Plaque Psoriasis
Conditions
Keywords
Plaque psoriasis
Brief summary
This is a two-arm, parallel group, double-blind, placebo-controlled proof-of-concept study comparing 3 mg/kg of AIN457 to placebo. Subjects with a diagnosis of moderate to severe stable plaque psoriasis will be randomized to receive either AIN457 or placebo. AIN457 or placebo will be administered by single infusion at baseline and subjects will be observed for up to 26 weeks following the infusion.
Interventions
BIOLOGICALAIN457
single infusion of 3 mg/kg
DRUGPlacebo
single infusion of placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males or females, aged 18-69 at time of consent. * Post menopausal or surgically sterile female patients are allowed. Male patients must be willing to use contraception method at least for 3 months following the completion of the study. Women of child-bearing potential will not be allowed to participate. * Diagnosis of plaque psoriasis for at least 6 months prior to screening. The patients must meet both of the following criterion: 1. Coverage of the body surface area (BSA) of 10% or more with plaques 2. A score of 3 or more on the IGA scale * Stable plaque psoriasis at screening and randomization. * PASI score of 12 or greater at randomization. * Able to communicate well with the investigator, and to understand and comply with the requirements of the study. Understand and sign the written informed consent. * Patients must have normal laboratory values for screening laboratory test results of hematological (hemoglobin, WBCs, neutrophils, platelets) and renal (serum creatinine) assessments. For the transaminases, aspartate aminotransferase and alanine aminotransferase, levels 1.5 times the upper limit of normal will be accepted. For the additional hepatic laboratory results (alkaline phosphatase, gamma-glutamyltransferase, bilirubin), patients must have non-clinically significant values.
Exclusion criteria
* Currently have any of the nonplaque forms of psoriasis: erythrodermic, guttate, or pustular. * Currently have drug-induced psoriasis (new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium). * Men who are planning to initiate a pregnancy while enrolled in the study or for 3 months following completion of the study. * Women of child-bearing potential are not allowed in the study. * Used any investigational drug within the previous 4 weeks. * Recent previous treatment with anti-TNF-α therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial. 1. 2 months washout prior to screening for etanercept, adalimumab, or infliximab. 2. 1 month washout prior to screening for cyclosporine, mycophenolate, tacrolimus, and any systemic immunosuppressants including, but not limited to, methotrexate, azathioprine, 6-thioguanine, mercaptopurine, and hydroxyurea Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score | Baseline, Week 4 | The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement. |
| Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Baseline, Week 4 | The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
| Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
| Pharmacokinetics of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
| Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
| Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
| Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2) | Day 182 | Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AIN457 AIN457A 3mg/kg was administered intravenously as a single dose. | 18 |
| Placebo Placebo was administered intravenously as a single dose. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | AIN457 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.7 Years STANDARD_DEVIATION 8.73 | 50.9 Years STANDARD_DEVIATION 12.04 | 50.8 Years STANDARD_DEVIATION 10.37 |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 18 | 8 / 18 |
| serious Total, serious adverse events | 1 / 18 | 0 / 18 |
Outcome results
Primary
Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score
The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement.
Time frame: Baseline, Week 4
Population: All participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AIN457 | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = -1 | 5.6 Percentage of participants |
| AIN457 | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 1 | 33.3 Percentage of participants |
| AIN457 | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 0 | 11.1 Percentage of participants |
| AIN457 | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 2 | 44.4 Percentage of participants |
| AIN457 | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 3 | 5.6 Percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 3 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = -1 | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 0 | 77.8 Percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 1 | 11.1 Percentage of participants |
| Placebo | Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score | Change in IGA score = 2 | 0 Percentage of participants |
Primary
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score
The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement.
Time frame: Baseline, Week 4
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AIN457 | Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score | 58 Percentage change in PASI mean score |
| Placebo | Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score | 4 Percentage change in PASI mean score |
Secondary
Pharmacokinetics of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: All AIN457A treatment group participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) | AUClast | 1532 day*ug/mL | Standard Deviation 343 |
| AIN457 | Pharmacokinetics of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) | AUCinf | 1629 day*ug/mL | Standard Deviation 361 |
Secondary
Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) | 74.5 ug/mL | Standard Deviation 13.1 |
Secondary
Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) | 0.18 Liters/day | Standard Deviation 0.05 |
Secondary
Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: All AIN457A treatment group participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2) | 29.2 day | Standard Deviation 6.4 |
Secondary
Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: The population included all AIN457 treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.11 days |
Secondary
Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)
Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time frame: Day 182
Population: The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIN457 | Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) | 7.31 Liters | Standard Error 1.72 |