Chronic Plaque Psoriasis
Conditions
Brief summary
This is a double-blind, parallel group, vehicle-controlled study to assess the safety and efficacy of roflumilast (ARQ-151) 0.3% cream vs vehicle (placebo) cream for treatment of chronic plaque psoriasis (CPP) in adult participants with 2 to 20% body surface area (BSA) of CPP.
Interventions
DRUGRoflumilast 0.3% cream
Roflumilast 0.3% cream for topical application.
DRUGVehicle Cream
Vehicle cream for topical application.
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 consent 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 in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8 | Baseline (Day 1) and Week 8 | The number of participants 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 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 0 (no disease) to 72 (maximal disease) \[higher scores indicate greater symptom severity\]. 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 Intertriginous IGA (I-IGA) Success at Week 8 | Baseline (Day 1) and Week 8 | The number of participants achieving I-IGA success at Week 8 is presented. Success is defined as achievement of I-IGA score of 0 ('clear') or 1 ('almost clear') at Week 8 PLUS a ≥2-grade improvement in score from Baseline. The I-IGA is a 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater symptom severity. Participant counts are based on observed data only. |
| 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 = 121 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. |
| Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Baseline (Day 1) and Weeks 2, 4, and 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'), with higher scores indicating greater symptoms severity. Results are based on observed data only. |
| Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | 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. |
| Number of Participants Achieving Score of 'Clear' in I-IGA 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 plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'); higher scores indicate greater symptom severity. |
Countries
Canada, United States
Participant flow
Recruitment details
Adult male and female participants with chronic plaque psoriasis involving between 2% and 20% body surface area (BSA) \[excluding the scalp, palms, and soles\] were recruited at 43 study sites in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| Rofumilast Cream 0.3% Participants apply roflumilast cream 0.3% topically once daily for 8 weeks. | 286 |
| Vehicle Cream Participants apply vehicle cream topically once daily for 8 weeks. | 153 |
| Total | 439 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Lost to Follow-up | 12 | 4 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 11 |
Baseline characteristics
| Characteristic | Vehicle Cream | Rofumilast Cream 0.3% | Total |
|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 15.77 | 47.6 years STANDARD_DEVIATION 14.09 | 48.0 years STANDARD_DEVIATION 14.69 |
| Baseline Psoriasis Symptom Diary (PSD) Total Baseline Score | 73.4 score on a scale STANDARD_DEVIATION 41.29 | 72.1 score on a scale STANDARD_DEVIATION 42.75 | 72.6 score on a scale STANDARD_DEVIATION 42.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 63 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants | 223 Participants | 342 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score 0 - Clear | 0 Participants | 0 Participants | 0 Participants |
| Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score 1 - Almost Clear | 1 Participants | 5 Participants | 6 Participants |
| Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score 2 - Mild | 16 Participants | 33 Participants | 49 Participants |
| Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score 3 - Moderate | 16 Participants | 27 Participants | 43 Participants |
| Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score 4 - Severe | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 21 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 8 Participants | 16 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 15 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 124 Participants | 234 Participants | 358 Participants |
| Sex: Female, Male Female | 57 Participants | 97 Participants | 154 Participants |
| Sex: Female, Male Male | 96 Participants | 189 Participants | 285 Participants |
| Whole Body Investigator Global Assessment (IGA) Baseline Score 0 - Clear | 0 Participants | 0 Participants | 0 Participants |
| Whole Body Investigator Global Assessment (IGA) Baseline Score 1 - Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Whole Body Investigator Global Assessment (IGA) Baseline Score 2 - Mild | 20 Participants | 51 Participants | 71 Participants |
| Whole Body Investigator Global Assessment (IGA) Baseline Score 3 - Moderate | 122 Participants | 206 Participants | 328 Participants |
| Whole Body Investigator Global Assessment (IGA) Baseline Score 4 - Severe | 11 Participants | 29 Participants | 40 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 0 | 12 Participants | 16 Participants | 28 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 1 | 5 Participants | 11 Participants | 16 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 10 | 6 Participants | 20 Participants | 26 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 2 | 11 Participants | 14 Participants | 25 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 3 | 10 Participants | 26 Participants | 36 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 4 | 7 Participants | 26 Participants | 33 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 5 | 14 Participants | 32 Participants | 46 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 6 | 26 Participants | 37 Participants | 63 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 7 | 20 Participants | 34 Participants | 54 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 8 | 23 Participants | 49 Participants | 72 Participants |
| Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score 9 | 19 Participants | 20 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 286 | 0 / 153 |
| other Total, other adverse events | 0 / 286 | 0 / 153 |
| serious Total, serious adverse events | 2 / 286 | 1 / 153 |
Outcome results
Primary
Number of Participants Achieving Success in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8
The number of participants 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 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 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: Baseline (Day 1) and Week 8
Population: All randomized participants with data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Success in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8 | 108 Participants |
| Vehicle Cream | Number of Participants Achieving Success in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8 | 8 Participants |
Comparison: IGA Success Odds Ratiop-value: <0.000195% CI: [7.58, 56.48]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: Weeks 4 and 8
Population: All randomized participants are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rofumilast Cream 0.3% | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 4 | -43.5 score on a scale |
| Rofumilast Cream 0.3% | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 8 | -50.1 score on a scale |
| Vehicle Cream | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 4 | -17.7 score on a scale |
| Vehicle Cream | Change From Baseline in Psoriasis Symptoms Diary (PSD) Score | Week 8 | -19.2 score on a scale |
Comparison: Comparison of change from baseline in PSD score at Week 4p-value: <0.000195% CI: [-31.7, -20]ANCOVA
Comparison: Comparison of change from baseline in PSD score at Week 8p-value: <0.000195% CI: [-37.2, -24.6]ANCOVA
Secondary
Number of Participants Achieving Intertriginous IGA (I-IGA) Success at Week 8
The number of participants achieving I-IGA success at Week 8 is presented. Success is defined as achievement of I-IGA score of 0 ('clear') or 1 ('almost clear') at Week 8 PLUS a ≥2-grade improvement in score from Baseline. The I-IGA is a 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater symptom severity. Participant counts are based on observed data only.
Time frame: Baseline (Day 1) and Week 8
Population: All randomized participants with intertriginous area involvement an I-IGA score at Baseline ≥ 2 and who have Week 8 data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Intertriginous IGA (I-IGA) Success at Week 8 | 37 Participants |
| Vehicle Cream | Number of Participants Achieving Intertriginous IGA (I-IGA) Success at Week 8 | 4 Participants |
Comparison: I-IGA Success at Week 8 Odds Ratiop-value: <0.000195% CI: [2.33, 138.2]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 at Week 8 are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Psoriasis Area Severity Index 75 (PASI-75) | 106 Participants |
| Vehicle Cream | Number of Participants Achieving Psoriasis Area Severity Index 75 (PASI-75) | 10 Participants |
Comparison: PASI-75 at Week 8 Odds Ratiop-value: <0.000195% CI: [5.15, 27.93]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90)
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 0 (no disease) to 72 (maximal disease) \[higher scores indicate greater symptom severity\]. 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 at Week 8 are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90) | 57 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: <0.000195% CI: [4.38, 73.09]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Score of 'Clear' in I-IGA 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 plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'); higher scores indicate greater symptom severity.
Time frame: Week 8
Population: All randomized participants with intertriginous area involvement an I-IGA score at Baseline ≥ 2 and who have Week 8 data available are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Score of 'Clear' in I-IGA at Week 8 | 33 Participants |
| Vehicle Cream | Number of Participants Achieving Score of 'Clear' in I-IGA at Week 8 | 3 Participants |
Comparison: I-IGA Clear at Week 8 Odds Ratiop-value: 0.00395% CI: [2.99, 288.36]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success
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'), with higher scores indicating greater symptoms severity. Results are based on observed data only.
Time frame: Baseline (Day 1) and Weeks 2, 4, and 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) |
|---|---|---|---|
| Rofumilast Cream 0.3% | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 2 Observed Data | 73 Participants |
| Rofumilast Cream 0.3% | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 4 Observed Data | 101 Participants |
| Rofumilast Cream 0.3% | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 8 Observed Data | 129 Participants |
| Vehicle Cream | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 2 Observed Data | 24 Participants |
| Vehicle Cream | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 4 Observed Data | 18 Participants |
| Vehicle Cream | Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | Week 8 Observed Data | 26 Participants |
Comparison: WI-NRS Success at Week 2 Odds Ratiop-value: 0.119795% CI: [0.98, 3.19]Cochran-Mantel-Haenszel
Comparison: WI-NRS Success at Week 4 Odds Ratiop-value: <0.000195% CI: [2.31, 8.26]Cochran-Mantel-Haenszel
Comparison: WI-NRS at Week 8 Odds Ratiop-value: <0.000195% CI: [3.85, 15.94]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.
Time frame: From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 121 days)
Population: All randomized participants are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rofumilast Cream 0.3% | Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | 31.0 days |
| Vehicle Cream | Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | 104.0 days |
Comparison: Time to PASI-50p-value: <0.000195% CI: [2.795, 5.351]Log Rank