Psoriasis
Conditions
Keywords
Psoriasis, Plaque Psoriasis
Brief summary
This study assessed the safety and pharmacokinetics (PK) of a single dose application of ARQ-151 cream 0.5% to 25 cm\^2 of psoriatic plaque(s) (Cohort 1). The study also assessed the safety, PK and efficacy of ARQ-151 cream 0.5% vs vehicle and ARQ-151 cream 0.15% vs vehicle applied once a day for 28 days to individuals with 0.5% to 5.0% body surface area (BSA) of chronic plaque psoriasis (Cohort 2).
Detailed description
There were 2 cohorts of participants. Cohort 1 was a single dose study of ARQ-151 0.5% cream applied to 25 cm\^2 of psoriatic plaque(s) in 8 psoriasis participants. Cohort 2 was a parallel group, double blind, vehicle controlled study in which ARQ-151 cream 0.5%, ARQ-151 cream 0.15% or vehicle cream was applied once a day for 28 days to participants with between 0.5% to 5.0% BSA of chronic plaque psoriasis. Participants were adult (≥18 years old) males or females with chronic plaque psoriasis.
Interventions
DRUGARQ-151 cream 0.5%
0.5% active concentration
0.15% active concentration
Vehicle cream
Sponsors
Arcutis Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Cohort 1 was open label. Cohort 2 was double blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult male and female participants aged ≥18 years. * In Cohort 1, participants must have at least 25 cm\^2 of chronic plaque psoriasis (excluding the face, scalp, intertriginous areas, palms and soles). * In Cohort 2, participants must have 0.5% to 5.0% of total BSA of chronic plaque psoriasis and at least one target plaque, of at least 9 cm\^2 in size with a TPSS ≥4 (excluding the face, scalp, intertriginous areas, palms and soles). * Women of childbearing potential must have a negative urine pregnancy test at Screening and agree to use birth control throughout the trial. * In good health as judged by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry labs, hematology values, and urinalysis. * Participants agree not to have prolonged sun exposure during the course of the study. Tanning bed use is not allowed. * Participants are competent to sign and give informed consent and considered reliable and capable of adhering to the Protocol and visit schedule.
Exclusion criteria
* Participants with non-plaque forms of psoriasis (erythrodermic, guttate, pustular or palmo-plantar psoriasis) or with drug-induced psoriasis. * Evidence of skin conditions other than psoriasis that would interfere with evaluation of the effect of the study medication. * Pregnant or lactating women or women planning to become pregnant during the study and / or within 28 days following the last dose of study medication. * Known allergies to excipients in ARQ-151 cream. * Participants who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors for two weeks prior to the baseline visit and during the study period. * Participants who are unwilling to refrain from using a tanning bed for 2 weeks before and during the study. * Participants who cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis. * Participants with a history of chronic alcohol or drug abuse in past 6 months. * History of and/or concurrent condition of serious hypersensitivity (anaphylactic shock or anaphylactoid reaction) to phosphodiesterase type 4 (PDE-4) inhibitors. * Current or a history of cancer within 5 years with the exception of fully excised skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. * Participants with active infection that requires oral or intravenous administration of antibiotics, antifungal or antiviral agents. * Participants who are unable to communicate, read or understand language, or who display another condition which makes them unsuitable for clinical study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Baseline and Week 4 | Difference in least squares mean percent change from baseline at Week 4 in the product of target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Baseline and Weeks 1, 2 and 3 | Difference in least squares mean percent change from baseline at Weeks 1, 2 and 3 in target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement. |
| Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Baseline and Weeks 1, 2, 3, and 4 | Difference in least squares mean percent change from baseline at Weeks 1, 2, 3 and 4 in total plaque severity score (TPSS) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. A negative percent change indicates improvement. |
| Percent Change From Baseline in Target Plaque Area in Cohort 2 | Baseline and Weeks 1, 2, 3, and 4 | Difference in least squares mean percent change from baseline at Weeks 1, 2, 3, and 4 in target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPA score as a covariate. Target plaque area (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted in 7 centers in Canada and 1 center in the United States (US). There was a total of 91 unique participants; 6 participants who completed Cohort 1 also participated in Cohort 2, with 2 per treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - ARQ-151 Cream 0.5% Single-dose application of ARQ-151 cream 0.5% to 25 cm\^2 of psoriatic plaque(s) | 8 |
| Cohort 2 - ARQ-151 Cream 0.5% ARQ-151 cream 0.5% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA | 28 |
