Plaque-type Psoriasis
Conditions
Keywords
Chronic plaque-type psoriasis, AIN457, dermatology, Moderate to severe chronic plaque-type psoriasis
Brief summary
The purpose of this study was to provide long term clinical data for the compound for the treatment of the indication of moderate to severe chronic plaque-type psoriasis.
Detailed description
In the Proof-of-Concept study (CAIN457A2102/ NCT00669916), AIN457 was proven to be efficacious in the treatment of moderate to severe chronic plaque-type psoriasis. As a result, a phase IIb regimen finding study had been started (CAIN457A2211/NCT00941031). The data gathered in this extension study of the core study (CAIN457A2211)was used to expand the safety database of the compound for the treatment of moderate to severe chronic plaque-type psoriasis. The participants in the extension study continued to stay on the exact same treatment regimen they were taking when completing the core study. The extension trial was first designed to provide long-term safety data of up to 100 weeks of treatment (32 weeks in the core study plus 68 weeks in the extension study (part 1)), and an additional 12 weeks of treatment-free follow-up for participants who did not continue in the extension study. Amendment 2 provided an additional 156 weeks of treatment (32 weeks in the core study plus 224 weeks in the extension study, equaling 256 weeks of total treatment (part 2)), before participants entered the 12 weeks of treatment-free follow-up. Protocol Amendment 3 extended the prolongation part of the study by up to 104 additional weeks of treatment (part 3) or until the drug was commercially available in the market of the country of participation, whichever occurred first.
Interventions
DRUGAIN457
AIN457A 150 mg powder for solution
DRUGPlacebo
Placebo to AIN457A 150 mg powder for solution
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
Key Inclusion Criteria: * Patients who completed the core study CAIN457A2211. A patient is defined as having completed the core study if he/she completed the study up to and including visit 13 (F4) of the core study * Patients must be able to understand and communicate with the investigator and comply with the requirement of the study and must given written, signed and dated informed consent before any study assessment is performed. * Patients must be expected to benefit from the ongoing treatment with AIN457, as assessed by the patient and investigator * Male patients must consent to practice reliable contraception during the study and for 16 weeks after the last dose of study drug administration Note: Due to new data available from the toxicology studies, the need for male contraception was removed. Key
Exclusion criteria
* Patients who experience a second consecutive full relapse at visit 13 ( week F4) of the core study CAIN457A2211 * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive hCG laboratory test (\> 5mlU/mL) * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 16 weeks after stopping treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Serious Adverse Events and Deaths | up to week 351 | Safety was assessed by frequency of adverse events including serious adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension weeks: 1, 25, 73 and 301 (too few data points were available to perform analysis at week 301) | 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 is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. |
| Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial | up to week 351 | Describes the number of participants 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. |
Countries
France, Germany, Iceland, Israel, Japan, Norway, United States
Participant flow
Pre-assignment details
Participants continued their regimens as assigned in CAIN457A2211 (NCT00941031) and were enrolled into one of the following: fixed time interval regimen (FI), treatment at start of relapse regimen (SR) or open-label (OL). There were no more placebo treated patients at the end of the core. Therefore, there is no placebo arm in the extension.
Participants by arm
| Arm | Count |
|---|---|
| Fixed-time Interval Regimen Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter | 46 |
| Treatment at Start of Relapse Regimen Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks | 42 |
| Open-label Secukinumab 150 mg sc administered every 4 weeks. | 187 |
| Total | 275 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative problems | 5 | 1 | 52 |
| Overall Study | Adverse Event | 5 | 2 | 15 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 23 | 22 | 73 |
| Overall Study | Lost to Follow-up | 2 | 2 | 7 |
| Overall Study | Protocol deviation | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 8 | 19 |
Baseline characteristics
| Characteristic | Fixed-time Interval Regimen | Treatment at Start of Relapse Regimen | Open-label | Total |
|---|---|---|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 13.71 | 39.9 Years STANDARD_DEVIATION 12.12 | 45.0 Years STANDARD_DEVIATION 11.78 | 43.9 Years STANDARD_DEVIATION 12.27 |
| Sex: Female, Male Female | 15 Participants | 12 Participants | 39 Participants | 66 Participants |
| Sex: Female, Male Male | 31 Participants | 30 Participants | 148 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 46 | 35 / 42 | 164 / 187 |
| serious Total, serious adverse events | 9 / 46 | 4 / 42 | 43 / 187 |
Outcome results
Primary
Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Safety was assessed by frequency of adverse events including serious adverse events.
Time frame: up to week 351
Population: Extension safety set: the extension safety set consisted of all participants who received at least one dose of study drug during the extension and had at least one post-baseline safety assessment during the extension.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fixed-time Interval Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Serious adverse events | 9 Participants |
| Fixed-time Interval Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Adverse events | 44 Participants |
| Fixed-time Interval Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Deaths | 0 Participants |
| Treatment at Start of Relapse Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Serious adverse events | 4 Participants |
| Treatment at Start of Relapse Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Adverse events | 41 Participants |
| Treatment at Start of Relapse Regimen | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Deaths | 0 Participants |
| Open-label | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Adverse events | 180 Participants |
| Open-label | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Deaths | 1 Participants |
| Open-label | Number of Participants With Adverse Events, Serious Adverse Events and Deaths | Serious adverse events | 43 Participants |
Secondary
Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial
Describes the number of participants 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.
Time frame: up to week 351
Population: Extension safety set: the extension safety set consisted of all participants who received at least one dose of study drug during the extension and had at least one post-baseline safety assessment during the extension.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fixed-time Interval Regimen | Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial | 0 Participants |
| Treatment at Start of Relapse Regimen | Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial | 0 Participants |
| Open-label | Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial | 1 Participants |
Secondary
Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response
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 is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe.
Time frame: Extension weeks: 1, 25, 73 and 301 (too few data points were available to perform analysis at week 301)
Population: Full analysis set (FAS): The FAS, which included all participants who entered the extension and to whom study drug was assigned, was considered for the analysis. Only those participants, who had evaluable data at a given time point, were analyzed at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 1, IGA mod 2009 0 or 1 | 24 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 90 | 8 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 73, IGA mod 2009 | 9 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 50 | 29 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 75 | 19 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 25, IGA mod 2009 0 or 1 | 15 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 90 | 17 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 50 | 43 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 90 | 12 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 75 | 31 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 50 | 18 Number of participants |
| Fixed-time Interval Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 75 | 14 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 50 | 17 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 75 | 8 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 1, IGA mod 2009 0 or 1 | 7 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 90 | 2 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 90 | 1 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 90 | 3 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 73, IGA mod 2009 | 4 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 75 | 16 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 25, IGA mod 2009 0 or 1 | 4 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 50 | 27 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 50 | 34 Number of participants |
| Treatment at Start of Relapse Regimen | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 75 | 10 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 301, PASI 75 | 2 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 75 | 102 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 90 | 61 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 1, IGA mod 2009 0 or 1 | 70 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 50 | 142 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 75 | 91 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 25, PASI 90 | 42 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 25, IGA mod 2009 0 or 1 | 48 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 50 | 100 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 75 | 66 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Ext. week 73, IGA mod 2009 | 35 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 301, PASI 50 | 3 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 301, PASI 90 | 1 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 301, IGA mod 2009 | 1 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 1, PASI 50 | 163 Number of participants |
| Open-label | Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response | Extension week 73, PASI 90 | 31 Number of participants |