Trial Outcomes & Findings for An Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Genital Psoriasis (NCT NCT03777436)
NCT ID: NCT03777436
Last Updated: 2024-05-14
Results Overview
The modified sPGA-G is the assessment by the Investigator of the participant's psoriasis lesions' overall disease severity in the genital area at the time of evaluation. The modified sPGA-G is a 5-point scale ranging from clear (0), almost clear (1), mild (2), moderate (3), to severe (4), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, plaque elevation, and scaling. A modified sPGA-G response is defined as modified sPGA-G score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16. Missing values were imputed using the multiple imputation (MI) method. Two-sided 95% confidence intervals (CIs) for the within-group proportions were based on the Wilson-score method.
COMPLETED
PHASE3
289 participants
Baseline and Week 16 of the Placebo-controlled Phase
2024-05-14
Participant Flow
Participants were enrolled at 49 centers in Belgium, Canada, France, Germany, Italy, and the United States from February 2019 to February 2022.
Participants were randomized in a 1:1 ratio to receive either apremilast or matched placebo for the first 16 weeks (Placebo-controlled Phase) of the study. At Week 16, eligible participants may have continued on active treatment by entering a 16-week extension phase (Apremilast Extension Phase). Total treatment duration = 32 weeks.
Participant milestones
| Measure |
Placebo-controlled Phase: Placebo
Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Apremilast Extension Phase: Apremilast 30 mg
Eligible participants who completed the Placebo-controlled Phase entered the Apremilast Extension Phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
|
|---|---|---|---|
|
Placebo-controlled Phase
STARTED
|
146
|
143
|
0
|
|
Placebo-controlled Phase
Took at Least 1 Dose of Investigational Product (IP)
|
145
|
143
|
0
|
|
Placebo-controlled Phase
COMPLETED
|
111
|
119
|
0
|
|
Placebo-controlled Phase
NOT COMPLETED
|
35
|
24
|
0
|
|
Apremilast Extension Phase
STARTED
|
0
|
0
|
229
|
|
Apremilast Extension Phase
Took at Least 1 Dose of IP
|
0
|
0
|
228
|
|
Apremilast Extension Phase
COMPLETED
|
0
|
0
|
201
|
|
Apremilast Extension Phase
NOT COMPLETED
|
0
|
0
|
28
|
Reasons for withdrawal
| Measure |
Placebo-controlled Phase: Placebo
Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Apremilast Extension Phase: Apremilast 30 mg
Eligible participants who completed the Placebo-controlled Phase entered the Apremilast Extension Phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
|
|---|---|---|---|
|
Placebo-controlled Phase
Adverse Event
|
8
|
10
|
0
|
|
Placebo-controlled Phase
Lack of Efficacy
|
0
|
1
|
0
|
|
Placebo-controlled Phase
Withdrawal by Subject
|
19
|
3
|
0
|
|
Placebo-controlled Phase
Non-compliance with study drug
|
0
|
2
|
0
|
|
Placebo-controlled Phase
Lost to Follow-up
|
7
|
7
|
0
|
|
Placebo-controlled Phase
Physician Decision
|
0
|
1
|
0
|
|
Placebo-controlled Phase
Due to COVID-19 control measures
|
1
|
0
|
0
|
|
Apremilast Extension Phase
Adverse Event
|
0
|
0
|
6
|
|
Apremilast Extension Phase
Lack of Efficacy
|
0
|
0
|
1
|
|
Apremilast Extension Phase
Withdrawal by Subject
|
0
|
0
|
13
|
|
Apremilast Extension Phase
Lost to Follow-up
|
0
|
0
|
7
|
|
Apremilast Extension Phase
Miscellaneous
|
0
|
0
|
1
|
Baseline Characteristics
An Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Genital Psoriasis
Baseline characteristics by cohort
| Measure |
Placebo-controlled Phase: Placebo
n=146 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=143 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Total
n=289 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.4 Years
STANDARD_DEVIATION 14.38 • n=5 Participants
|
43.5 Years
STANDARD_DEVIATION 13.36 • n=7 Participants
|
45.0 Years
STANDARD_DEVIATION 13.93 • n=5 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
102 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
13 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
131 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
256 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
131 Participants
n=5 Participants
|
131 Participants
n=7 Participants
|
262 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Modified Static Physician Global Assessment of Genitalia (sPGA-G) Score
3 (Moderate)
|
128 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
251 Participants
n=5 Participants
|
|
Modified Static Physician Global Assessment of Genitalia (sPGA-G) Score
4 (Severe)
|
18 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 16 of the Placebo-controlled PhasePopulation: The ITT analysis set consisted of all participants who are randomized regardless of whether the participant received IP.
