Back to resultsA Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis
Primary Purpose
Plaque Psoriasis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
AIN457
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Plaque Psoriasis focused on measuring Plaque psoriasis
Eligibility Criteria
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:
- Coverage of the body surface area (BSA) of 10% or more with plaques
- 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.
- 2 months washout prior to screening for etanercept, adalimumab, or infliximab.
- 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/exclusion criteria may apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AIN457
Placebo
Arm Description
AIN457A 3mg/kg was administered intravenously as a single dose.
Placebo was administered intravenously as a single dose.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00669916
Brief Title
A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis
Official Title
Phase 2a Single-Dose, Randomized, Double Blind, Multi-Center, Parallel-Group, Placebo-Controlled Proof of Concept Study to Assess the Efficacy, Safety, Tolerability, and Population Pharmacokinetics of AIN457 in Patients With Stable Plaque-type Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
November 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plaque Psoriasis
Keywords
Plaque psoriasis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AIN457
Arm Type
Experimental
Arm Description
AIN457A 3mg/kg was administered intravenously as a single dose.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered intravenously as a single dose.
Intervention Type
Biological
Intervention Name(s)
AIN457
Intervention Description
single infusion of 3 mg/kg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
single infusion of placebo
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score
Description
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
Title
Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score
Description
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
Secondary Outcome Measure Information:
Title
Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Description
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
Title
Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)
Description
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
Title
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)
Description
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
Title
Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)
Description
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
Title
Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL)
Description
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
Title
Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Coverage of the body surface area (BSA) of 10% or more with plaques
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.
2 months washout prior to screening for etanercept, adalimumab, or infliximab.
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/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
20926833
Citation
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group; Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group; Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group; Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010 Oct 6;2(52):52ra72. doi: 10.1126/scitranslmed.3001107.
Results Reference
derived
Learn more about this trial
A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis
We'll reach out to this number within 24 hrs