Plaque Psoriasis
Conditions
Brief summary
This is an open-label, long-term safety study of roflumilast (ARQ-151) 0.3% cream in subjects with chronic plaque psoriasis involving up to 25% total Body Surface Area (BSA). Study medication will be applied by the qualifying subjects topically once daily for 52 weeks at home. Periodic clinic visits will include assessments for clinical safety, application site reactions, and disease improvement or progression.
Detailed description
Cohort 1 of this study consisted of participants who previously completed study ARQ-151-201 (NCT03638258), and Cohort 2 consisted of participants who were not previously enrolled in ARQ-151-201.
Interventions
DRUGRoflumilast
Roflumilast cream 0.3% for topical application
Sponsors
Arcutis Biotherapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Note: Subjects that consent to enter this open-label safety study have previously completed a companion study (ARQ-151-201 Phase 2 randomized controlled trial)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants legally competent to sign and give informed consent 2. Males and females ages 18 years and older 3. Subjects with chronic plaque psoriasis who met eligibility criteria for ARQ-151-201, successfully completed ARQ-151-201 through Week 12, and are able to enroll into this long-term safety study on the Week 12 visit of the previous study (ARQ-151-201). 4. Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at all study visits. In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial. Highly effective forms of contraception include: oral/implant/injectable/transdermal contraceptives, intrauterine device, or partner's vasectomy. If barrier methods are used (e.g., condom with spermicide, diaphragm with spermicide), then 2 forms of conception are required. The use of abstinence as a contraceptive measure is acceptable as long as this is a consistent part of a lifestyle choice and a backup method has been identified if the subject becomes sexually active. 5. Post-menopausal women with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization (permanent sterilization methods include hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy).
Exclusion criteria
1. Subjects who experienced an ARQ-151 treatment-related AE or a serious AE (SAE) that precluded further treatment with ARQ-151 cream in Study ARQ-151-201. 2. Subjects that use any Excluded Medications and Treatments 3. Current diagnosis of guttate, erythrodermic/exfoliative, palmoplantar, or pustular psoriasis. 4. Subjects who cannot discontinue the use of strong P-450 cytochrome inhibitors e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, suboxone and telithromycin during the study period. 5. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, and rifampin during the study period. 6. Known or suspected: * severe renal insufficiency or severe hepatic disorders * hypersensitivity to component(s) of the investigational products * history of severe depression, suicidal ideation 7. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. 8. 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. 9. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of study medication. 10. Current or a history of cancer within 5 years with the exception of fully treated skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 11. 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 Experiencing ≥1 Treatment-emergent Adverse Event (TEAE) | Up to 52 weeks | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AEs that began after initiating study treatment (treatment-emergent AEs \[TEAEs\]) in ARQ-151-202 are presented. |
| Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) | Up to 52 weeks | An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Weeks 12, 24, 36, and 52 | The number of participants with an IGA score of 0 ('clear') or 1 ('almost clear') at Week 12 is reported. 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 plaque severity. |
| Duration of Response in Participants Achieving 'Clear' IGA Score | Up to 52 weeks | The median time to re-starting study therapy among participants who achieve a 'clear' IGA score and stop treatment to all lesions is presented. |
| Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Weeks 12, 24, 36, and 52 | The number of participants who had intertriginous area involvement with an I-IGA score of 'clear' or 'almost clear' is presented. The I-IGA is 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater plaque severity. |
| Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Baseline and Weeks 12, 24, 36, and 52 | The number of participants achieving a 75% reduction in mPASI (eg, mPASI-75) score relative to baseline is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were recruited at 30 study sites in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Study 201 Participants This arm consisted of participants who previously participated in study ARQ-151-201 and received either roflumilast (ARQ-151) cream (0.15% or 0.3%) or vehicle cream, and agreed to enroll in the 202 study. Upon completing the 201 study, participants applied roflumilast cream 0.3% once daily for 52 weeks for long-term safety monitoring in the 202 study. | 230 |
| Cohort 2: Non-study 201 Participants This arm consisted of participants who did not previously participate in study ARQ-151-201, and were enrolled in the 202 study after the time of amendment 1. Participants applied roflumilast cream 0.3% once daily for 52 weeks for long-term safety monitoring. | 102 |
| Total | 332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | COVID-19 Disruption | 2 | 0 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Lost to Follow-up | 24 | 10 |
| Overall Study | Withdrawal by Subject | 26 | 10 |
Baseline characteristics
| Characteristic | Cohort 2: Non-study 201 Participants | Total | Cohort 1: Study 201 Participants |
