Chronic Plaque Psoriasis
Conditions
Brief summary
This study will assess the safety and efficacy of ARQ-151 cream vs placebo applied once a day for 56 days by subjects with chronic plaque psoriasis
Detailed description
This is a parallel group, double blind, vehicle-controlled study in which ARQ-151 cream or vehicle is applied once daily x 8 weeks to subjects with psoriasis
Interventions
DRUGARQ-151 0.3% cream
ARQ-151 0.3% cream
ARQ-151 vehicle cream
Sponsors
Arcutis Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants legally competent to sign and give informed consented and if appropriate assent as required by local laws * Males and females ages 2 years and older (inclusive) * Clinical diagnosis of psoriasis vulgaris of at least 6 months duration (3 months for children) as determined by the Investigator * Females of childbearing potential (FOCBP) must have a negative pregnancy test at Screening (Visit 1) and Baseline (Visit 2). In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial. * In good health as judged by the Investigator, based on medical history, physical examination, serum chemistry labs, hematology values, and urinalysis. * Subjects considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator.
Exclusion criteria
* Planned excessive exposure of treated area(s) to either natural or artificial sunlight, tanning bed or other LED. * Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. * Previous treatment with ARQ-151 or its active ingredient * Subjects with any serious medical condition or laboratory abnormality that would prevent study participation or place the subject at significant risk, as determined by the Investigator. * Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of investigational product * Subjects who are unable to communicate, read or understand the local language, or who display another condition, which in the Investigator's opinion, makes them unsuitable for clinical study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Success on the Investigator Global Assessment (IGA) Scale | Week 8 | The number of participants achieving success in IGA assessment of disease severity at Week 8 is presented for each arm. Success was defined as achievement of an IGA score of 0 ('clear') or 1 ('almost clear') at Week 8, accompanied by a ≥2-grade improvement from baseline IGA score. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity. The IGA scores are based on observed data, whereas odds ratio and p-values were calculated using multiple imputation of missing values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 124 days) | The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The time to achieve PASI-50 (defined as a 50% reduction from baseline in PASI score) is presented, and is based on observed data only. Participants are included whether they achieved PASI-50 or not. |
| Number of Participants Achieving Psoriasis Area Severity Index-75 (PASI-75) | Baseline (Day 1) and Week 8 | The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The number of participants achieving PASI-75 (defined as a 75% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only. |
| Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90) | Baseline (Day 1) and Week 8 | The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The number of participants achieving PASI-90 (defined as a 90% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only. |
| Number of Participants Achieving Success in Intertriginous Investigator Global Assessment (I-IGA) Scale Assessment of Disease Severity at Week 8 | Week 8 | The number of participants with I-IGA score ≥2 at baseline achieving success in IGA assessment of disease severity at Week 8 is presented (observed data only) for each arm. Success was defined as achievement of an I-IGA score of 0 ('clear') or 1 ('almost clear') at Week 8, accompanied by a ≥2-grade improvement from baseline I-IGA score. The IGA is a 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity. |
| Number of Participants Achieving I-IGA Score of 'Clear' at Week 8 | Week 8 | The number of participants achieving an IGA score of 0 ('clear') at Week 8 is presented (observed data only) for each arm. The I-IGA is a 5-point scale assessing the severity of intertriginous area plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity. |
| Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Baseline (Day 1) and Week 2, Week 4, Week 8 | The number of participants achieving success in WI-NRS is presented. Success is defined as achievement of a ≥ 4-point reduction in WI-NRS pruritus score in participants with WI-NRS pruritus score ≥ 4 at baseline. The WI-NRS is a 10 point scale ranging from 0 ('no itch') to 10 ('worst itch imaginable') the participant experienced in the past 24 hours, with higher scores indicating greater symptoms severity. Results are based on observed data only. |
| Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Baseline (Day 1) and Weeks 4 and 8 | The PSD is a 16-item questionnaire asking subjects to rate the severity of psoriasis-related symptoms in the past 24 hours. Each question is scored from 0 (no symptoms) to 10 (worst imaginable symptoms). Scores range from 0 to 160, with higher scores indicating greater symptom severity. The least squares (LS) mean (95% CI) change in PSD total score relative to baseline is presented for each treatment arm, with decreases from baseline indicating symptom improvement. |
Countries
Canada, United States
Participant flow
Recruitment details
