Chronic Plaque Psoriasis
Conditions
Keywords
Cyclosporine, chronic plaque psoriasis, intermittent therapy
Brief summary
The study will evaluate the efficacy of cyclosporine at 2, 5 mg/kg/day bid (i.e. bis in a day), when administered twice a week compared to continuous administration, in patients with chronic plaque psoriasis.
Interventions
Oral soft gelatin capsules of Cyclosporine 10 mg, 25 mg, 50 mg or 100 mg administered twice a week for 24 weeks at the dosage of 5 mg/Kg/day in two daily administrations
DRUGPlacebo
Oral soft gelatin capsules of placebo matching cyclosporine administered twice a week for 24 weeks in two daily administrations
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Inclusion criteria
* Outpatients 18 years of age and older (max 65 years) * Patients with chronic plaque psoriasis on disease remission (i.e. PASI ≤75% of PASI before cyclosporine continuous treatment course) entering a maintenance period * Disease remission obtained with only cyclosporine as systemic therapy (maximum dose 5 mg/kg/day) for \>8 weeks and \<16 weeks * PASI still \<75% of PASI before cyclosporine continuous treatment course, at randomization to study treatment (8±2 days after disease remission)
Exclusion criteria
* Abnormal renal function (creatinine ≥ 10% the upper limit of the reference range) * Severe chronic degenerative diseases * Severe uncontrolled hypertension * Body weigh \>110 kg * Abnormal liver function * Hyperkalemia or hyperuricemia * Clinically significant impairment of hematopoietic and cardiovascular function * Concomitant therapy with nephrotoxic medications * Patients with malignancy or a history of malignancy * Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception * Clinically significant uncontrolled bacterial, viral or fungal infection * Evidence of drug and/or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score | 24 weeks | PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (best) to 72 (worst), with the highest score representing complete erythroderma of severest degree. Relapse is considered a worsening of psoriasis associated to a PASI score \>75% of PASI score recorded before starting induction therapy with CsA (before study start). Each patient was considered as failure (relapse occurrence) if rate was \>= 75%. In all the other cases the patient was considered as success (no relapse). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Clinical Relapse | 24 weeks | Clinical relapse was defined as worsening of psoriasis associated with a Psoriasis Area and Severity Index (PASI) \>75% of the PASI score assessed before the continuous treatment, or when the investigator or the patient judged it necessary to change the treatment. |
| Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | baseline and week 24 | PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (best) to 72 (worst), with the highest score representing complete erythroderma of the severest degree. |
| Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis | Baseline and week 24 | BSA is a measure of the percentage of body surface affected by psoriasis. Using the Mosteller Formula: BSA = BSA (m²) = ( \[Height(in) x Weight(lbs) \]/ 3131 )½ . A covariance analysis was performed on all variables, with value assessed at visit 2 as covariate and center as effect. For each variable the changes versus the last available measures were computed |
| Change From Baseline in Visual Analogue Scale (VAS) for Patient Self Assessment of Pruritus | Baseline and week 24 | Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 24 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis). |
| Safety / Tolerability Assessed by Adverse Events | 24weeks | — |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine A Oral soft gelatin capsules of cyclosporine 10 mg, 25 mg, 50 mg or 100 mg administered twice a week for 24 weeks at the dosage of 5 mg/Kg/day in two daily administrations. | 160 |
| Placebo Oral soft gelatin capsules of placebo matching cyclosporine administered twice a week for 24 weeks in two daily administrations. | 79 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 |
| Overall Study | Lack of Efficacy | 42 | 27 |
| Overall Study | Other | 24 | 15 |
Baseline characteristics
| Characteristic | Total | Placebo | Cyclosporine A |
|---|---|---|---|
| Age, Customized >=65 years | 3 Participants | 2 Participants | 1 Participants |
| Age, Customized between 18-45 years | 148 Participants | 48 Participants | 100 Participants |
| Age, Customized Between 46 and 65 years | 88 Participants | 29 Participants | 59 Participants |
| Sex: Female, Male Female | 87 Participants | 32 Participants | 55 Participants |
| Sex: Female, Male Male | 152 Participants | 47 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 160 | 1 / 79 |
| serious Total, serious adverse events | 1 / 160 | 0 / 79 |
Outcome results
Primary
Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score
PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (best) to 72 (worst), with the highest score representing complete erythroderma of severest degree. Relapse is considered a worsening of psoriasis associated to a PASI score \>75% of PASI score recorded before starting induction therapy with CsA (before study start). Each patient was considered as failure (relapse occurrence) if rate was \>= 75%. In all the other cases the patient was considered as success (no relapse).
Time frame: 24 weeks
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclosporine A | Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score | Success at 6 months | 87 Participants |
| Cyclosporine A | Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score | Failure at 6 months | 73 Participants |
| Placebo | Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score | Success at 6 months | 36 Participants |
| Placebo | Number of Participants With Relapse Rate (Success or Failure), as Assessed by Psoriasis Area and Severity Index (PASI) Score | Failure at 6 months | 43 Participants |
Secondary
Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis
BSA is a measure of the percentage of body surface affected by psoriasis. Using the Mosteller Formula: BSA = BSA (m²) = ( \[Height(in) x Weight(lbs) \]/ 3131 )½ . A covariance analysis was performed on all variables, with value assessed at visit 2 as covariate and center as effect. For each variable the changes versus the last available measures were computed
Time frame: Baseline and week 24
Population: Intent to Treat (ITT) population. Patients with a value of BSA at baseline and 24 weeks were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporine A | Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis | 8.12 BSA (m^2) | Standard Deviation 12.9 |
| Placebo | Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis | 10.45 BSA (m^2) | Standard Deviation 16.7 |
Secondary
Change From Baseline in Psoriasis Area and Severity Index (PASI) Score
PASI is an index used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (best) to 72 (worst), with the highest score representing complete erythroderma of the severest degree.
Time frame: baseline and week 24
Population: Intention to treat (ITT) population. Patients with a value of PASI at baseline and 24 weeks were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporine A | Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | 5.70 Units on a scale | Standard Deviation 8 |
| Placebo | Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | 6.86 Units on a scale | Standard Deviation 8.4 |
Secondary
Change From Baseline in Visual Analogue Scale (VAS) for Patient Self Assessment of Pruritus
Target lesion pruritus as measured by the Visual Analog Scale (VAS) from 0 to 100 mm at week 24 compared to baseline (with 0 being no pruritis and 100 being maximum pruritis).
Time frame: Baseline and week 24
Population: Intent to treat (ITT) population. Patients with a value of VAS at baseline and 24 weeks were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporine A | Change From Baseline in Visual Analogue Scale (VAS) for Patient Self Assessment of Pruritus | 17.32 Units on a scale | Standard Deviation 30.9 |
| Placebo | Change From Baseline in Visual Analogue Scale (VAS) for Patient Self Assessment of Pruritus | 25.44 Units on a scale | Standard Deviation 31.9 |
Secondary
Proportion of Participants With Clinical Relapse
Clinical relapse was defined as worsening of psoriasis associated with a Psoriasis Area and Severity Index (PASI) \>75% of the PASI score assessed before the continuous treatment, or when the investigator or the patient judged it necessary to change the treatment.
Time frame: 24 weeks
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine A | Proportion of Participants With Clinical Relapse | 0.369 proportion of participants |
| Placebo | Proportion of Participants With Clinical Relapse | 0.456 proportion of participants |
Secondary
Safety / Tolerability Assessed by Adverse Events
Time frame: 24weeks