Moderate to Severe Nail Psoriasis
Conditions
Keywords
Moderate nail psoriasis, Severe nail psoriasis, psoriasis, Secukinumab
Brief summary
This purpose of this study was to demonstrate the efficacy of secukinumab versus placebo on nail psoriasis and to assess long-term efficacy, safety and tolerability of secukinumab.
Interventions
BIOLOGICALSecukinumab
Study treatment was provided in pre-filled 1 mL syringes.
BIOLOGICALPlacebo
Placebo was provided in pre-filled 1 mL syringes.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization, including significant nail involvement, defined as Nail Psoriasis Severity Index (NAPSI) score ≥16 AND number of fingernails involved ≥4 AND Psoriasis Area and Severity Index (PASI) score ≥12 AND Body Surface Area (BSA) score ≥10% * Candidates for systemic therapy, i.e. psoriasis inadequately controlled by topical treatment (including super potent topical corticosteroids) and/or phototherapy and/or previous systemic therapy
Exclusion criteria
* Forms of psoriasis other than chronic plaque type psoriasis (e.g., pustular psoriasis, palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic and guttate psoriasis) * Drug-induced psoriasis (e.g. new onset or current exacerbation from β-blockers, calcium channel inhibitors or lithium) * Ongoing inflammatory skin diseases other than psoriasis or any other disease affecting the fingernails which may potentially confound the evaluation of study treatment effects * Ongoing use of prohibited treatments (e.g. topical or systemic corticosteroids (CS), UV therapy). Washout periods do apply * Prior exposure to secukinumab (AIN457) or any other biological drug directly targeting IL-17 or the IL-17 receptor * Exposure to any investigational drugs within 4 weeks prior to study treatment initiation or within a period of 5 half-lives of the investigational treatment, whichever is longer * History of hypersensitivity to constituents of the study treatment * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment | Baseline, 16 weeks | The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement. The adjusted mean is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in NAPSI Score | baseline, 16 weeks, 132 weeks | The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement. |
| Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | 16 weeks, 132 weeks | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). The IGA scale referred exclusively to the participant's disease at the time of the assessment. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. To be considered IGA responder at any point in time, the patient must have an IGA score of 0 or 1 and have achieved a reduction of at least two points on the IGA scale from baseline. |
| Number of Participants Who Develop Immunogenicity Against Secukinumab | Week 132 | The number of participants who tested positive for anti-secukinumab antibodies. It refers to the number of participants who had no positive values at baseline but developed them only after start of secukinumab treatment. None of the participants had a loss of efficacy and the test was only transiently positive. |
Countries
Australia, Belgium, Czechia, Denmark, Germany, Greece, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was made up of 4 periods: screening, treatment period 1, treatment period 2 and post-treatment follow-up.
Pre-assignment details
In treatment period 1, participants were randomized in a 1:1:1 ratio to secukinumab 150mg, secukinumab 300mg or placebo. In treatment period 2, placebo participants were re-randomized in a 1:1 ratio to secukinumab 150mg or secukinumab 300mg. The follow-up period occurred 8 weeks post treatment period 2 (12 weeks post the last dose of secukinumab).
Participants by arm
| Arm | Count |
|---|---|
| AIN457 150 mg Participants assigned to secukinumab 150 mg were dosed weekly for five weeks, then once every four weeks up to and including Week 132. To maintain the blinding, participants received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment were administered by sub-cutaneous injections. | 67 |
| AIN457 300 mg Participants assigned to secukinumab 300 mg were dosed weekly for five weeks, then once every four weeks up to and including Week 132. To maintain the blinding, participants received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment were administered by sub-cutaneous injections. | 66 |
| Placebo Participants who received placebo during treatment period 1 | 65 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Follow-up Period (132-140 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Follow-up Period (132-140 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Follow-up Period (132-140 Weeks) | Study terminated | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 1 (0-16 Weeks) | Adverse Event | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (0-16 Weeks) | Lack of Efficacy | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (0-16 Weeks) | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (0-16 Weeks) | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (0-16 Weeks) | Protocol deviation | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (0-16 Weeks) | Withdrawal by Subject | 0 | 1 | 3 | 0 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Adverse Event | 3 | 3 | 0 | 3 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Lack of Efficacy | 5 | 3 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Lost to Follow-up | 4 | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Non-compliant with study treatment | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Protocol deviation | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Study terminated | 7 | 4 | 0 | 0 | 2 | 0 | 0 |
| Treatment Period 2 (16-132 Weeks) | Withdrawal by Subject | 5 | 6 | 0 | 2 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | AIN457 150 mg | AIN457 300 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 43.5 Years STANDARD_DEVIATION 10.94 | 45.1 Years STANDARD_DEVIATION 12.9 | 43.6 Years STANDARD_DEVIATION 11.2 | 44.1 Years STANDARD_DEVIATION 11.68 |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 13 Participants | 38 Participants |
| Sex: Female, Male Male | 55 Participants | 53 Participants | 52 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 76 / 96 | 79 / 94 | 37 / 65 | 155 / 190 |
| serious Total, serious adverse events | 10 / 96 | 9 / 94 | 1 / 65 | 19 / 190 |
Outcome results
Primary
Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment
The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement. The adjusted mean is presented.