Adult participants with chronic plaque psoriasis were enrolled at 43 study sites in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Cream 0.3% Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment. | 290 |
| Vehicle Cream Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment. | 152 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 15 | 7 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 11 |
Baseline characteristics
| Characteristic | Roflumilast Cream 0.3% | Vehicle Cream | Total |
|---|---|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 15.07 | 47.1 years STANDARD_DEVIATION 14.07 | 47.0 years STANDARD_DEVIATION 14.72 |
| Baseline Psoriasis Symptom Diary (PSD) Total Score | 69.3 score on a scale STANDARD_DEVIATION 40.66 | 77.4 score on a scale STANDARD_DEVIATION 41.24 | 72.1 score on a scale STANDARD_DEVIATION 41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 76 Participants | 50 Participants | 126 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 213 Participants | 102 Participants | 315 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Investigator Global Assessment (IGA) Scores at Baseline 0 - Clear | 0 Participants | 0 Participants | 0 Participants |
| Investigator Global Assessment (IGA) Scores at Baseline 1 - Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Investigator Global Assessment (IGA) Scores at Baseline 2 - Mild | 50 Participants | 24 Participants | 74 Participants |
| Investigator Global Assessment (IGA) Scores at Baseline 3 - Moderate | 220 Participants | 118 Participants | 338 Participants |
| Investigator Global Assessment (IGA) Scores at Baseline 4 - Severe | 20 Participants | 10 Participants | 30 Participants |
| Psoriasis Area Severity Index (PASI) Score | 6.5 score on a scale STANDARD_DEVIATION 3.22 | 7.0 score on a scale STANDARD_DEVIATION 3.52 | 6.7 score on a scale STANDARD_DEVIATION 3.33 |
| Race/Ethnicity, Customized American-Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 20 Participants | 9 Participants | 29 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants | 9 Participants | 22 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 76 Participants | 50 Participants | 126 Participants |
| Race/Ethnicity, Customized More than 1 Race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 213 Participants | 102 Participants | 315 Participants |
| Race/Ethnicity, Customized Not Reported | 5 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 240 Participants | 126 Participants | 366 Participants |
| Sex: Female, Male Female | 114 Participants | 52 Participants | 166 Participants |
| Sex: Female, Male Male | 176 Participants | 100 Participants | 276 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score | 5.8 units on a scale STANDARD_DEVIATION 2.61 | 6.1 units on a scale STANDARD_DEVIATION 2.75 | 5.9 units on a scale STANDARD_DEVIATION 2.66 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 290 | 0 / 152 |
| other Total, other adverse events | 0 / 290 | 0 / 152 |
| serious Total, serious adverse events | 0 / 290 | 1 / 152 |
Outcome results
Primary
Number of Participants Achieving Success on the Investigator Global Assessment (IGA) Scale
The number of participants achieving success in IGA assessment of disease severity at Week 8 is presented for each arm. Success was defined as achievement of an IGA score of 0 ('clear') or 1 ('almost clear') at Week 8, accompanied by a ≥2-grade improvement from baseline IGA score. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity. The IGA scores are based on observed data, whereas odds ratio and p-values were calculated using multiple imputation of missing values.
Time frame: Week 8
Population: All randomized participants with data are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving Success on the Investigator Global Assessment (IGA) Scale | 99 Participants |
| Vehicle Cream | Number of Participants Achieving Success on the Investigator Global Assessment (IGA) Scale | 9 Participants |
Comparison: IGA Success at Week 8 Odds Ratiop-value: <0.000195% CI: [3.17, 13.7]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Psoriasis Symptoms Diary (PSD) Score
The PSD is a 16-item questionnaire asking subjects to rate the severity of psoriasis-related symptoms in the past 24 hours. Each question is scored from 0 (no symptoms) to 10 (worst imaginable symptoms). Scores range from 0 to 160, with higher scores indicating greater symptom severity. The least squares (LS) mean (95% CI) change in PSD total score relative to baseline is presented for each treatment arm, with decreases from baseline indicating symptom improvement.
Time frame: Baseline (Day 1) and Weeks 4 and 8
Population: All randomized participants are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roflumilast Cream 0.3% | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 4 | -42.7 score on a scale |
| Roflumilast Cream 0.3% | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 8 | -49.3 score on a scale |
| Vehicle Cream | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 4 | -16.7 score on a scale |
| Vehicle Cream | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 8 | -22.8 score on a scale |
Comparison: LS Mean Difference at Week 4p-value: <0.000195% CI: [-31.9, -20]ANCOVA
Comparison: LS Mean Difference at Week 8p-value: <0.000195% CI: [-33.2, -19.7]ANCOVA
Secondary
Number of Participants Achieving I-IGA Score of 'Clear' at Week 8
The number of participants achieving an IGA score of 0 ('clear') at Week 8 is presented (observed data only) for each arm. The I-IGA is a 5-point scale assessing the severity of intertriginous area plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity.
