Plaque Psoriasis
Conditions
Brief summary
The main purpose of this study is to assess the safety and efficacy of LY4100511 in adult participants with moderate-to-severe plaque psoriasis.
Interventions
DRUGLY4100511
Administered orally
DRUGPlacebo
Administered orally
Sponsors
DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of plaque psoriasis for 6 months before the baseline day 1 randomization * Must have a body mass index (BMI) of 18 to 40 kilogram/square meter (kg/m2) (inclusive). * Must be willing to discontinue topical and/or systemic therapies for psoriasis before the first dose of study intervention. * Must agree to avoid prolonged exposure to the sun and to refrain from the use of tanning booths, sun lamps, and other sources of ultraviolet light during the study
Exclusion criteria
* Have had a clinically significant flare of psoriasis during the 12 weeks before the baseline, as assessed by the investigator. * Have a history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis. * Have any known or suspected diagnosis of inflammatory conditions other than psoriasis and psoriatic arthritis, including but not limited to rheumatoid arthritis, sarcoidosis, IBD (Crohn's disease or ulcerative colitis), or systemic lupus erythematosus. * Have a diagnosis of psoriatic arthritis requiring, or are currently receiving, systemic immunosuppressant medical treatment (including corticosteroids, immunosuppressants, and biologics). * Have a current or recent acute, active infection. Participant must have no symptoms or signs of confirmed or suspected infection and must have completed any appropriate anti-infective treatment for at least 30 days before screening and up to randomization/baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 (LY4100511 Versus Placebo) | Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 (LY4100511 200mg vs 400mg vs 800mg) | Week 12 | 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 an sPGA Score of 0 (Clear) or 1 (Almost Clear) With ≥2 Grade Improvement From Baseline at Week 12 | Week 12 | 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 Psoriasis Area and Severity Index (PASI-50) at Week 12 | Week 12 | 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 Psoriasis Area and Severity Index (PASI-75) at Week 12 | Week 12 | 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 Psoriasis Area and Severity Index (PASI-90) at Week 12 | Week 12 | 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 Psoriasis Area and Severity Index (PASI-100) at Week 12 | Week 12 | 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. |
| Change From Baseline in PASI Score at Week 12 | Baseline, Week 12 | 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. |
| Percent Change From Baseline in PASI Score at Week 12 | Baseline, Week 12 | 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. |
| Change From Baseline in the Percentage of Body Surface Area (BSA) Affected at Week 12 | Baseline, Week 12 | 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. |
| Percent Change From Baseline in the Percentage of BSA Affected at Week 12 | Baseline, Week 12 | 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. |
| Pharmacokinetics (PK): Steady State Maximum Concentration of LY4100511 (Cmax,ss) | Day 1: Predose, 0.5, 1 hours postdose; Day 15: Predose, 0.5, 1, 4 hours postdose; Day 57: Predose, 0.5, 1, 4 hours postdose | Steady State Maximum Concentration of LY4100511 (Cmax,ss) is reported. |
| Pharmacokinetics (PK): Steady State Trough Concentration (Ctrough,ss) of LY4100511 | Predose at Day 8, 15, 29, 57 and 85 | Ctrough,ss of LY4100511 |
| Number of Participants With TEAEs and SAEs Observed During the Study of LY4100511 | Baseline up to Week 12 | 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 |
Countries
Canada, Czechia, Germany, Hungary, Japan, Poland, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 12.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 179 Participants |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 54 | 0 / 56 | 0 / 56 |
| other Total, other adverse events | 28 / 55 | 23 / 54 | 30 / 56 | 29 / 56 |
| serious Total, serious adverse events | 0 / 55 | 0 / 54 | 1 / 56 | 0 / 56 |
Outcome results
None listed