The modified sPGA-G is the assessment by the Investigator of the participant's psoriasis lesions' overall disease severity in the genital area at the time of evaluation. The modified sPGA-G is a 5-point scale ranging from clear (0), almost clear (1), mild (2), moderate (3), to severe (4), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, plaque elevation, and scaling. A modified sPGA-G response is defined as modified sPGA-G score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16. Missing values were imputed using the multiple imputation (MI) method. Two-sided 95% confidence intervals (CIs) for the within-group proportions were based on the Wilson-score method.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=146 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=143 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Percentage of Participants With a Modified sPGA-G Response at Week 16
|
19.5 Percentage of participants
Interval 12.7 to 26.3
|
39.6 Percentage of participants
Interval 31.2 to 48.0
|
SECONDARY outcome
Timeframe: Baseline and Week 16 of the placebo-controlled phasePopulation: The ITT analysis set consisted of all participants who are randomized regardless of whether the participant received IP.
The sPGA is the assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 3 (moderate) to 4 (severe), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation. An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16. Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=146 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=143 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16
|
6.9 Percentage of participants
Interval 2.7 to 11.2
|
22.2 Percentage of participants
Interval 15.0 to 29.3
|
SECONDARY outcome
Timeframe: Baseline and Week 16 of the placebo-controlled phasePopulation: ITT analysis set with Baseline GPI-NRS score ≥ 4.
The GPI-NRS is a self-reported measure where participants were asked to assess their psoriasis symptoms in the genital area and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A GPI-NRS response is defined as ≥ 4 point reduction (improvement) from Baseline. Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=121 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=122 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16
|
19.6 Percentage of participants
Interval 11.9 to 27.4
|
47.3 Percentage of participants
Interval 37.9 to 56.6
|
SECONDARY outcome
Timeframe: Baseline and Week 16 of the placebo-controlled phasePopulation: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total BSA). A negative change from Baseline indicates a reduction of affected BSA. Based on mixed-effect model for repeated measures (MMRM) model.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=111 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=120 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Change From Baseline in Affected Body Surface Area (BSA) at Week 16
|
-0.79 Change in percentage of affected BSA
Standard Error 0.669
|
-4.12 Change in percentage of affected BSA
Standard Error 0.664
|
SECONDARY outcome
Timeframe: Baseline and Week 16 of the placebo-controlled phasePopulation: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot). Total scores have a possible range of 0-30, where 0 represents the best score, and 30 represents the worst health-related quality of life. A negative change from Baseline indicates an improvement in health-related quality of life scores.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=107 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=117 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
|
-2.6 Scores on a scale
Standard Error 0.57
|
-5.3 Scores on a scale
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Baseline and Week 16 of the placebo-controlled phasePopulation: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
The GPSS is a self-reported measure where participants were asked to assess each of their psoriasis symptoms (itch, pain, discomfort, stinging, burning, redness, scaling, and cracking) in the genital area and select a number on a scale of 0-10, where 0 represents no symptoms, and 10 represents the worst imaginable. Results from each symptom assessment were summed to generate a total GPSS score ranging from 0 (no genital psoriasis symptoms) to 80 (worst imaginable genital psoriasis symptoms). A negative change from Baseline indicates an improvement in genital psoriasis symptoms.
Outcome measures
| Measure |
Placebo-controlled Phase: Placebo
n=107 Participants
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=116 Participants
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
|---|---|---|
|
Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score at Week 16
|
-5.3 Score on a scale
Standard Error 1.85
|
-20.5 Score on a scale
Standard Error 1.83
|
Adverse Events
Placebo-controlled Phase: Placebo
Placebo-controlled Phase: Apremilast 30 mg
Apremilast Extension Phase: Apremilast 30 mg
Serious adverse events
| Measure |
Placebo-controlled Phase: Placebo
n=145 participants at risk
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=143 participants at risk
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Apremilast Extension Phase: Apremilast 30 mg
n=229 participants at risk
Eligible participants who completed the Placebo-controlled Phase entered the Apremilast Extension Phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
|
|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.44%
1/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Infections and infestations
Clostridium difficile infection
|
0.69%
1/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Infections and infestations
Gastroenteritis
|
0.69%
1/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.70%
1/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Infections and infestations
Urinary tract infection
|
0.69%
1/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.69%
1/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.70%
1/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.69%
1/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.44%
1/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.70%
1/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
0.00%
0/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
Other adverse events
| Measure |
Placebo-controlled Phase: Placebo
n=145 participants at risk
Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Placebo-controlled Phase: Apremilast 30 mg
n=143 participants at risk
Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
|
Apremilast Extension Phase: Apremilast 30 mg
n=229 participants at risk
Eligible participants who completed the Placebo-controlled Phase entered the Apremilast Extension Phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
12/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
25.9%
37/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
11.8%
27/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Gastrointestinal disorders
Nausea
|
7.6%
11/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
22.4%
32/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
7.4%
17/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Infections and infestations
Nasopharyngitis
|
8.3%
12/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
8.4%
12/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
4.8%
11/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
|
Nervous system disorders
Headache
|
11.0%
16/145 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
23.1%
33/143 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
6.6%
15/229 • Up to a maximum of 41.4 weeks
The safety analysis set consisted of all participants who were randomized and received at least one dose of IP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER