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

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.

Time frame: Week 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the Full analysis set (FAS).

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the SAS. Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the SAS. Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the SAS. Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the SAS. Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the SAS. Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Over the 16-week Treatment Period and the 4-week Follow-up Period (up to Week 20)

Population: All randomized participants who received at least 1 dose of study drug were included in the Safety Analysis Set (SAS). Analyses in the SAS were based on the study treatment received by each participant.

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.

Time frame: Baseline, 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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. 1. = Almost clear: Normal to pink coloration of lesions; no thickening; no to minimal focal scaling. 2. = 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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, number analyzed signifies participants who were evaluable at specified time points.

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.

Time frame: Baseline, Week 1, 2, 4, 8, 12 and 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Here, Number analyzed signifies participants who were evaluable at specified time points.

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.

Time frame: Baseline to Week 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

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.

Time frame: Baseline to Week 16

Population: All participants who had been randomized, received at least 1 dose of the study drug and had at least 1 evaluable postbaseline time point were included in the FAS.

Ctrough of study drug was determined from the plasma samples using a validated analytical method.

Time frame: Pre-dose at Week 1, 4, 8 and 16

Population: The PK analysis set consisted of all participants who were correctly administered at least 1 ME3183 dose and where ME3183 concentration data is available without any protocol deviation interfering with these results. Analyses in PK analysis set was based on the study treatment actually received by each participant. Here, number of participants analyzed= participants who were evaluable for this outcome measure. Number analyzed= participants who were evaluable at specified time points.