Trial Outcomes & Findings for A Study of LY4100511 (DC-853) in Adult Participants With Moderate-to-Severe Plaque Psoriasis (NCT NCT06602219)

A Study of LY4100511 (DC-853) in Adult Participants With Moderate-to-Severe Plaque Psoriasis

Percentage of participants achieving ≥75% reduction from baseline in PASI-75 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Percentage of participants achieving ≥75% reduction from baseline in PASI-75 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Percentage of participants achieving a static Physician's Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at Week 12. The investigator assessed psoriasis severity on a 5-point scale from 0 (clear) to 4 (severe): * 0 = Clear: No signs of psoriasis; post-inflammatory hyperpigmentation may occur * 1 = Almost clear: Normal to pink lesions; no thickening; no or minimal focal scaling * 2 = Mild: Pink to light red color; slight thickening; mainly fine scaling * 3 = Moderate: Dull bright red erythema; moderate thickening; moderate scaling * 4 = Severe: Bright to deep red; severe thickening with hard edges; coarse scaling covering most or all lesions

Percentage of participants achieving ≥50% reduction from baseline in PASI-50 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Percentage of participants achieving ≥75% reduction from baseline in PASI-75 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Percentage of participants achieving ≥90% reduction from baseline in PASI-90 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Percentage of participants achieving ≥100% reduction from baseline in PASI-100 at Week 12 without use of background antipsoriasis therapy were responders. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Least square mean was determined with mixed model repeated measures (MMRM) using an unstructured covariance matrix, including treatment, visit, treatment-by-visit interaction, baseline PASI score, prior biologic therapy (Yes/No), and geographic region as fixed effects. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Least square mean was determined with mixed model repeated measures (MMRM) using an unstructured covariance matrix, including treatment, visit, treatment-by-visit interaction, baseline PASI score, prior biologic therapy (Yes/No), and geographic region as fixed effects. The PASI measures psoriasis severity based on lesion characteristics and body surface area (BSA) affected. Erythema, thickness, and scaling are each scored from 0 (none) to 4 (very severe) across four regions: head, trunk, upper limbs, and lower limbs. Area involvement in each region is graded from 0 (none) to 6 (90-100%). The sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region and a region-specific BSA weight (0.1, 0.3, 0.2, 0.4). Regional scores are summed to give a total PASI score ranging from 0 to 72, with higher values indicating greater severity.

Least square mean was determined with MMRM using an unstructured covariance matrix, including treatment, visit, treatment-by-visit interaction, baseline BSA, prior biologic therapy (Yes/No), geographic region, and baseline BMI, baseline is the last non-missing pre-dose value. BSA is a measurement of the affected skin area. It was defined as the percentage of surface area of the body involved with the condition being assessed, (that is, plaque psoriasis). 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.

Least square mean was determined with MMRM using an unstructured covariance matrix, including treatment, visit, treatment-by-visit interaction, baseline BSA, prior biologic therapy (Yes/No), geographic region, and baseline BMI, baseline is the last non-missing pre-dose value. BSA is a measurement of the affected skin area. It was defined as the percentage of surface area of the body involved with the condition being assessed, (that is, plaque psoriasis). 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.

Steady State Maximum Concentration of LY4100511 (Cmax,ss) is reported.

Ctrough,ss of LY4100511

The number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) observed during the study of LY4100511. A TEAE is defined as an AE that occurs during or after the first study drug administration and up to and including the follow-up visit. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: * Results in death * Is life-threatening (risk of death at the time of the event) * Requires inpatient hospitalization or prolongation of existing hospitalization (excluding elective admission for a stable pre-existing condition) * Results in persistent disability/incapacity * Is a congenital anomaly/birth defect * Other medically important event that may jeopardize the participant or require intervention to prevent the above outcomes