| Cohort 2 - ARQ-151 Cream 0.15% ARQ-151 cream 0.15% applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA | 26 |
| Cohort 2 - ARQ-151 Vehicle Cream Vehicle cream applied daily for 28 days to all psoriatic plaques, not exceeding an application area of 5% BSA | 29 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 2: Cohort 2 | Lost to Follow-up | 0 | 1 | 1 | 1 |
| Period 2: Cohort 2 | Other | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1 - ARQ-151 Cream 0.5% | Cohort 2 - ARQ-151 Cream 0.5% | Cohort 2 - ARQ-151 Cream 0.15% | Cohort 2 - ARQ-151 Vehicle Cream |
|---|---|---|---|---|---|
| Age, Continuous | 50.80 Years STANDARD_DEVIATION 14.75 | 51.6 Years STANDARD_DEVIATION 16.92 | 50.8 Years STANDARD_DEVIATION 15.76 | 54.8 Years STANDARD_DEVIATION 13.5 | 47.0 Years STANDARD_DEVIATION 13.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 8 Participants | 27 Participants | 26 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 0 Participants | 2 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 73 Participants | 8 Participants | 23 Participants | 22 Participants | 20 Participants |
| Sex: Female, Male Female | 38 Participants | 7 Participants | 12 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 53 Participants | 1 Participants | 16 Participants | 19 Participants | 17 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 / 8 | 0 / 30 | 0 / 28 | 0 / 31 |
| other Total, other adverse events | 1 / 8 | 9 / 30 | 5 / 28 | 11 / 31 |
| serious Total, serious adverse events | 0 / 8 | 0 / 30 | 0 / 28 | 0 / 31 |
Outcome results
Primary
Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2
Difference in least squares mean percent change from baseline at Week 4 in the product of target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.
Time frame: Baseline and Week 4
Population: The modified intent-to-treat (mITT) population included all participants who were in the safety population for Cohort 2 with at least 1 postbaseline efficacy evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | -66.6 Percent change | Standard Error 7.27 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | -66.0 Percent change | Standard Error 7.61 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in 4 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | -38.1 Percent change | Standard Error 7.34 |
Comparison: LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000795% CI: [-44.6, -12.4]Mixed Models Analysis
Comparison: LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.001195% CI: [-44.2, -11.5]Mixed Models Analysis
Secondary
Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2
Difference in least squares mean percent change from baseline at Weeks 1, 2 and 3 in target plaque severity score (TPSS) x target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS x TPA score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. TPA (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.
Time frame: Baseline and Weeks 1, 2 and 3
Population: The mITT population included all participants who were in the safety population for Cohort 2 with at least 1 postbaseline efficacy evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 2 | -48.7 Percent change | Standard Error 6.4 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 1 | -34.7 Percent change | Standard Error 5.79 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 3 | -61.5 Percent change | Standard Error 6.69 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 2 | -50.1 Percent change | Standard Error 6.75 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 1 | -36.4 Percent change | Standard Error 6.16 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 3 | -55.6 Percent change | Standard Error 7.03 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 1 | -31.5 Percent change | Standard Error 5.99 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 3 | -32.6 Percent change | Standard Error 6.81 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in 1, 2, 3 Week Target Plaque Severity Score x Target Plaque Area in Cohort 2 | Week 2 | -30.4 Percent change | Standard Error 6.55 |
Comparison: At Week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.549395% CI: [-13.7, 7.3]Mixed Models Analysis
Comparison: At week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.36595% CI: [-15.7, 5.9]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.006495% CI: [-31.3, -5.3]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.003995% CI: [-33, -6.5]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000195% CI: [-42.9, -14.8]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.001995% CI: [-37.3, -8.7]Mixed Models Analysis
Secondary
Percent Change From Baseline in Target Plaque Area in Cohort 2
Difference in least squares mean percent change from baseline at Weeks 1, 2, 3, and 4 in target plaque area (TPA) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPA score as a covariate. Target plaque area (cm\^2) was determined by multiplying the longest diameter (cm) of the target plaque by the widest perpendicular diameter (cm) (perpendicular to the longest diameter of the target plaque). A negative percent change indicates improvement.
