNF) biologics, or anti-interleukin (IL)-17 targeting biologics within 12 weeks prior to baseline.
Have previous exposure to any biologic therapy targeting IL-23 (including ustekinumab), either licensed or investigational.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Induction Period: Participants received placebo administered SC Q4W. Maintenance Period: Participants received one of the two options below: Placebo administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q4W during week 16 to week 32 and Q8W during week 40 and 48 for non-responders (\< PASI 90).
Mirikizumab	Mirikizumab	Induction Period: Participants received 250 milligrams (mg) mirikizumab administered subcutaneously (SC) every 4 weeks (Q4W). Maintenance Period: Participants received one of the four options below: Placebo administered SC every 8 weeks (Q8W) for responders (≥PASI 90). 125 mg mirikizumab administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q8W for responders (≥PASI 90). 250 mg mirikizumab administered SC Q8W for non-responders (\<PASI 90).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline	Week 16	The sPGA is the physician's determination of the participant's psoriasis (PsO) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's PsO was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of "0" or "1" with at least a 2-point improvement from baseline.
Percentage of Participants Achieving a ≥90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90)	Week 16	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With ≤1% of Body Surface Area (BSA) With Psoriasis Involvement	Week 16	The BSA is the percentage involvement of psoriasis on each participant's body surface on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The total BSA affected was the summation of individual regions affected. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Percentage of Participants With a Psoriasis Symptoms Scale (PSS) Symptoms Score of 0 in Those With a PSS Symptoms Score ≥1 at Baseline	Week 16	PSS is a patient-administered assessment of 4 symptoms (itch, pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the discomfort related to symptoms/signs. The overall severity for each individual symptom/sign from the patient's psoriasis is indicated by selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst imaginable symptom/sign. In addition, a symptoms score ranging from 0 (no symptoms) to 40 (worst imaginable symptoms), and a signs score of 0 (no signs) to 30 (worst imaginable signs) will be reported. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Total Score of (0,1) With at Least a 5-Point Improvement (Reduction) From Baseline in Participants With a Baseline DLQI Total Score ≥5	Week 16	The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period	Week 52	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline	Week 16	The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 (no PPASI) to 72 (most severe PPASI). The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. Least Squares Mean (LS Mean) was calculated using mixed model repeated measures (MMRM) model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as covariates.
Percentage of Participants Achieving a ≥75% Improvement From Baseline in PASI (PASI 75)	Week 16	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Percentage of Participants Achieving a ≥100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100)	Week 16	PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis (PsO) to 72 for the most severe disease. For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region \* area score \* weighing factor \[head (0.1), upper limbs (0.2), trunk (0.3), lower limbs (0.4)\]. Overall scores range from 0 (no PsO) to 72 (the most severe disease).
Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline	Week 16	The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (\<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as covariates.
Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline	Week 16	The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix PsO by area of involvement. The fingernail is divided into quadrants. Each fingernail is given a score for fingernail bed PsO 0 (none) to 4 (PsO in 4 quadrants of the fingernail) and fingernail matrix PsO 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix PsO in each quadrant. The sum of all fingernails equals the total NAPSI score range is from 0 (no effect) to 80 (more severe psoriasis). LS Mean was calculated using MMRM model with treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit, and previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as covariates.
Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS)	Baseline, Week 16	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as fixed factors.
Change From Baseline on the SF-36 Mental Component Summary (MCS)	Baseline, Week 16	SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as fixed factors.
Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline	Baseline, Week 16	The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been). Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO)	Baseline, Week 16	The WPAI-PSO consists of 6 questions to determine employment status, hours missed from work because of psoriasis, hours missed from work for other reasons, hours actually worked, the degree to which psoriasis affected work productivity while at work, and the degree to which psoriasis affected activities outside of work. Four scores are derived: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism and impairment in activities performed outside of work. Each WPAI score is expressed as impairment percentages (0-100) with higher numbers indicating greater impairment and less productivity, that is, worse outcomes. LS Mean was calculated using Analysis of covariance (ANCOVA) model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as fixed factors.
Change From Baseline in Quick Inventory of Depressive Symptomology (QIDS-SR16) Total Score in Those With a Baseline QIDS-SR16 Total Score ≥11	Baseline, Week 16	QIDS-SR16 is a participant-administered, 16-item instrument intended to assess the existence and severity of symptoms of depression. A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days and rate each on a 4-point scale: 0 (best) to 3 (worst). The sum of the 16 items corresponding to 9 depression domains \[sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle and late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor agitation/retardation\] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity. Whereas 0-5 indicates no symptoms. LS Mean was calculated using ANCOVA model with treatment and baseline value, previous exposure to biologic therapy (yes/no), body weight (\<100 kg or \>=100 kg), and geographic region (North America or Other) as fixed factors.
Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1)	Week 16	The DLQI is a patient-reported, 10-question, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). A DLQI total score of 0 to 1 is considered as having no effect on a patient's health-related quality of life (HRQoL), and a 5-point change from baseline is considered as the minimal clinically important difference (MCID) threshold. Percentage response is calculated by number of participants with a response divided by number of participants with non-missing values multiplied by 100.
Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16	Week 16: Day 113	Minimum observed serum concentration at steady state (Ctrough,ss) of mirikizumab at Week 16.

Trial Locations

Locations (69): The South Bend Clinic
🇺🇸
South Bend, Indiana, United States
B&B Investigaciones Medicas, SC
🇲🇽
Mazatlan, Sinaloa, Mexico
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Gyeonggi-do, Korea, Republic of
Kume Clinic
🇯🇵
Nishi-ku Sakai-shi, Osaka, Japan
Korea University Guro Hospital
🇰🇷
Seoul, Korea, Korea, Republic of
Takagi Dermatological Clinic
🇯🇵
Obihiro, Hokkaido, Japan
Multicare Health System
🇺🇸
Tacoma, Washington, United States
Universitätsklinikum Münster
🇩🇪
Münster, Nordrhein-Westfalen, Germany
"Dermed" Centrum Medyczne Sp. z o.o.
