Trial Outcomes & Findings for Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis (NCT NCT04211363)

NCT ID: NCT04211363

Last Updated: 2022-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

439 participants

Primary outcome timeframe

Baseline (Day 1) and Week 8

Results posted on

2022-12-07

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Rofumilast Cream 0.3%
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
Participants apply vehicle cream topically once daily for 8 weeks.
Overall Study
STARTED
286
153
Overall Study
COMPLETED
255
133
Overall Study
NOT COMPLETED
31
20

Reasons for withdrawal

Reasons for withdrawal
Measure
Rofumilast Cream 0.3%
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
Participants apply vehicle cream topically once daily for 8 weeks.
Overall Study
Adverse Event
5
2
Overall Study
Physician Decision
0
1
Overall Study
Protocol Violation
1
0
Overall Study
Pregnancy
1
0
Overall Study
Lost to Follow-up
12
4
Overall Study
Withdrawal by Subject
11
11
Overall Study
Other
1
2

Baseline Characteristics

Baseline I-IGA assessment was added in protocol amendment 1.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Rofumilast Cream 0.3%
n=286 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=153 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Total
n=439 Participants
Total of all reporting groups
Age, Continuous
47.6 years
STANDARD_DEVIATION 14.09 • n=286 Participants
48.7 years
STANDARD_DEVIATION 15.77 • n=153 Participants
48.0 years
STANDARD_DEVIATION 14.69 • n=439 Participants
Sex: Female, Male
Female
97 Participants
n=286 Participants
57 Participants
n=153 Participants
154 Participants
n=439 Participants
Sex: Female, Male
Male
189 Participants
n=286 Participants
96 Participants
n=153 Participants
285 Participants
n=439 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
63 Participants
n=286 Participants
34 Participants
n=153 Participants
97 Participants
n=439 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
223 Participants
n=286 Participants
119 Participants
n=153 Participants
342 Participants
n=439 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=286 Participants
0 Participants
n=153 Participants
0 Participants
n=439 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
4 Participants
n=286 Participants
1 Participants
n=153 Participants
5 Participants
n=439 Participants
Race/Ethnicity, Customized
Asian
21 Participants
n=286 Participants
11 Participants
n=153 Participants
32 Participants
n=439 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
2 Participants
n=286 Participants
0 Participants
n=153 Participants
2 Participants
n=439 Participants
Race/Ethnicity, Customized
Black or African American
8 Participants
n=286 Participants
8 Participants
n=153 Participants
16 Participants
n=439 Participants
Race/Ethnicity, Customized
White
234 Participants
n=286 Participants
124 Participants
n=153 Participants
358 Participants
n=439 Participants
Race/Ethnicity, Customized
More than one race
2 Participants
n=286 Participants
1 Participants
n=153 Participants
3 Participants
n=439 Participants
Race/Ethnicity, Customized
Other
15 Participants
n=286 Participants
8 Participants
n=153 Participants
23 Participants
n=439 Participants
Whole Body Investigator Global Assessment (IGA) Baseline Score
0 - Clear
0 Participants
n=286 Participants
0 Participants
n=153 Participants
0 Participants
n=439 Participants
Whole Body Investigator Global Assessment (IGA) Baseline Score
1 - Almost Clear
0 Participants
n=286 Participants
0 Participants
n=153 Participants
0 Participants
n=439 Participants
Whole Body Investigator Global Assessment (IGA) Baseline Score
2 - Mild
51 Participants
n=286 Participants
20 Participants
n=153 Participants
71 Participants
n=439 Participants
Whole Body Investigator Global Assessment (IGA) Baseline Score
3 - Moderate
206 Participants
n=286 Participants
122 Participants
n=153 Participants
328 Participants
n=439 Participants
Whole Body Investigator Global Assessment (IGA) Baseline Score
4 - Severe
29 Participants
n=286 Participants
11 Participants
n=153 Participants
40 Participants
n=439 Participants
Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score
0 - Clear
0 Participants
n=68 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
0 Participants
n=33 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
0 Participants
n=101 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score
1 - Almost Clear
5 Participants
n=68 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
1 Participants
n=33 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
6 Participants
n=101 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score
2 - Mild
33 Participants
n=68 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
16 Participants
n=33 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
49 Participants
n=101 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score
3 - Moderate
27 Participants
n=68 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
16 Participants
n=33 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
43 Participants
n=101 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
Intertriginous Area Investigator Global Assessment (I-IGA) Baseline Score
4 - Severe
3 Participants
n=68 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
0 Participants
n=33 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
3 Participants
n=101 Participants • Baseline I-IGA assessment was added in protocol amendment 1.
Baseline Psoriasis Symptom Diary (PSD) Total Baseline Score
72.1 score on a scale
STANDARD_DEVIATION 42.75 • n=282 Participants • All participants with baseline PSD total scores available are included.
73.4 score on a scale
STANDARD_DEVIATION 41.29 • n=150 Participants • All participants with baseline PSD total scores available are included.
72.6 score on a scale
STANDARD_DEVIATION 42.21 • n=432 Participants • All participants with baseline PSD total scores available are included.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
0
16 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
12 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
28 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
1
11 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
5 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
16 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
2
14 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
11 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
25 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
3
26 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
10 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
36 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
4
26 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
7 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
33 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
5
32 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
14 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
46 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
6
37 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
26 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
63 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
7
34 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
20 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
54 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
8
49 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
23 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
72 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
9
20 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
19 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
39 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
Worst Itch Numerical Rating Scale (WI-NRS) Baseline Score
10
20 Participants
n=285 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
6 Participants
n=153 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.
26 Participants
n=438 Participants • One participant in the Roflumilast Cream 0.3% arm did not have a baseline WI-NRS assessment.

