Plaque Psoriasis
Conditions
Brief summary
The main purpose of this study is to determine the efficacy and safety of LY3972406 in adult participants with moderate-to-severe plaque psoriasis.
Interventions
DRUGLY3972406
Administered orally
DRUGPlacebo
Administered orally
Sponsors
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Have moderate-to-severe chronic plaque psoriasis for at least 6 months prior to baseline * Have venous access sufficient to allow for blood sampling * Are able to swallow oral medication
Exclusion criteria
* Have any other skin conditions, excluding plaque psoriasis * Have a current or recent acute, active infection * Have manifestations of other autoimmune diseases, such as systemic lupus erythematosus. * Are lactating or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) | Week 12 | * The PASI is an investigator-administered, multi-item scale used to measure the severity of psoriasis based on lesion severity and the percent of body surface area (BSA) affected. * Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomical regions: head, trunk, upper limbs, 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 sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percent BSA (0.1, 0.3, 0.2, and 0.4 for the above 4 regions, respectively). The resultant score for each anatomic region is then summed to yield the final PASI score. It ranges from 0 to 72, with higher scores reflecting greater disease severity. * The nonresponder imputation (NRI) method was used to handle missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Body Surface Area (BSA) | Baseline, Week 12 | The percent BSA is the total percentage of psoriasis involvement on the participant's body surface, ranging from 0% (no involvement) to 100% (full involvement). It is measured using the handprint method, where 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The number of handprints fitting into the affected areas across the body is summed to estimate the total percentage of involvement. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) | Baseline, Week 12 | The DLQI is a validated, dermatology-specific, patient-reported outcomes 10-item questionnaire that evaluates participants health-related quality of life over the past week. The 10 questions are grouped into 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories and corresponding scores are: * Very much = 3 * A lot = 2 * A little = 1 * Not at all = 0 * Not relevant = 0. The total score is calculated by summing all 10 question responses and has a range of 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). |
| Pharmacokinetics (PK): Observed Trough Plasma Concentration of LY3972406 | Predose at Week 12 | Observed trough plasma concentration (Ctrough) of LY3972406. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY3972406 Participants received an oral dose of LY3972406 for 12 weeks. | 16 |
| Placebo Participants received an oral dose of placebo for 12 weeks. | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Assigned treatment by mistake | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol deviation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 9 |
Baseline characteristics
| Characteristic | LY3972406 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 13.3 | 50.3 years STANDARD_DEVIATION 13.2 | 50.2 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 23 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 23 Participants | 11 Participants |
| Region of Enrollment United States | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 15 Participants | 29 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 9 / 16 | 6 / 17 |
| serious Total, serious adverse events | 0 / 16 | 1 / 17 |
Outcome results
Primary
Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75)
* The PASI is an investigator-administered, multi-item scale used to measure the severity of psoriasis based on lesion severity and the percent of body surface area (BSA) affected. * Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomical regions: head, trunk, upper limbs, 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 sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percent BSA (0.1, 0.3, 0.2, and 0.4 for the above 4 regions, respectively). The resultant score for each anatomic region is then summed to yield the final PASI score. It ranges from 0 to 72, with higher scores reflecting greater disease severity. * The nonresponder imputation (NRI) method was used to handle missing data.
Time frame: Week 12
Population: All randomized participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY3972406 | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) | 18.8 percentage of participants |
| Placebo | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) | 5.9 percentage of participants |
p-value: 0.31695% CI: [0.3, 40.4]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI)
The DLQI is a validated, dermatology-specific, patient-reported outcomes 10-item questionnaire that evaluates participants health-related quality of life over the past week. The 10 questions are grouped into 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories and corresponding scores are: * Very much = 3 * A lot = 2 * A little = 1 * Not at all = 0 * Not relevant = 0. The total score is calculated by summing all 10 question responses and has a range of 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life).
Time frame: Baseline, Week 12
Population: All randomized participants who received at least one dose of the study drug and had non-missing values for this outcome at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY3972406 | Change From Baseline in Dermatology Life Quality Index (DLQI) | -6.71 score on a scale | Standard Error 1.64 |
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) | -4.35 score on a scale | Standard Error 1.54 |
p-value: 0.31195% CI: [-7.06, 2.35]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Percent Body Surface Area (BSA)
The percent BSA is the total percentage of psoriasis involvement on the participant's body surface, ranging from 0% (no involvement) to 100% (full involvement). It is measured using the handprint method, where 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The number of handprints fitting into the affected areas across the body is summed to estimate the total percentage of involvement.
Time frame: Baseline, Week 12
Population: All randomized participants who received at least one dose of the study drug and had non-missing values for this outcome at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY3972406 | Change From Baseline in Percent Body Surface Area (BSA) | -7.26 percent BSA | Standard Error 3.35 |
| Placebo | Change From Baseline in Percent Body Surface Area (BSA) | -0.48 percent BSA | Standard Error 3.19 |
p-value: 0.17595% CI: [-17.15, 3.6]Mixed Model Repeated Measures Analysis
Secondary
Pharmacokinetics (PK): Observed Trough Plasma Concentration of LY3972406
Observed trough plasma concentration (Ctrough) of LY3972406.
Time frame: Predose at Week 12
Population: All randomized participants who received at least one dose of the study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY3972406 | Pharmacokinetics (PK): Observed Trough Plasma Concentration of LY3972406 | 158 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 155 |