🇵🇱
Lodz, Poland
GOU VPO 'Smolensk State Medical Academy of Ministry of Health and Social Development of Russian Federation'
🇷🇺
Smolensk, Russian Federation
Bundang CHA General Hospital
🇰🇷
Sungnam-si, Gyeonggi-do, Korea, Republic of
Kanto Rosai Hospital
🇯🇵
Kawasaki, Kanagawa, Japan
Forward Clinical Trials, Inc
🇺🇸
Tampa, Florida, United States
Universitätsklinikum Hamburg - Eppendorf
🇩🇪
Hamburg, Germany
Clinical Research Hamburg GmbH
🇩🇪
Hamburg, Germany
Renstar Medical Research
🇺🇸
Ocala, Florida, United States
Florida Academic Dermatology Centers
🇺🇸
Coral Gables, Florida, United States
University of Utah MidValley Dematology
🇺🇸
Murray, Utah, United States
ISA GmbH
🇩🇪
Berlin, Germany
Univ of Connecticut
🇺🇸
Farmington, Connecticut, United States
Ryukyu University Hospital
🇯🇵
Nakagami-gun, Okinawa, Japan
Tver State Medical University
🇷🇺
Tver, Russian Federation
Shirasaki Clinic
🇯🇵
Takaoka-shi, Toyama, Japan
Chungnam National University Hospital
🇰🇷
Daejeon, Korea, Republic of
NTT Medical Center Tokyo
🇯🇵
Shinagawa-KU, Tokyo, Japan
Praxis Gerlach
🇩🇪
Dresden, Sachsen, Germany
Toho University School of Medicine, Sakura Hospital
🇯🇵
Sakura, Chiba, Japan
Yokohama City University Hospital
🇯🇵
Yokohama, Kanagawa, Japan
Shimane University Hospital
🇯🇵
Izumo, Shimane, Japan
Bucheon St. Mary's Hospital
🇰🇷
Bucheon,, Gyeonggi-do, Korea, Republic of
Tokyo Medical University Hospital
🇯🇵
Shinjuku-ku, Tokyo, Japan
Seibo Hospital
🇯🇵
Shinjuku-ku, Tokyo, Japan
Kyung Hee University Hospital
🇰🇷
Seoul, Korea, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷
Seoul, Korea, Republic of
Hanyang University Medical Center
🇰🇷
Seoul, Korea, Republic of
Konkuk University Hospital
🇰🇷
Seoul, Korea, Republic of
Instituto Dermatologico de Jalisco Dr. Jose Barba Rubio
🇲🇽
Zapopan, Jalisco, Mexico
Clínica Enfermedades Crónicas y Procedimientos Especiales SC
🇲🇽
Morella, Michoacan, Mexico
Kohler Milstein Research, S.A. de C.V.
🇲🇽
Merida, Yucatan, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia A.C
🇲🇽
Durango, Mexico
RM Pharma Specialists S.A. de C.V.
🇲🇽
Distrito Federal, Mexico
NZOZ ZDROWIE Osteo-Medic
🇵🇱
Bialystok, Poland
Centrum Medyczne AMED
🇵🇱
Warszawa, Poland
First Moscow State Medical University n.a. Sechenov
🇷🇺
Moscow, Russian Federation
Office of Dr. Alma M. Cruz
🇵🇷
Carolina, Puerto Rico
GCM Medical Group PSC
🇵🇷
San Juan, Puerto Rico
GBUZ Clinical dermatology and venereological dispensary
🇷🇺
Krasnodar, Russian Federation
State scientific centre for dermatovenerology and cosmetolog
🇷🇺
Moscow, Russian Federation
SPb SBHI Skin-venerologic dispensary #10
🇷🇺
St. Petersburg, Russian Federation
Chang Gung Memorial Hospital - Kaohsiung
🇨🇳
Kaohsiung, Taiwan
National Taiwan University Hospital Hsin-Chu
🇨🇳
Hsinchu, Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳
Taoyuan Hsien, Taiwan
Arlington Dermatology
🇺🇸
Rolling Meadows, Illinois, United States
Oregon Medical Research Center
🇺🇸
Portland, Oregon, United States
Charité Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
Dermatology and Skin Surgery Center
🇺🇸
Exton, Pennsylvania, United States
Ajou University Hospital
🇰🇷
Suwon, Gyeonggi-do, Korea, Republic of
Chonnam National University Hospital
🇰🇷
Gwangju, Korea, Republic of
Ulsan University Hospital
🇰🇷
Ulsan, Korea, Korea, Republic of
National Taiwan University Hospital
🇨🇳
Taipei City, Zhongzheng District, Taiwan
Hospital de Jesus
🇲🇽
Mexico City, Distrito Federal, Mexico
Chung Shan Medical University Hospital
🇨🇳
Taichung City, Taiwan
Tokyo Medical University Hachioji Medical Center
🇯🇵
Hachioji, Tokyo, Japan
Gemeinschaftspraxis Mahlow
🇩🇪
Mahlow, Brandenburg, Germany
Taipei Medical University- Shuang Ho Hospital
🇨🇳
New Taipei City, Taiwan
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
DermMEDICA Sp. z o.o.
🇵🇱
Wroclaw, Poland
Lubelskie Centrum Diagnostyczne
🇵🇱
Swidnik, Poland
Centro Medico del Angel S.C.
🇲🇽
Mexicali, Baja California, Mexico