Psoriasis
Conditions
Keywords
Psoriasis, Chronic Plaque Psoriasis, Secukinumab
Brief summary
Mild psoriasis not only progresses to moderate-to-severe psoriasis but also precedes systemic inflammation that leads to psoriatic arthritis and cardiovascular comorbidities. By curing mild psoriasis with a short-term anti- interleukin (IL)-17A treatment, investigators may reduce the costs of treating psoriasis and associated medical conditions, including psoriatic arthritis, cardiovascular disease, and diabetes.
Detailed description
Psoriasis is an immune-mediated disease of the skin that, even in mild disease, increases the risk of comorbidities such as cardiovascular disease and metabolic derangements. Mild psoriasis tends to be treated with topical drugs, while moderate-to-severe disease is optimally treated with systemic immune modulators. However, the treatment of mild psoriasis needs to be re-thought because recent studies have revealed that mild psoriasis is characterized by stronger expression of pathogenic molecules, such as interleukin (IL)-17A, and higher numbers of T cells in the skin, compared to severe psoriasis. A key distinction between mild and severe psoriasis is now discovered to be the higher expression of negative immune regulatory genes in mild lesions. Therefore, targeted immune therapy with anti-IL-17A, which is highly effective in severe psoriasis, might be equally (or even more) effective in mild disease. Also, restoration of immune tolerance might be more easily achieved in mild disease. Thus, short-term anti-IL-17A treatment of mild psoriasis might prevent the recurrence and eventually cure the disease. The aim of study is to test this hypothesis by exploring whether 3 months or 6 months of anti-IL17A treatment will prevent relapses after medication has been discontinued in mild psoriasis patients.
Interventions
DRUGSecukinumab
Arms: Group 1 - Group 1 will receive Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period. In order to maintain the blind for the Group 2, Group 1 will receive placebo injections at weeks 13, 14, and 15. Group 1 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).
DRUGPlacebo followed by Secukinumab
Arms: Group 2 - Group 2 will receive placebo injections corresponding to the Group 1 regimen until week 8 in order to maintain a double-dummy design until week 12. From week 12, Group 2 will receive Secukinumab with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period. Group 2 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).
Sponsors
Novartis
James G. Krueger, MD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
To compare the secukinumab-receiving mild psoriasis subjects (Group 1) and the placebo-receiving mild psoriasis subjects (Group 2).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before any assessment is performed 2. 18 years of age or older 3. Chronic plaque-type psoriasis for at least 6 months 4. Negative PPD (negative chest w-ray if positive) or negative QuantiFERON-TB Gold 5. Have a PASI between 6 and 12 and Body Surface Area (BSA) affected by plaque-type psoriasis less than 10% at screening and baseline 6. Willing to wash off steroid creams and ultraviolet B light (UVB) therapy for 2 weeks prior to the baseline visit
Exclusion criteria
1. Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular) 2. Has previously received Secukinumab or other biologics 3. History of Inflammatory Bowel Disease (IBD) 4. History of Rheumatoid Arthritis 5. Use of topical treatments for psoriasis, including steroids, vitamin D derivatives, vitamin A derivatives, salicylic acid, tar (except moisturizers) and/or ultraviolet A light (UVA)/UVB phototherapy within the last 2 weeks (if these have used them, the participant needs to wash off of them for at least 2 weeks after signing consent prior to baseline) 6. Is pregnant, nursing, or planning a pregnancy (both men and women) within 5 months following the last administration of study drug 7. Has recently received or is planning to receive a vaccination while on the study 8. HIV positive 9. Chronic untreated hepatitis C, positive hepatitis B surface antigen and acute hepatitis A infection 10. Known tuberculosis (TB) or evidence of TB infection. Subjects with a positive QuantiFERON; TB test or a positive purified protein derivate (PPD) skin test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active TB. 11. Any severe, progressive or uncontrolled medical condition at screening that in the judgment of the investigator prevents the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75) | week 12 | The percentage of subjects who have a reduction of 75% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 75). Psoriasis Area and Severity Index (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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate). | week 12 | Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) score of 0 or 1 with at least a 2-step improvement from baseline (PGA 0/1 response rate). Physician Global Assessment (PGA) is a global assessment of all psoriasis lesions scored on a scale of 0-5, with 0 representing clear skin, 1 almost clear skin, and 5 representing severe psoriasis |
| Percentage of Subjects Who Experience Psoriasis Relapse | week 24 through week 72 | The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72. Psoriasis relapse is defined as loss of \> 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (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) |