|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 15.64 | 54.5 years STANDARD_DEVIATION 14.23 | 55.3 years STANDARD_DEVIATION 13.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 63 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 268 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Modified Psoriasis Area Severity Index (mPASI) | 4.50 score on a scale STANDARD_DEVIATION 3.821 | 5.14 score on a scale STANDARD_DEVIATION 3.755 | 5.42 score on a scale STANDARD_DEVIATION 3.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants | 19 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 29 Participants | 24 Participants |
| Race/Ethnicity, Customized Multiple/Other | 5 Participants | 15 Participants | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 85 Participants | 268 Participants | 183 Participants |
| Sex: Female, Male Female | 46 Participants | 150 Participants | 104 Participants |
| Sex: Female, Male Male | 56 Participants | 182 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 230 | 0 / 102 |
| other Total, other adverse events | 15 / 230 | 7 / 102 |
| serious Total, serious adverse events | 8 / 230 | 2 / 102 |
Outcome results
Primary
Number of Participants Experiencing ≥1 Serious Adverse Event (SAE)
An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Time frame: Up to 52 weeks
Population: All randomized participants who received ≥1 dose of study drug are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Study 201 Participants | Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) | 8 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) | 2 Participants |
Primary
Number of Participants Experiencing ≥1 Treatment-emergent Adverse Event (TEAE)
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. All AEs that began after initiating study treatment (treatment-emergent AEs \[TEAEs\]) in ARQ-151-202 are presented.
Time frame: Up to 52 weeks
Population: All randomized participants who received ≥1 dose of study treatment are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Study 201 Participants | Number of Participants Experiencing ≥1 Treatment-emergent Adverse Event (TEAE) | 104 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Experiencing ≥1 Treatment-emergent Adverse Event (TEAE) | 60 Participants |
Secondary
Duration of Response in Participants Achieving 'Clear' IGA Score
The median time to re-starting study therapy among participants who achieve a 'clear' IGA score and stop treatment to all lesions is presented.
Time frame: Up to 52 weeks
Population: All participants who received ≥1 dose of study drug and achieved an IGA score of 'clear' are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Study 201 Participants | Duration of Response in Participants Achieving 'Clear' IGA Score | 8.0 weeks |
| Cohort 2: Non-study 201 Participants | Duration of Response in Participants Achieving 'Clear' IGA Score | 12.4 weeks |
Secondary
Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75)
The number of participants achieving a 75% reduction in mPASI (eg, mPASI-75) score relative to baseline is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity.
Time frame: Baseline and Weeks 12, 24, 36, and 52
Population: All participants who received ≥1 dose of study drug and have data available at the relevant time points are included. This endpoint was added at protocol amendment 1, and thus mPASI was not assessed in a subset of participants in Cohort 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 12 | 67 Participants |
| Cohort 1: Study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 24 | 114 Participants |
| Cohort 1: Study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 36 | 130 Participants |
| Cohort 1: Study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 52 | 124 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 52 | 61 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 12 | 63 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 36 | 55 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants Achieving a 75% Reduction From Baseline in Modified Psoriasis Severity Index (mPASI-75) | Week 24 | 57 Participants |
Secondary
Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear'
The number of participants with an IGA score of 0 ('clear') or 1 ('almost clear') at Week 12 is reported. 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 plaque severity.
Time frame: Weeks 12, 24, 36, and 52
Population: All participants who received ≥1 dose of study drug and have data available at the relevant time points are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 12 | 92 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 24 | 79 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 36 | 68 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 52 | 68 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 52 | 39 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 12 | 47 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 36 | 36 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | Week 24 | 34 Participants |
Secondary
Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear'
The number of participants who had intertriginous area involvement with an I-IGA score of 'clear' or 'almost clear' is presented. The I-IGA is 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater plaque severity.
Time frame: Weeks 12, 24, 36, and 52
Population: All participants who received ≥1 dose of study drug, have intertriginous area involvement, and have data available at the relevant time points are included. This endpoint was added at protocol amendment 1, and thus I-IGA was not assessed in a subset of participants in Cohort 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 12 | 11 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 24 | 13 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 36 | 13 Participants |
| Cohort 1: Study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 52 | 9 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 52 | 10 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 12 | 15 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 36 | 10 Participants |
| Cohort 2: Non-study 201 Participants | Number of Participants With Intertriginous Area Involvement Achieving an Intertriginous Area Investigator Global Assessment (I-IGA) Score of Clear' or 'Almost Clear' | Week 24 | 14 Participants |