Moderate to Severe Chronic Plaque-type Psoriasis
Conditions
Keywords
psoriasis, secukinumab, immune-mediated systemic disease, papules, plaques, itching, weight
Brief summary
The purpose of this study is to assess secukinumab high dose (every 2 weeks) vs standard dose (every 4 weeks) in heavy body weight subjects with moderate to severe plaque psoriasis.
Detailed description
A 52-week multicenter, randomized, double-blind, parallel-group trial in 331 subjects with moderate to severe chronic plaque-type psoriasis of body weight 90 kg or higher at time of randomization. This study consisted of 4 periods: screening (up to 4 weeks), treatment Period 1 (16 weeks), treatment Period 2 (36 weeks), and post-treatment follow-up (8 weeks). Subjects were randomized using a 1:1 ratio to the following groups: Secukinumab 300 mg every 2 weeks; Secukinumab 300 mg every 4 weeks. In addition, subjects from the 300 mg every 4 weeks group who did not achieve Psoriasis Area Severity Index (PASI) 90 response at Week 16 were reassigned using a 1:1 ratio to either remain on secukinumab 300 mg every 4 weeks or receive secukinumab 300 mg every 2 weeks starting at Week 16, until the end of treatment.
Interventions
sub-cutaneous secukinumab prefilled syringe 150 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Written informed consent must have been obtained before any assessment was performed. Where relevant, a legal representative will also have signed the informed study consent according to local laws and regulations. * Subjects must have been able to understand and communicate with the investigator and comply with the requirements of the study. * Men or women at least 18 years of age at time of screening. * Body weight of ≥ 90 kg at the time of randomization. * Chronic plaque-type psoriasis present for at least 6 months and diagnosed before randomization. * Moderate to severe psoriasis as defined at randomization by: * Psoriasis Area and Severity Index (PASI) score of 12 or greater, and * Investigator's Global Assessment (IGA) mod 2011 score of 3 or greater (based on a static scale of 0 - 4), and * Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater. * Candidate for systemic therapy. This is defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by: * topical treatment and/or, * phototherapy and/or, * previous systemic therapy. Key
Exclusion criteria
* Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at screening or Randomization. * Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be adhered to. Subjects not willing to limit ultraviolet (UV) light exposure (e.g., sunbathing and / or the use of tanning devices) during the course of the study will be considered not eligible for this study since UV light exposure is prohibited. Note: administration of live vaccines 6 weeks prior to Randomization or during the study period is also prohibited. * Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting Interleukin-17 (IL-17) or the IL-17 receptor. * Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 4 weeks until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations. * Pregnant or nursing (lactating) women * History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed). * History of hypersensitivity to any of the study drug constituents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set) | 16 weeks | A subject was considered as a PASI 90 responder if s/he achieved a reduction of 90% or more of the PASI score, compared to baseline, at a given time point.The head, trunk, upper limbs and lower limbs were assessed separately for erythema, thickening, and scaling. PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a theoretic maximum of 72.0, i.e., higher scores represent more severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set) | 16 weeks | IGA mod 2011 was conducted for overall psoriatic disease. The IGA modified 2011 used in this study was static, i.e., it referred exclusively to the subject's disease state at the time of the assessments, and did not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit. The scale has 0 (clear) as min and 4 (severe) as max, i.e., a higher score indicates more severity. |
| Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Adverse events were reported from first dose of study treatment until end of study treatment plus 8 weeks post treatment, up to a maximum timeframe of 470 days. | An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. |
Countries
Canada, Czechia, Germany, Hungary, Italy, Russia, United States
Participant flow
Pre-assignment details
331 participants in the study were randomized and 330 participants were treated. (One participant in the Secukinumab 300 mg Q4W arm was randomized but not treated. This participant was included in the randomization (demographic and disposition) set and the full analysis set, but was not included in the safety (Adverse Events) set.)
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 300 mg Every 2 Weeks (Q2W) 2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter every 2 weeks. Subjects remained on secukinumab 300 mg every 2 weeks until the end of treatment. | 165 |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (Safety) 2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter Q4W. Includes both subjects randomized to remain on Q4W the entire treatment period, and subjects that were Psoriasis Area and Severity Index (PASI) 90 responders at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group. | 135 |
| Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) 2 injections of secukinumab 150 mg once weekly up to week 4, then Q4W up to Week 16 and thereafter Q2W. Includes Psoriasis Area and Severity Index (PASI) 90 non-responders (NR) at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group (subjects randomized to switch to Q2W if PASI 90 non-responder at Week 16). | 31 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 8 | 2 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 | 0 |
| Overall Study | New therapy for study indication | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 5 | 1 |
| Overall Study | Withdrawal of informed consent | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Secukinumab 300 mg Every 2 Weeks (Q2W) | Secukinumab 300 mg Every 4 Weeks (Q4W) (Safety) | Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) | Total |
|---|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 12.73 | 46.1 years STANDARD_DEVIATION 13.24 | 44.7 years STANDARD_DEVIATION 13.61 | 47.1 years STANDARD_DEVIATION 13.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 151 Participants | 125 Participants | 30 Participants | 306 Participants |
| Sex: Female, Male Female | 39 Participants | 34 Participants | 10 Participants | 83 Participants |
| Sex: Female, Male Male | 126 Participants | 101 Participants | 21 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 165 | 1 / 134 | 0 / 31 | 1 / 330 |
| other Total, other adverse events | 66 / 165 | 57 / 134 | 16 / 31 | 139 / 330 |
| serious Total, serious adverse events | 14 / 165 | 18 / 134 | 4 / 31 | 36 / 330 |
Outcome results
Primary
Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set)
A subject was considered as a PASI 90 responder if s/he achieved a reduction of 90% or more of the PASI score, compared to baseline, at a given time point.The head, trunk, upper limbs and lower limbs were assessed separately for erythema, thickening, and scaling. PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a theoretic maximum of 72.0, i.e., higher scores represent more severity.
Time frame: 16 weeks
Population: Full analysis set. Please note that the Secukinumab 300 mg every 4 weeks non-responders up-titration (Q4W NR up) arm did not apply to this efficacy outcome measure and therefore no results are reported here for this arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set) | 121 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set) | 92 Participants |
p-value: 0.000395% CI: [7.45, 27.98]Regression, Logistic
p-value: 0.000395% CI: [1.44, 3.78]Regression, Logistic
Secondary
Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set)
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 8 weeks post treatment, up to a maximum timeframe of 470 days.
Population: safety set - includes the results for the Secukinumab 300 mg every 4 weeks non-responders up-titration (Q4W NR up) arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with any AE(s) | 127 Participants |
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Death | 0 Participants |
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Non-fatal SAE(s) | 14 Participants |
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Discontinued study treatment due to any AE(s) | 4 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Discontinued study treatment due to any AE(s) | 9 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with any AE(s) | 97 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Non-fatal SAE(s) | 17 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Death | 1 Participants |
| Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Discontinued study treatment due to any AE(s) | 2 Participants |
| Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Death | 0 Participants |
| Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with serious or other significant events - Non-fatal SAE(s) | 4 Participants |
| Secukinumab 300 mg Every 4 Weeks Non-responders Up-titration (Q4W NR up) | Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set) | Patients with any AE(s) | 24 Participants |
Secondary
Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set)
IGA mod 2011 was conducted for overall psoriatic disease. The IGA modified 2011 used in this study was static, i.e., it referred exclusively to the subject's disease state at the time of the assessments, and did not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit. The scale has 0 (clear) as min and 4 (severe) as max, i.e., a higher score indicates more severity.
Time frame: 16 weeks
Population: Full analysis set. Please note that the Secukinumab 300 mg every 4 weeks non-responders up-titration (Q4W NR up) arm did not apply to this efficacy outcome measure and therefore no results are reported here for this arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab 300 mg Every 2 Weeks (Q2W) | Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set) | 122 Participants |
| Secukinumab 300 mg Every 4 Weeks (Q4W) (up to Week 16 Pre-dose) | Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set) | 109 Participants |
p-value: 0.049895% CI: [-1.65, 18.2]Regression, Logistic
p-value: 0.049895% CI: [0.92, 2.47]Regression, Logistic