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

Psoriasis Clinical Trial

— OASIS-1  

Official title:

A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03482011
• Other study ID #: 16505
• Secondary ID: I6T-MC-AMAK2017-
• Status: Completed
• Phase: Phase 3
• Start date: April 24, 2018
• Est. completion date: January 16, 2020

Study information

• Verified date: February 1, 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 530
• Est. completion date: January 16, 2020
• Est. primary completion date: March 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Mirikizumab
Administered SC
• Placebo
Administered SC

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Static Physician's Global Assessment of (sPGA) (0,1) With at Least a 2-point Improvement From Baseline	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.	Week 16
Primary	Percentage of Participants Achieving a =90% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 90)	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).	Week 16
Secondary	Percentage of Participants Achieving a =75% Improvement From Baseline in PASI (PASI 75)	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).	Week 4
Secondary	Percentage of Participants Achieving a =75% Improvement From Baseline in PASI (PASI 75)	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).	Week 16
Secondary	Percentage of Participants Achieving a =100% Improvement From Baseline in Psoriasis Area and Severity Score (PASI 100)	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).	Week 16
Secondary	Percentage of Participants With =1% of Body Surface Area (BSA) With Psoriasis Involvement	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.	Week 16
Secondary	Percentage of Participants With a Psoriasis Symptoms Scale (PSS) Symptoms Score of 0 in Those With a PSS Symptoms Score =1 at Baseline	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.	Week 16
Secondary	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	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.	Week 16
Secondary	Percentage of Participants Maintaining Clinical Response (PASI 90) After Re-randomization at the Start of the Randomized Withdrawal Period	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).	Week 52
Secondary	Change in Palmoplantar Psoriasis Severity Index (PPASI) Total Score in Participants With Palmoplantar Involvement at Baseline	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.	Week 16
Secondary	Change in Psoriasis Scalp Severity Index (PSSI) Total Score in Participants With Scalp Involvement at Baseline	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.	Week 16
Secondary	Change in Nail Psoriasis Severity Index (NAPSI) Total Score in Participants With Fingernail Involvement at Baseline	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.	Week 16
Secondary	Change From Baseline on the Short Form (SF)-36 Physical Component Summary (PCS)	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.	Baseline, Week 16
Secondary	Change From Baseline on the SF-36 Mental Component Summary (MCS)	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.	Baseline, Week 16
Secondary	Percentage of Participants With Patient's Global Assessment of Psoriasis (PatGA (0,1)) and >=2 Improvement From Baseline	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.	Baseline, Week 16
Secondary	Change From Baseline on the Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI-PSO)	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.	Baseline, Week 16
Secondary	Change From Baseline in Quick Inventory of Depressive Symptomology (QIDS-SR16) Total Score in Those With a Baseline QIDS-SR16 Total Score =11	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.	Baseline, Week 16
Secondary	Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) (0,1)	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.	Week 16
Secondary	Induction Period: Pharmacokinetics (PK): Minimum Observed Serum Concentration at Steady State (Ctrough,ss) of Mirikizumab at Week 16	Minimum observed serum concentration at steady state (Ctrough,ss) of mirikizumab at Week 16.	Week 16: Day 113