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: All randomized participants with data available are included.

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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=255 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=132 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Success in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8
108 Participants
8 Participants

SECONDARY outcome

Timeframe: From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 121 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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=286 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=153 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Time to Achieve Psoriasis Area Severity Index-50 (PASI-50)
31.0 days
Interval 29.0 to 41.0
104.0 days
Interval 85.0 to
Upper bound of 95% CI was not estimable due to low number of cases.

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: All randomized participants with data available at Week 8 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
Rofumilast Cream 0.3%
n=255 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=132 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Psoriasis Area Severity Index 75 (PASI-75)
106 Participants
10 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 8

Population: All randomized participants with data available at Week 8 are included.

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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=255 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=132 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90)
57 Participants
3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=52 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=29 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Intertriginous IGA (I-IGA) Success at Week 8
37 Participants
4 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=52 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=29 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Score of 'Clear' in I-IGA at Week 8
33 Participants
3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Rofumilast Cream 0.3%
n=218 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=115 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success
Week 2 Observed Data
73 Participants
24 Participants
Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success
Week 4 Observed Data
101 Participants
18 Participants
Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success
Week 8 Observed Data
129 Participants
26 Participants

SECONDARY outcome

Timeframe: 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
Rofumilast Cream 0.3%
n=286 Participants
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=153 Participants
Participants apply vehicle cream topically once daily for 8 weeks.
Change From Baseline in Psoriasis Symptoms Diary (PSD) Score
Week 8
-50.1 score on a scale
Interval -55.0 to -45.1
-19.2 score on a scale
Interval -25.3 to -13.0
Change From Baseline in Psoriasis Symptoms Diary (PSD) Score
Week 4
-43.5 score on a scale
Interval -48.2 to -38.9
-17.7 score on a scale
Interval -23.5 to -11.9

Adverse Events

Rofumilast Cream 0.3%

Serious events: 2 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
Rofumilast Cream 0.3%
n=286 participants at risk
Participants apply roflumilast cream 0.3% topically once daily for 8 weeks.
Vehicle Cream
n=153 participants at risk
Participants apply vehicle cream topically once daily for 8 weeks.
Injury, poisoning and procedural complications
Concussion
0.35%
1/286 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
0.00%
0/153 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
Injury, poisoning and procedural complications
Foot fracture
0.35%
1/286 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
0.00%
0/153 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
Musculoskeletal and connective tissue disorders
Deformity thorax
0.35%
1/286 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
0.00%
0/153 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma
0.00%
0/286 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
0.65%
1/153 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
Respiratory, thoracic and mediastinal disorders
Pneumothorax
0.35%
1/286 • Up to 121 days
All participants who received ≥1 dose of study drug are included.
0.00%
0/153 • Up to 121 days
All participants who received ≥1 dose of study drug 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