Efficacy and Safety of ME3183 in Subjects With Moderate to Severe Plaque Psoriasis

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Assess the Efficacy and Safety of ME3183 Administered Orally in Subjects With Moderate to Severe Plaque Psoriasis

The purpose of this study is to assess the efficacy and safety of ME3183 administered orally for moderate to severe plaque psoriasis in adults.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: ME3183

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5J 3S9
      • Laser Rejuvenation Clinics Edmonton D.T. Inc
  • Ontario
    • Cobourg, Ontario, Canada, K9A 0Z4
      • Skin Health
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Dermatrials Research Inc.
    • London, Ontario, Canada, N6H 5L5
      • DermEffects
    • Markham, Ontario, Canada, L3P 1X3
      • Lynderm Research Inc.
    • Mississauga, Ontario, Canada, L4Y 4C5
      • DermEdge Research
    • Ottawa, Ontario, Canada, K2C 3N2
      • Dermatology Ottawa Research Centre
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • The Centre for Dermatology
    • Sudbury, Ontario, Canada, P3A 1W8
      • Sudbury Skin Clinique
    • Toronto, Ontario, Canada, M3H 5Y8
      • Toronto Research Centre
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
  • Quebec
    • Montreal, Quebec, Canada, H3H 1V4
      • Dr. David Gratton Dermatologue Inc.
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 2C1
      • Skinsense Medical Research
• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Colorado
    • Denver, Colorado, United States, 80210
      • Colorado Medical Research Center, Inc.
  • Florida
    • Miami, Florida, United States, 33144
      • International Dermatology Research, INC
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Qualmedica Research, LLC
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Owensboro Dermatology Associates
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Shondra L. Smith, MD Dermatology & Advanced Aesthetics
  • New York
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc.
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Texas
    • Cypress, Texas, United States, 77433
      • Studies in Dermatology, LLC
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment and Research Center
    • Houston, Texas, United States, 77004
      • Center for Clinical Studies LTD, LLP
    • San Antonio, Texas, United States, 78229
      • Dermatology Clinical Research Center of San Antonio
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female, ages 18 to 75 years
• Participant with stable moderate to severe chronic plaque psoriasis of at least 24 weeks duration.

Exclusion Criteria:

• Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.
• Active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at Screening.
• Hepatitis B surface antigen positive at Screening.
• History of HIV or Positive for the HIV antibodies at Screening.
• History of allergy to any component of the study treatment.
• Active tuberculosis (TB) or a history of incompletely treated TB.
• Active infection (bacteria, viral, fungal, etc.) requiring treatment with systemic antibiotics within 4 weeks of Screening.
• Malignancy or history of malignancy except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia or carcinoma in situ of the cervix with no evidence of recurrence.
• Pregnant or breast feeding
• Received ustekinumab, secukinumab, brodalumab, ixekizumab, guselkumab, risankizumab, tildrakizumab, or briakinumab within 24 weeks of first administration of study treatment.
• Received TNF-α inhibitor(s)/blocker(s) within 8 weeks of first administration of study treatment.
• Received rituximab within 24 weeks of first administration of study treatment.
• Received phototherapy or any systemic medications/treatments within 4 weeks of the first administration of study treatment.

