Trial Outcomes & Findings for Twin Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis (NCT NCT04211389)

NCT ID: NCT04211389

Last Updated: 2022-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

442 participants

Primary outcome timeframe

Week 8

Results posted on

2022-12-07

Participant Flow

Adult participants with chronic plaque psoriasis were enrolled at 43 study sites in the United States and Canada.

Participant milestones

Participant milestones
Measure
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.
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.
Overall Study
STARTED
290
152
Overall Study
COMPLETED
264
131
Overall Study
NOT COMPLETED
26
21

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
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.
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

Twin Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Roflumilast Cream 0.3%
n=290 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=152 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Total
n=442 Participants
Total of all reporting groups
Age, Continuous
46.9 years
STANDARD_DEVIATION 15.07 • n=5 Participants
47.1 years
STANDARD_DEVIATION 14.07 • n=7 Participants
47.0 years
STANDARD_DEVIATION 14.72 • n=5 Participants
Sex: Female, Male
Female
114 Participants
n=5 Participants
52 Participants
n=7 Participants
166 Participants
n=5 Participants
Sex: Female, Male
Male
176 Participants
n=5 Participants
100 Participants
n=7 Participants
276 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
76 Participants
n=5 Participants
50 Participants
n=7 Participants
126 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
213 Participants
n=5 Participants
102 Participants
n=7 Participants
315 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
American-Indian or Alaska Native
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
20 Participants
n=5 Participants
9 Participants
n=7 Participants
29 Participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
13 Participants
n=5 Participants
9 Participants
n=7 Participants
22 Participants
n=5 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race/Ethnicity, Customized
White
240 Participants
n=5 Participants
126 Participants
n=7 Participants
366 Participants
n=5 Participants
Race/Ethnicity, Customized
Not Reported
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
8 Participants
n=5 Participants
4 Participants
n=7 Participants
12 Participants
n=5 Participants
Race/Ethnicity, Customized
More than 1 Race
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Hispanic or Latino
76 Participants
n=5 Participants
50 Participants
n=7 Participants
126 Participants
n=5 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
213 Participants
n=5 Participants
102 Participants
n=7 Participants
315 Participants
n=5 Participants
Investigator Global Assessment (IGA) Scores at Baseline
0 - Clear
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Investigator Global Assessment (IGA) Scores at Baseline
1 - Almost Clear
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Investigator Global Assessment (IGA) Scores at Baseline
2 - Mild
50 Participants
n=5 Participants
24 Participants
n=7 Participants
74 Participants
n=5 Participants
Investigator Global Assessment (IGA) Scores at Baseline
3 - Moderate
220 Participants
n=5 Participants
118 Participants
n=7 Participants
338 Participants
n=5 Participants
Investigator Global Assessment (IGA) Scores at Baseline
4 - Severe
20 Participants
n=5 Participants
10 Participants
n=7 Participants
30 Participants
n=5 Participants
Psoriasis Area Severity Index (PASI) Score
6.5 score on a scale
STANDARD_DEVIATION 3.22 • n=5 Participants
7.0 score on a scale
STANDARD_DEVIATION 3.52 • n=7 Participants
6.7 score on a scale
STANDARD_DEVIATION 3.33 • n=5 Participants
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
5.8 units on a scale
STANDARD_DEVIATION 2.61 • n=5 Participants
6.1 units on a scale
STANDARD_DEVIATION 2.75 • n=7 Participants
5.9 units on a scale
STANDARD_DEVIATION 2.66 • n=5 Participants
Baseline Psoriasis Symptom Diary (PSD) Total Score
69.3 score on a scale
STANDARD_DEVIATION 40.66 • n=5 Participants
77.4 score on a scale
STANDARD_DEVIATION 41.24 • n=7 Participants
72.1 score on a scale
STANDARD_DEVIATION 41.00 • n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: All randomized participants with data are included.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=264 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=131 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving Success on the Investigator Global Assessment (IGA) Scale
99 Participants
9 Participants

SECONDARY outcome

Timeframe: From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 124 days)

Population: All randomized participants are included.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=290 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=152 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Time to Achieve Psoriasis Area Severity Index-50 (PASI-50)
30.0 days
Interval 29.0 to 42.0
NA days
Interval 71.0 to
Median number of days and upper bound of CI were not calculable due to low number of cases.

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: All randomized participants with data available are included.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=264 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=131 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving Psoriasis Area Severity Index-75 (PASI-75)
103 Participants
7 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: All randomized participants with data available are included.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=290 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=152 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90)
45 Participants
3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=47 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=27 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving Success in Intertriginous Investigator Global Assessment (I-IGA) Scale Assessment of Disease Severity at Week 8
32 Participants
5 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=47 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=27 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving I-IGA Score of 'Clear' at Week 8
27 Participants
2 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=215 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=109 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score
Week 2
90 Participants
23 Participants
Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score
Week 4
120 Participants
23 Participants
Number of Participants Achieving Success in Worst Itch Numerical Rating Scale (WI-NRS) Pruritus Score
Week 8
143 Participants
36 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 4 and 8

Population: All randomized participants are included.

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.

Outcome measures

Outcome measures
Measure
Roflumilast Cream 0.3%
n=290 Participants
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=152 Participants
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Change From Baseline in Psoriasis Symptoms Diary (PSD) Score
Week 4
-42.7 score on a scale
Interval -47.7 to -37.7
-16.7 score on a scale
Interval -22.8 to -10.6
Change From Baseline in Psoriasis Symptoms Diary (PSD) Score
Week 8
-49.3 score on a scale
Interval -54.8 to -43.7
-22.8 score on a scale
Interval -29.6 to -16.0

Adverse Events

Roflumilast Cream 0.3%

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Vehicle Cream

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Roflumilast Cream 0.3%
n=290 participants at risk
Participants applied roflumilast cream 0.3% QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Vehicle Cream
n=152 participants at risk
Participants applied inactive vehicle cream matched to roflumilast cream QD for 8 weeks. There was a 1-week follow-up period after completing treatment.
Nervous system disorders
Cervical radiculopathy
0.00%
0/290 • Up to 124 days
All participants who received ≥1 dose of study treatment are included.
0.66%
1/152 • Up to 124 days
All participants who received ≥1 dose of study treatment are included.

Other adverse events

Adverse event data not reported

Additional Information

Arcutis Medical Information

Arcutis Biotherapeutics

Phone: +1 (844) 692-6729

Results disclosure agreements

  • Principal investigator is a sponsor employee The Sponsor is supportive of publishing clinical trial findings. The process of coordinating publication efforts is detailed in the Clinical Trial Agreement.
  • Publication restrictions are in place

Restriction type: OTHER