Psoriasis
Conditions
Keywords
Genital Psoriasis, CC-10004, Apremilast, Plaque Psoriasis
Brief summary
This Phase 3 multicenter, randomized, placebo-controlled, double-blind study is designed to evaluate the efficacy and safety of apremilast in subjects with moderate to severe genital psoriasis (modified sPGA-G ≥3, moderate or severe). Approximately 286 subjects with moderate to severe genital psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.
Detailed description
The study will consist of four phases: * Screening Phase - up to 35 days * Double-blind Placebo-controlled Phase - Weeks 0 to 16 \- Subjects will be randomly assigned to either apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID. * Apremilast Extension Phase - Weeks 16 to 32 \- All subjects will be switched to (or continue with) apremilast 30 mg BID. All subjects will maintain this dosing through Week 32. * Observational Follow-up Phase - 4 weeks - Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue the study early.
Interventions
DRUGApremilast
Oral
OTHERPlacebo
Oral
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF). 2. Subject must have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF. 3. Subject must have a diagnosis of moderate or severe psoriasis of the genital area at Screening and Baseline. 4. Subject must have a diagnosis of moderate or severe psoriasis at Screening and Baseline. 5. Subject must have plaque psoriasis (BSA ≥ 1%) in a non-genital area at both Screening and Baseline. 6. Subject must have been inadequately controlled with or intolerant of topical therapy, or topical therapy is inappropriate for the treatment of psoriasis affecting the genital area. 7. Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis. 8. Subject must meet laboratory criteria
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: 1. Subject has any significant medical condition or laboratory abnormality, that would prevent the subject from participating in the study. 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Subject has positive Hepatitis B surface antigen or anti-hepatitis C antibody at Screening. 4. Subject has active tuberculosis (TB) or a history of incompletely treated TB. 5. Subject has prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. 6. Subject has current or planned therapies that may have a possible effect on psoriasis of the body and/or genital area during the course of the treatment phase of the trial 7. Subject had prior treatment with apremilast.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Modified sPGA-G Response at Week 16 | Baseline and Week 16 of the Placebo-controlled Phase | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 | Baseline and Week 16 of the placebo-controlled phase | 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. |
| Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16 | Baseline and Week 16 of the placebo-controlled phase | 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. |
| Change From Baseline in Affected Body Surface Area (BSA) at Week 16 | Baseline and Week 16 of the placebo-controlled phase | 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. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline and Week 16 of the placebo-controlled phase | 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. |
| Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score at Week 16 | Baseline and Week 16 of the placebo-controlled phase | 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. |
Countries
Belgium, Canada, France, Germany, Italy, Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at 49 centers in Belgium, Canada, France, Germany, Italy, and the United States from February 2019 to February 2022.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo-controlled Phase: Placebo Participants received placebo as oral tablets BID for up to 16 weeks (Week 0 to Week 16). | 146 |
| 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). | 143 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Apremilast Extension Phase | Adverse Event | 0 | 0 | 6 |
| Apremilast Extension Phase | Lack of Efficacy | 0 | 0 | 1 |
| Apremilast Extension Phase | Lost to Follow-up | 0 | 0 | 7 |
| Apremilast Extension Phase | Miscellaneous | 0 | 0 | 1 |
| Apremilast Extension Phase | Withdrawal by Subject | 0 | 0 | 13 |
| Placebo-controlled Phase | Adverse Event | 8 | 10 | 0 |
| Placebo-controlled Phase | Due to COVID-19 control measures | 1 | 0 | 0 |
| Placebo-controlled Phase | Lack of Efficacy | 0 | 1 | 0 |
| Placebo-controlled Phase | Lost to Follow-up | 7 | 7 | 0 |
| Placebo-controlled Phase | Non-compliance with study drug | 0 | 2 | 0 |
| Placebo-controlled Phase | Physician Decision | 0 | 1 | 0 |
| Placebo-controlled Phase | Withdrawal by Subject | 19 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo-controlled Phase: Placebo | Total | Placebo-controlled Phase: Apremilast 30 mg |
|---|---|---|---|
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 14.38 | 45.0 Years STANDARD_DEVIATION 13.93 | 43.5 Years STANDARD_DEVIATION 13.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 31 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 131 Participants | 256 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Modified Static Physician Global Assessment of Genitalia (sPGA-G) Score 3 (Moderate) | 128 Participants | 251 Participants | 123 Participants |
| Modified Static Physician Global Assessment of Genitalia (sPGA-G) Score 4 (Severe) | 18 Participants | 38 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 131 Participants | 262 Participants | 131 Participants |
| Sex: Female, Male Female | 44 Participants | 87 Participants | 43 Participants |
| Sex: Female, Male Male | 102 Participants | 202 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 145 | 0 / 143 | 0 / 229 |
| other Total, other adverse events | 39 / 145 | 73 / 143 | 53 / 229 |
| serious Total, serious adverse events | 2 / 145 | 3 / 143 | 2 / 229 |
Outcome results
Primary
Percentage of Participants With a Modified sPGA-G Response at Week 16
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.
Time frame: Baseline and Week 16 of the Placebo-controlled Phase
Population: The ITT analysis set consisted of all participants who are randomized regardless of whether the participant received IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With a Modified sPGA-G Response at Week 16 | 19.5 Percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With a Modified sPGA-G Response at Week 16 | 39.6 Percentage of participants |
p-value: 0.000395% CI: [9.2, 30.9]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Affected Body Surface Area (BSA) 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.
Time frame: Baseline and Week 16 of the placebo-controlled phase
Population: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo-controlled Phase: Placebo | Change From Baseline in Affected Body Surface Area (BSA) at Week 16 | -0.79 Change in percentage of affected BSA | Standard Error 0.669 |
| Placebo-controlled Phase: Apremilast 30 mg | Change From Baseline in Affected Body Surface Area (BSA) at Week 16 | -4.12 Change in percentage of affected BSA | Standard Error 0.664 |
p-value: 0.000595% CI: [-5.18, -1.47]MMRM
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) 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.
Time frame: Baseline and Week 16 of the placebo-controlled phase
Population: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo-controlled Phase: Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -2.6 Scores on a scale | Standard Error 0.57 |
| Placebo-controlled Phase: Apremilast 30 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | -5.3 Scores on a scale | Standard Error 0.55 |
p-value: 0.000895% CI: [-4.2, -1.1]MMRM
Secondary
Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score 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.
Time frame: Baseline and Week 16 of the placebo-controlled phase
Population: ITT analysis set with Baseline and at least one post-baseline value at Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo-controlled Phase: Placebo | Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score at Week 16 | -5.3 Score on a scale | Standard Error 1.85 |
| Placebo-controlled Phase: Apremilast 30 mg | Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score at Week 16 | -20.5 Score on a scale | Standard Error 1.83 |
p-value: <0.000195% CI: [-20.3, -10]MMRM
Secondary
Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16
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.
Time frame: Baseline and Week 16 of the placebo-controlled phase
Population: ITT analysis set with Baseline GPI-NRS score ≥ 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16 | 19.6 Percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16 | 47.3 Percentage of participants |
p-value: <0.000195% CI: [15.4, 39.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16
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.
Time frame: Baseline and Week 16 of the placebo-controlled phase
Population: The ITT analysis set consisted of all participants who are randomized regardless of whether the participant received IP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo-controlled Phase: Placebo | Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 | 6.9 Percentage of participants |
| Placebo-controlled Phase: Apremilast 30 mg | Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 | 22.2 Percentage of participants |
p-value: 0.000495% CI: [6.9, 23.6]Cochran-Mantel-Haenszel