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ME3183 Dose 1, BID; Specified dose of ME3183 capsule for 16 weeks	Drug: ME3183; ME3183 capsule
Experimental: ME3183 Dose 2, QD; Specified dose of ME3183 capsule for 16 weeks	Drug: ME3183; ME3183 capsule
Experimental: ME3183 Dose 3, BID; Specified dose of ME3183 capsule for 16 weeks	Drug: ME3183; ME3183 capsule
Experimental: ME3183 Dose 4, QD; Specified dose of ME3183 capsule for 16 weeks	Drug: ME3183; ME3183 capsule
Placebo Comparator: Placebo; Placebo capsule of ME3183 for 16 weeks	Drug: Placebo; Placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Greater Than or Equal to (>=) 75% Reduction From Baseline in Psoriasis Area Severity Index (PASI) Score (PASI-75) at Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI score. The final PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Missing PASI at Week 16 are imputed as non-responders via NRI.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over the 16-week Treatment Period and the 4-week Follow-up Period	An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening, worsens during the study, regardless of the suspected cause of the event. A Treatment-Emergent Adverse Event (TEAE) is an AE that occurred during the study after the first dose of study drug or that was present prior to dosing and exacerbates after the first dose of study drug.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Number of Participants With Serious TEAEs Over the 16-week Treatment Period and the 4-week Follow-up Period	An SAE is any untoward medical occurrence, in the view of either the investigator or Sponsor, that: results in death,; is life-threatening,; results in inpatient hospitalization or prolongation of existing hospitalization,; results in persistent or significant disability/incapacity, and/or; is a congenital anomaly/birth defect. Other important medical events that may not be immediately life-threatening or result in death or hospitalization, based upon appropriate medical judgement, are considered SAEs if they are thought to jeopardize the subject and/or require medical or surgical intervention to prevent one of the outcomes defining an SAE.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Number of Participants With TEAEs by Severity Over the 16-week Treatment Period and the 4-week Follow-up Period	An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening, worsens during the study, regardless of the suspected cause of the event. AEs were classified by severity as follows: MILD: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with everyday activities. MODERATE: An event that is sufficiently discomforting to interfere with normal everyday activities. SEVERE: An event that prevents normal everyday activities.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Number of Participants With Clinically Significant Abnormalities in Physical Examination	Physical Examination included height and body mass index. Any change in Physical examination abnormalities that were deemed clinically significant by the investigator were recorded as TEAEs.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Vital signs parameters included blood pressure, heart rate, respiratory rate, body temperature, and body weight. Any change in vital sign abnormalities that were deemed clinically significant by the investigator were recorded as TEAEs.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Tests	Clinical laboratory testing included electrocardiogram (ECG), hematology, coagulation, blood chemistry, and urinalysis. Any change in clinical laboratory abnormalities that were deemed clinically significant by the investigator were recorded as TEAEs.	Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)
Percent Change From Baseline in PASI Score at All Visits From Week 1 to Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). Total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by degree of involvement for each anatomic region and then multiplied by constant. Scores for each anatomic region are combined to yield final PASI score (0 to 72). Higher scores= greater disease severity. Negative change from baseline indicates an improvement of disease symptoms. Percent reduction= (PASI score at Baseline - score at a follow-up visit) / PASI score at Baseline * 100.	Baseline, Week 1, 2, 4, 8, 12 and 16
Percentage of Participants Achieving >=50% Reduction From Baseline in the PASI Score (PASI-50) at All Visits From Week 1 to Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI score. The final PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Missing PASI at Week 16 are imputed as non-responders via NRI.	Baseline, Week 1, 2, 4, 8, 12 and 16
Percentage of Participants Achieving >=75% Reduction From Baseline in the PASI Score (PASI-75) at All Visits From Week 1 to Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI score. The final PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Missing PASI at Week 16 are imputed as non-responders via NRI.	Baseline, Week 1, 2, 4, 8, 12 and 16
Percentage of Participants Achieving >=90% Reduction From Baseline in the PASI Score (PASI-90) at All Visits From Week 1 to Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI score. The final PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Missing PASI at Week 16 are imputed as non-responders via NRI.	Baseline, Week 1, 2, 4, 8, 12 and 16
Percentage of Participants Achieving 100% Reduction From Baseline in the PASI Score (PASI-100) at All Visits From Week 1 to Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, induration, and desquamation) and percentage of affected skin surface area on defined anatomical regions. Erythema, induration/thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by degree of involvement for each anatomic region and then multiplied by a constant. The scores for each anatomic region are combined to yield the final PASI score. The final PASI score ranges from 0 to 72, with higher scores reflecting greater disease severity. Missing PASI at Week 16 are imputed as non-responders via NRI.	Baseline, 1, 2, 4, 8, 12 and 16
Time to PASI-50	Time to the first response of PASI-50 was defined as the number of days from the first dose of the study drug to the first response.	Baseline to Week 16
Time to PASI-75	Time to the first response of PASI-75 was defined as the number of days from the first dose of the study drug to the first response.	Baseline to Week 16
Percentage of Participants Achieving a Static Physicians Global Assessment (sPGA) Score of "0" ("Clear") or "1" ("Almost Clear") Combined With 2-point Reduction on the 5-point sPGA Scale at All Visits From Week 1 to Week 16	The Percentage of participants who achieved the static Physician's Global Assessment (sPGA) score of 'clear' or 'almost clear' (sPGA score 0 or 1) combined with 2-point reduction on the 5-point sPGA scale were reported. The investigator rated the severity of participant's psoriasis on the 5-point scale ranging from 0 (clear) to 4 (severe). 0 = Clear: No signs of psoriasis. Post-inflammatory hyperpigmentation may be present.; = Almost clear: Normal to pink coloration of lesions; no thickening; no to minimal focal scaling.; = Mild: Pink to light red coloration; just detectable to mild thickening; predominantly fine scaling. 3= Moderate: Dull bright red, clearly distinguishable erythema; clearly distinguishable to moderate thickening; moderate scaling. 4 = Severe: Bright to deep dark red coloration; severe thickening with hard edges; severe/coarse scaling covering almost all or all lesions. Missing values are imputed as non-responders via NRI.	Baseline, Week 1, 2, 4, 8, 12 and 16
Change From Baseline in Affected Body Surface Area (BSA) at All Visits From Week 1 to Week 16	BSA is a measurement of the affected skin area. The overall BSA affected by psoriasis plaques is estimated based on the palm area of the participant hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total BSA. Negative change from baseline indicates improvement.	Baseline, Week 1, 2, 4, 8, 12 and 16
Change From Baseline in the Itch Numerical Rating Scale (NRS) at All Visits From Week 1 to Week 16	The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." The overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. Negative change from baseline indicates improvement.	Baseline, Week 1, 2, 4, 8, 12 and 16
Change From Baseline in the Dermatology Life Quality Index (DLQI) Score at All Visits From Week 1 to Week 16	DLQI is a 10-item questionnaire that measures the impact of skin disease on a participant's quality of life over the last week. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI a total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on the quality of life of participants. Negative change from baseline indicates improvement.	Baseline, Week 1, 2, 4, 8, 12 and 16
Percentage of Participants With at Least a 5-point Reduction From Baseline in the DLQI Score at All Visits From Week 1 to Week 16	DLQI is a 10-item questionnaire that measures the impact of skin disease on a participant's quality of life over the last week. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI a total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on the quality of life of participants.	Baseline, Week 1, 2, 4, 8, 12 and 16
Trough Serum Concentration (Ctrough) of ME3183	Ctrough of study drug was determined from the plasma samples using a validated analytical method.	Pre-dose at Week 1, 4, 8 and 16

Collaborators and Investigators

• Sponsor: Meiji Pharma USA Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ME3183-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No