| Percentage of Subjects Who Experience Severe Psoriasis Relapse | Observation Period: week 24 through week 72. | The percentage of subjects who experience a severe psoriasis relapse at any time between week 24 and week 72. Severe psoriasis relapse is defined as loss of \> 75% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (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) |
| Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared | Observation Period: week 24 through week 72 | The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72 among the subjects whose psoriasis is cleared between week 0 and week 24. Psoriasis relapse is defined as loss of \> 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis clearance is defined as the achievement of PASI100, which is a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score. Psoriasis Area and Severity Index (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). |
| Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90) | week 12 | The percentage of subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 90). Psoriasis Area and Severity Index (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) |
| Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100) | week 12 | The percentage of subjects who have a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI100) at week 12. Psoriasis Area and Severity Index (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) |
| Frequency of Adverse Events | week 0 through week 72 | Frequency of all Adverse Events (AEs) including Serious Adverse Events (SAEs) that occur during the whole trial including the observational period (AEs and SAEs include but not limited to comorbidities, such as hypertension, diabetes, and cardiovascular diseases). |
| Frequency of Serious Adverse Events | week 0 through week 72 | Frequency of Serious Adverse Events (SAEs) that occur during the whole trial including the observational period. |
| Elapsed Time Until Relapse | week 24 until week 72 | Elapsed time from week 24 until relapse occurs before week 72, measured in weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 6 months of Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period.
Secukinumab: Arms: Group 1 - Group 1 will receive Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period. In order to maintain the blind for the Group 2, Group 1 will receive placebo injections at weeks 13, 14, and 15. Group 1 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks). | 12 |
| Group 2 Placebo followed by Secukinumab. 3 months of placebo followed by 3 months of Secukinumab at a dose of 300 mg with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period.
Placebo followed by Secukinumab: Arms: Group 2 - Group 2 will receive placebo injections corresponding to the Group 1 regimen until week 8 in order to maintain a double-dummy design until week 12. From week 12, Group 2 will receive Secukinumab with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period. Group 2 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks). | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 | Total | Group 1 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 21 Participants | 10 Participants |
| Age, Continuous | 43 years | 44.0 years | 47 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 15 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Psoriasis Area-Severity Index (PASI) | 8.900 units on a scale | 8.200 units on a scale | 7.100 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 13 Participants | 7 Participants |
| Region of Enrollment United States | 11 participants | 23 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 16 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 10 / 12 | 9 / 11 |
| serious Total, serious adverse events | 1 / 12 | 0 / 11 |
Outcome results
Primary
Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75)
The percentage of subjects who have a reduction of 75% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 75). Psoriasis Area and Severity Index (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)
Time frame: week 12
Population: One participant in Group 1 was not included in the data analysis due to a serious adverse event before the primary endpoint, unrelated to study medication or study participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75) | 8 Participants |
| Group 2 | Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75) | 0 Participants |
Secondary
Elapsed Time Until Relapse
Elapsed time from week 24 until relapse occurs before week 72, measured in weeks.
Time frame: week 24 until week 72
Population: The overall number of participants analyzed is lower than the total enrollment for the study, because of loss to follow up during the observation period between week 24 and week 72. The loss to follow-up disabled the statistical analyses of the outcome measure data. There were various reasons for loss to follow-up including the negative impacts of COVID-19 to the participants during the observation period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 | Elapsed Time Until Relapse | 24 weeks |
| Group 2 | Elapsed Time Until Relapse | 48 weeks |
Secondary
Frequency of Adverse Events
Frequency of all Adverse Events (AEs) including Serious Adverse Events (SAEs) that occur during the whole trial including the observational period (AEs and SAEs include but not limited to comorbidities, such as hypertension, diabetes, and cardiovascular diseases).