Time frame: Baseline, 16 weeks
Population: Only participants from the full analysis set (FAS) who had values at both baseline and week 16, were analyzed. The FAS consisted of all randomized participants to whom treatment was assigned. The analysis was based on Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 150 mg | Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment | -38.4 percent change | Standard Error 4.54 |
| AIN457 300 mg | Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment | -46.1 percent change | Standard Error 3.43 |
| Placebo | Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment | -11.7 percent change | Standard Error 4.28 |
p-value: <0.000195% CI: [-39.1, -14.3]Mixed model reapeated measures
p-value: <0.000195% CI: [-45.2, -23.5]Mixed model repeated measures
Secondary
Number of Participants Who Develop Immunogenicity Against Secukinumab
The number of participants who tested positive for anti-secukinumab antibodies. It refers to the number of participants who had no positive values at baseline but developed them only after start of secukinumab treatment. None of the participants had a loss of efficacy and the test was only transiently positive.
Time frame: Week 132
Population: Participants from the safety set was analyzed. The safety set included all participants who took at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 150 mg | Number of Participants Who Develop Immunogenicity Against Secukinumab | 2 Participants |
| AIN457 300 mg | Number of Participants Who Develop Immunogenicity Against Secukinumab | 5 Participants |
| Placebo | Number of Participants Who Develop Immunogenicity Against Secukinumab | 4 Participants |
| Placebo - AIN457 300 mg | Number of Participants Who Develop Immunogenicity Against Secukinumab | 3 Participants |
Secondary
Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132
PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). The IGA scale referred exclusively to the participant's disease at the time of the assessment. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. To be considered IGA responder at any point in time, the patient must have an IGA score of 0 or 1 and have achieved a reduction of at least two points on the IGA scale from baseline.
Time frame: 16 weeks, 132 weeks
Population: Participants from the FAS, who had evaluable data at a given time point, were analyzed for that time point. The FAS consisted of all randomized participants to whom treatment was assigned. Multiple imputation was applied where the number of evaluable participants was based on a rounded mean number of responders for 500 imputations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIN457 150 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 16, PASI 75 | 76.6 Percentage of participants |
| AIN457 150 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 16, IGA 0/1 | 67.8 Percentage of participants |
| AIN457 150 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 132, PASI 75 | 61.6 Percentage of participants |
| AIN457 150 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 132, IGA 0/1 | 52.2 Percentage of participants |
| AIN457 300 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 132, IGA 0/1 | 61.2 Percentage of participants |
| AIN457 300 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 16, PASI 75 | 87.1 Percentage of participants |
| AIN457 300 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 132, PASI 75 | 82.7 Percentage of participants |
| AIN457 300 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | Week 16, IGA 0/1 | 74.0 Percentage of participants |
Secondary
Percent Change From Baseline in NAPSI Score
The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement.
Time frame: baseline, 16 weeks, 132 weeks
Population: Only participants from the full analysis set (FAS) who had values at both baseline and the post-baseline time point, were analyzed. The FAS consisted of all randomized participants to whom treatment was assigned. The analysis was based on Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AIN457 150 mg | Percent Change From Baseline in NAPSI Score | Week 16 | -37.9 percent change | Standard Deviation 37.32 |
| AIN457 150 mg | Percent Change From Baseline in NAPSI Score | Week 132 | -52.9 percent change | Standard Deviation 42.9 |
| AIN457 300 mg | Percent Change From Baseline in NAPSI Score | Week 132 | -70.5 percent change | Standard Deviation 29.2 |
| AIN457 300 mg | Percent Change From Baseline in NAPSI Score | Week 16 | -45.3 percent change | Standard Deviation 27.22 |
| Placebo | Percent Change From Baseline in NAPSI Score | Week 16 | -15.4 percent change | Standard Deviation 32.79 |
| Placebo | Percent Change From Baseline in NAPSI Score | Week 132 | -62.9 percent change | Standard Deviation 29.05 |
| Placebo - AIN457 300 mg | Percent Change From Baseline in NAPSI Score | Week 16 | -7.8 percent change | Standard Deviation 31.77 |
| Placebo - AIN457 300 mg | Percent Change From Baseline in NAPSI Score | Week 132 | -72.7 percent change | Standard Deviation 22.84 |