Time frame: Week 8
Population: All randomized participants with intertriginous area involvement and I-IGA score at Baseline ≥ 2 who have Week 8 data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving I-IGA Score of 'Clear' at Week 8 | 27 Participants |
| Vehicle Cream | Number of Participants Achieving I-IGA Score of 'Clear' at Week 8 | 2 Participants |
Comparison: I-IGA Clear at Week 8 Odds Ratiop-value: 0.000295% CI: [3.1, 75.35]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Psoriasis Area Severity Index-75 (PASI-75)
The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The number of participants achieving PASI-75 (defined as a 75% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only.
Time frame: Baseline (Day 1) and Week 8
Population: All randomized participants with data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving Psoriasis Area Severity Index-75 (PASI-75) | 103 Participants |
| Vehicle Cream | Number of Participants Achieving Psoriasis Area Severity Index-75 (PASI-75) | 7 Participants |
Comparison: PASI-75 at Week 8 Odds Ratiop-value: <0.000195% CI: [4.49, 24.19]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90)
The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The number of participants achieving PASI-90 (defined as a 90% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only.
Time frame: Baseline (Day 1) and Week 8
Population: All randomized participants with data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90) | 45 Participants |
| Vehicle Cream | Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90) | 3 Participants |
Comparison: PASI-90 at Week 8 Odds Ratiop-value: 0.000295% CI: [2.45, 28.86]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Success in Intertriginous Investigator Global Assessment (I-IGA) Scale Assessment of Disease Severity at Week 8
The number of participants with I-IGA score ≥2 at baseline achieving success in IGA assessment of disease severity at Week 8 is presented (observed data only) for each arm. Success was defined as achievement of an I-IGA score of 0 ('clear') or 1 ('almost clear') at Week 8, accompanied by a ≥2-grade improvement from baseline I-IGA score. The IGA is a 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity.
Time frame: Week 8
Population: All randomized participants with intertriginous area involvement and I-IGA score at Baseline ≥ 2 who have Week 8 data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving Success in Intertriginous Investigator Global Assessment (I-IGA) Scale Assessment of Disease Severity at Week 8 | 32 Participants |
| Vehicle Cream | Number of Participants Achieving Success in Intertriginous Investigator Global Assessment (I-IGA) Scale Assessment of Disease Severity at Week 8 | 5 Participants |
Comparison: I-IGA Success at Week 8 Odds Ratiop-value: 0.000495% CI: [2.33, 53.68]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score
The number of participants achieving success in WI-NRS is presented. Success is defined as achievement of a ≥ 4-point reduction in WI-NRS pruritus score in participants with WI-NRS pruritus score ≥ 4 at baseline. The WI-NRS is a 10 point scale ranging from 0 ('no itch') to 10 ('worst itch imaginable') the participant experienced in the past 24 hours, with higher scores indicating greater symptoms severity. Results are based on observed data only.
Time frame: Baseline (Day 1) and Week 2, Week 4, Week 8
Population: All randomized participants with WI-NRS pruritus score ≥4 at baseline and data available at the relevant time points are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roflumilast Cream 0.3% | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 2 | 90 Participants |
| Roflumilast Cream 0.3% | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 4 | 120 Participants |
| Roflumilast Cream 0.3% | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 8 | 143 Participants |
| Vehicle Cream | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 2 | 23 Participants |
| Vehicle Cream | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 4 | 23 Participants |
| Vehicle Cream | Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score | Week 8 | 36 Participants |
p-value: 0.002695% CI: [1.43, 4.58]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [2.65, 9.18]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [2.07, 6.23]Cochran-Mantel-Haenszel
Secondary
Time to Achieve Psoriasis Area Severity Index-50 (PASI-50)
The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The time to achieve PASI-50 (defined as a 50% reduction from baseline in PASI score) is presented, and is based on observed data only. Participants are included whether they achieved PASI-50 or not.
Time frame: From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 124 days)
Population: All randomized participants are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Roflumilast Cream 0.3% | Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | 30.0 days |
| Vehicle Cream | Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | NA days |
Comparison: Time to Achieve PASI-50p-value: <0.000195% CI: [3.029, 5.844]Log Rank