Time frame: week 0 through week 72
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Frequency of Adverse Events | 22 events |
| Group 2 | Frequency of Adverse Events | 13 events |
Secondary
Frequency of Serious Adverse Events
Frequency of Serious Adverse Events (SAEs) that occur during the whole trial including the observational period.
Time frame: week 0 through week 72
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Frequency of Serious Adverse Events | 1 events |
| Group 2 | Frequency of Serious Adverse Events | 0 events |
Secondary
Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate).
Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) score of 0 or 1 with at least a 2-step improvement from baseline (PGA 0/1 response rate). Physician Global Assessment (PGA) is a global assessment of all psoriasis lesions scored on a scale of 0-5, with 0 representing clear skin, 1 almost clear skin, and 5 representing severe psoriasis
Time frame: week 12
Population: One participant in Group 1 was not included in the data analysis due to a serious adverse event before the primary endpoint, unrelated to study medication or study participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate). | 9 Participants |
| Group 2 | Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate). | 0 Participants |
Secondary
Percentage of Subjects Who Experience Psoriasis Relapse
The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72. Psoriasis relapse is defined as loss of \> 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (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)
Time frame: week 24 through week 72
Population: The overall number of participants analyzed is lower than the total enrollment for the study, because of loss to follow up during the observation period between week 24 and week 72. The loss to follow-up disabled the statistical analyses of the outcome measure data. There were various reasons for loss to follow-up including the negative impacts of COVID-19 to the participants during the observation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Experience Psoriasis Relapse | 3 Participants |
| Group 2 | Percentage of Subjects Who Experience Psoriasis Relapse | 2 Participants |
Secondary
Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared
The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72 among the subjects whose psoriasis is cleared between week 0 and week 24. Psoriasis relapse is defined as loss of \> 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis clearance is defined as the achievement of PASI100, which is a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score. Psoriasis Area and Severity Index (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).
Time frame: Observation Period: week 24 through week 72
Population: The overall number of participants analyzed is lower than the total enrollment for the study, because of loss to follow up during the observation period between week 24 and week 72. The loss to follow-up disabled the statistical analyses of the outcome measure data. There were various reasons for loss to follow-up including the negative impacts of COVID-19 to the participants during the observation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared | 1 Participants |
| Group 2 | Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared | 1 Participants |
Secondary
Percentage of Subjects Who Experience Severe Psoriasis Relapse
The percentage of subjects who experience a severe psoriasis relapse at any time between week 24 and week 72. Severe psoriasis relapse is defined as loss of \> 75% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (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)
Time frame: Observation Period: week 24 through week 72.
Population: The overall number of participants analyzed is lower than the total enrollment for the study, because of loss to follow up during the observation period between week 24 and week 72. The loss to follow-up disabled the statistical analyses of the outcome measure data. There were various reasons for loss to follow-up including the negative impacts of COVID-19 to the participants during the observation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Experience Severe Psoriasis Relapse | 2 Participants |
| Group 2 | Percentage of Subjects Who Experience Severe Psoriasis Relapse | 1 Participants |
Secondary
Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100)
The percentage of subjects who have a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI100) at week 12. Psoriasis Area and Severity Index (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)
Time frame: week 12
Population: One participant in Group 1 was not included in the data analysis due to a serious adverse event before the primary endpoint, unrelated to study medication or study participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100) | 4 Participants |
| Group 2 | Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100) | 0 Participants |
Secondary
Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90)
The percentage of subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 90). Psoriasis Area and Severity Index (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)
Time frame: week 12
Population: One participant in Group 1 was not included in the data analysis due to a serious adverse event before the primary endpoint, unrelated to study medication or study participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90) | 7 Participants |
| Group 2 | Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90) | 0 Participants |