Psoriasis, Plaque-type Psoriasis
Conditions
Keywords
Psoriasis, Plaque-type psoriasis, Plaque, Secukinumab, AIN457A, PASI, DLQI, IGA
Brief summary
This study is designed to evaluate the proportion of patients achieving reversal of chronic plaque psoriasis at week 4 and 12 following multiple doses of secukinumab administered subcutaneously (sc) compared to placebo. Starting from week 13, all patients will receive multiple doses of secukinumab up to week 52 to study long term effects of secukinumab. Clinical endpoints including biomarker assessments, PASI, IGA and DLQI will be compared to better understand, why secukinumab may be effective in psoriasis patients.
Interventions
DRUGsecukinumab
secukinumab
DRUGplacebo
placebo comparator
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Chronic plaque-type psoriasis diagnosed for at least 6 months * Moderate to severe psoriasis as defined by: PASI score of ≥12, IGA score of ≥3, BSA (body surface area) affected by plaque-type psoriasis of ≥10% * Chronic plaque-type psoriasis considered inadequately controlled by: topical treatment and/or; phototherapy and/or previous systemic therapy
Exclusion criteria
* Forms of psoriasis other than chronic plaque-type * Evidence of skin conditions at the time of the screening visit (e.g., eczema) that would interfere with evaluations of the effect of the investigational product on psoriasis * History or evidence of active tuberculosis or evidence of latent tuberculosis (or other infections like Hepatitis-C/B), malignancy; active or known use of other immunosuppressive drugs (for eg: AIDs, RA, organ rejection etc.) at the screening visit * Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Skin Histology Response After Secukinumab Treatment From Baseline to Week 12 | Baseline, Week 12 | Histological sections of lesional and nonlesional skin biopsies at baseline and at Week 12 were examined. For each visit, each patient's lesional skin biopsy was scored for the degree of histological improvement compared to that patient's baseline disease on a five point scale; - 1 (worse) to +3 (excellent). Histological disease reversal or excellent improvement (histological disease reversal score = 3) was declared at the endpoint when all of the following four criteria were met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Skin Histological Disease Reversal at Week 52 | Week 52 | Histological sections of lesional and nonlesional skin biopsies at Week 52 were examined. For each visit, each patient's lesional skin biopsy was scored for the degree of histological improvement compared to that patient's baseline disease on a five point scale; - 1 (worse) to +3 (excellent). Histological disease reversal or excellent improvement (histological disease reversal score = 3) was declared at the endpoint when all of the following four criteria were met. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AIN457 300mg AIN457 300mg subcutaneously weekly | 24 |
| Placebo Placebo subcutaneously weekly until Week 12. At week 12, participants received AIN457 300mg subcutaneously weekly. | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | AIN457 300mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 14 | 50.3 years STANDARD_DEVIATION 13.8 | 48.4 years STANDARD_DEVIATION 13.8 |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 17 Participants | 6 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 24 | 8 / 12 |
| serious Total, serious adverse events | 1 / 24 | 0 / 12 |
Outcome results
Primary
Percentage of Participants Achieving Skin Histology Response After Secukinumab Treatment From Baseline to Week 12
Histological sections of lesional and nonlesional skin biopsies at baseline and at Week 12 were examined. For each visit, each patient's lesional skin biopsy was scored for the degree of histological improvement compared to that patient's baseline disease on a five point scale; - 1 (worse) to +3 (excellent). Histological disease reversal or excellent improvement (histological disease reversal score = 3) was declared at the endpoint when all of the following four criteria were met.
Time frame: Baseline, Week 12
Population: PharmacoDynamic PD -All patients with at least one evaluable post-treatment PD measurement and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 300mg | Percentage of Participants Achieving Skin Histology Response After Secukinumab Treatment From Baseline to Week 12 | 56.5 percentage of participants |
| Placebo | Percentage of Participants Achieving Skin Histology Response After Secukinumab Treatment From Baseline to Week 12 | 0.0 percentage of participants |
p-value: <0.00195% CI: [0.363, 0.768]Fisher Exact
Secondary
Percentage of Participants Achieving Skin Histological Disease Reversal at Week 52
Histological sections of lesional and nonlesional skin biopsies at Week 52 were examined. For each visit, each patient's lesional skin biopsy was scored for the degree of histological improvement compared to that patient's baseline disease on a five point scale; - 1 (worse) to +3 (excellent). Histological disease reversal or excellent improvement (histological disease reversal score = 3) was declared at the endpoint when all of the following four criteria were met.
Time frame: Week 52
Population: PharmacoDynamic PD -All patients with at least one evaluable post-treatment PD measurement and no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 300mg | Percentage of Participants Achieving Skin Histological Disease Reversal at Week 52 | 62.5 percentage of participants |
| Placebo | Percentage of Participants Achieving Skin Histological Disease Reversal at Week 52 | 33.3 percentage of participants |