Time frame: Baseline and Weeks 1, 2, 3, and 4
Population: The mITT population included all participants who were in the safety population for Cohort 2 with at least 1 postbaseline efficacy evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 1 | -9.15 Percent change | Standard Error 2.981 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 2 | -14.95 Percent change | Standard Error 4.211 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 3 | -22.63 Percent change | Standard Error 4.666 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 4 | -31.87 Percent change | Standard Error 6.014 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 4 | -28.28 Percent change | Standard Error 6.228 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 1 | -8.22 Percent change | Standard Error 3.198 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 3 | -17.00 Percent change | Standard Error 4.844 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 2 | -16.19 Percent change | Standard Error 4.407 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 4 | -11.61 Percent change | Standard Error 5.938 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 2 | -10.37 Percent change | Standard Error 4.225 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 3 | -9.95 Percent change | Standard Error 4.636 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Target Plaque Area in Cohort 2 | Week 1 | -11.82 Percent change | Standard Error 3.089 |
Comparison: At Week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.320995% CI: [-2.65, 7.99]Mixed Models Analysis
Comparison: At Week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.194795% CI: [-1.88, 9.08]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.356195% CI: [-14.4, 5.24]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.24995% CI: [-15.79, 4.16]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.027695% CI: [-23.992, -1.44]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.222395% CI: [-18.44, 4.36]Mixed Models Analysis
Comparison: At Week 4; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.010895% CI: [-35.72, -4.82]Mixed Models Analysis
Comparison: At Week 4; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.037295% CI: [-32.34, -1.01]Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Plaque Severity Score in Cohort 2
Difference in least squares mean percent change from baseline at Weeks 1, 2, 3 and 4 in total plaque severity score (TPSS) between each dose concentration level of ARQ-151 cream and vehicle using mixed model repeated measures (MMRM) analysis with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects and baseline TPSS score as a covariate. For TPSS, all target lesions were scored individually for signs of induration, scaling, and erythema using a 5-point severity scale: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. A negative percent change indicates improvement.
Time frame: Baseline and Weeks 1, 2, 3, and 4
Population: The mITT population included all participants who were in the safety population for Cohort 2 with at least 1 postbaseline efficacy evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 1 | -30.5 Percent change | Standard Error 4.96 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 2 | -41.9 Percent change | Standard Error 5.01 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 3 | -51.5 Percent change | Standard Error 5.46 |
| Cohort 2 - ARQ-151 Cream 0.5% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 4 | -55.1 Percent change | Standard Error 5.41 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 4 | -58.2 Percent change | Standard Error 5.56 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 1 | -34.3 Percent change | Standard Error 5.2 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 3 | -52.0 Percent change | Standard Error 5.63 |
| Cohort 2 - ARQ-151 Cream 0.15% | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 2 | -45.6 Percent change | Standard Error 5.22 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 4 | -36.5 Percent change | Standard Error 5.5 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 2 | -26.4 Percent change | Standard Error 5.19 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 3 | -30.1 Percent change | Standard Error 5.56 |
| Cohort 2 - ARQ-151 Vehicle Cream | Percent Change From Baseline in Total Plaque Severity Score in Cohort 2 | Week 1 | -26.2 Percent change | Standard Error 5.16 |
Comparison: At Week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.362695% CI: [-13.6, 5]Mixed Models Analysis
Comparison: At Week 1; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.101195% CI: [-17.8, 1.6]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.001795% CI: [-25.1, -6]Mixed Models Analysis
Comparison: At Week 2; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000295% CI: [-29.1, -9.4]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000395% CI: [-32.4, -10.2]Mixed Models Analysis
Comparison: At Week 3; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000395% CI: [-33.2, -10.4]Mixed Models Analysis
Comparison: At Week 4; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.00195% CI: [-29.5, -7.8]Mixed Models Analysis
Comparison: At Week 4; LS mean difference from vehicle; Estimates for LS means and accompanying 95% confidence intervals and P values are from a mixed model for repeated measures (MMRM) with center within country, treatment, study visit, and treatment-by-study visit interaction as fixed effects, and baseline value as a covariate.p-value: 0.000295% CI: [-32.9, -10.6]Mixed Models Analysis