Chronic Plaque-type Psoriasis
Conditions
Keywords
Moderate to severe chronic plaque-type psoriasis, AIN457, dermatology
Brief summary
The purpose of the study is to determine whether, in patients with moderate to severe plaque-type psoriasis, AIN457 administered subcutaneously reduces the severity of psoriasis symptoms and the extent to which the patient's body area is affected by the disease (compared to placebo).
Interventions
DRUGAIN457
DRUGAIN457A
Induction with monthly injections - Monthly: secukinumab (AIN457) 150 mg s.c. administered at weeks 1, 5, 9
DRUGPlacebo
Placebo - Placebo: Placebo administered at weeks 1, 2, 3, 5, 9
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
* Men or women at least 18 years of age at time of consent * Chronic plaque-type psoriasis diagnosed for at least 6 months at time of randomization * At time of randomization, moderate to severe psoriasis as defined by: * PASI score of 12 or greater and * IGA score of 3 or greater and * Body Surface Area (BSA) affected by plaque-type psoriasis of 10 % or greater * At screening and randomization, chronic plaque-type psoriasis considered inadequately controlled by: * topical treatment and/or * phototherapy and/or * previous systemic therapy
Exclusion criteria
* Patients meeting any of the following criteria will be excluded from entry into the study: * Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at screening or randomization * Drug-induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) and randomization * Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids, UV therapy) at randomization. Washout periods detailed in the study protocol have to be adhered to * Ongoing use of other prohibited treatments at randomization. Washout periods detailed in the study protocol have to be adhered to. All prior concomitant medications must be on a stable dose for at least four weeks before study drug administration * Known immunosuppression (e.g., AIDS) at screening and / or randomization * History or evidence of active tuberculosis at screening. All patients will be tested for tuberculosis status using a blood test (QuantiFERON®-TB Gold In-Tube). Patients with evidence of latent tuberculosis may enter the trial after sufficient treatment has been initiated according to local regulations. * Active systemic infections (other than common cold) during the two weeks before randomization (e.g., hepatitis) * At screening, history or symptoms of malignancy of any organ system (other than history of basal cell carcinoma and / or up to three squamous cell carcinomas of the skin, if successful treatment has been performed, with no signs of recurrence; actinic keratoses, if present at screening, should be treated according to standard therapy before randomization), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases * History of congestive heart failure (NYHA functional classification ≥III) at screening and / or randomization * History of severe hypersensitivity to any human or humanized biological agents (antibody or soluble receptor) at screening and / or randomization * Any severe, progressive or uncontrolled medical condition at randomization that in the judgment of the investigator prevents the patient from participating in the study * Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | 13 weeks | Number (%) of patients achieving PASI 50, PASI 75, PASI 90, by visit and induction treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | week 21 to 29 | — |
| The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 13 weeks | The investigator's global assessment (IGA) was used to evaluate overall psoriatic disease, with scores ranging from 0 (clear) to 5 (very severe disease). Treatment success was defined as patients who achieved IGA 0 or 1 and improvement of at least 2 points on the IGA scale compared to baseline. The IGA rating score for involvement of hands and feet ranged from 0 (clear) to 4 (severe). |
Countries
France, Germany, Iceland, Israel, Japan, Norway, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Induction Single Dose Baseline through Week 12 | 66 |
| Induction Monthly Dose | 138 |
| Induction Early Loading Dose | 133 |
| Placebo | 67 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Induction Period | Adminstative Problems | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Induction Period | Adverse Event | 1 | 0 | 3 | 2 | 0 | 0 | 0 |
| Induction Period | Lack of Efficacy | 2 | 1 | 0 | 5 | 0 | 0 | 0 |
| Induction Period | Withdrawal by Subject | 1 | 2 | 2 | 2 | 0 | 0 | 0 |
| Maintenance Period | Administrative Problems | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Maintenance Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 8 |
| Maintenance Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 13 |
| Maintenance Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 2 | 7 |
| Maintenance Period | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Maintenance Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 6 | 2 | 13 |
Baseline characteristics
| Characteristic | Induction Single Dose | Total | Placebo | Induction Early Loading Dose | Induction Monthly Dose |
|---|---|---|---|---|---|
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 11.32 | 44.1 Years STANDARD_DEVIATION 12.44 | 44.2 Years STANDARD_DEVIATION 12.59 | 44.5 Years STANDARD_DEVIATION 12.45 | 44.2 Years STANDARD_DEVIATION 12.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 46 Participants | 8 Participants | 14 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 353 Participants | 56 Participants | 118 Participants | 120 Participants |
| Sex: Female, Male Female | 13 Participants | 98 Participants | 23 Participants | 28 Participants | 34 Participants |
| Sex: Female, Male Male | 53 Participants | 306 Participants | 44 Participants | 105 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 66 | 53 / 138 | 46 / 133 | 29 / 67 | 16 / 65 | 16 / 67 | 83 / 247 | 3 / 17 | 4 / 15 | 5 / 72 |
| serious Total, serious adverse events | 3 / 66 | 3 / 138 | 6 / 133 | 1 / 67 | 4 / 65 | 2 / 67 | 12 / 247 | 0 / 17 | 0 / 15 | 5 / 72 |
Outcome results
Primary
The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo.
Number (%) of patients achieving PASI 50, PASI 75, PASI 90, by visit and induction treatment
Time frame: 13 weeks
Population: (Full analysis set, LOCF) Number (%) of patients achieving PASI 50, PASI 75, PASI 90, by visit and induction treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 90 | 2 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 50 | 18 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 75 | 7 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 75 | 58 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 90 | 24 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 50 | 83 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 50 | 101 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 75 | 72 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 90 | 42 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 50 | 7 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 90 | 1 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque-type Psoriasis With Respect to PASI 75 Achievement After 12 Weeks of Treatment, Compared to Placebo. | PASI 75 | 1 Participants achieving goal |
Secondary
The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo
The investigator's global assessment (IGA) was used to evaluate overall psoriatic disease, with scores ranging from 0 (clear) to 5 (very severe disease). Treatment success was defined as patients who achieved IGA 0 or 1 and improvement of at least 2 points on the IGA scale compared to baseline. The IGA rating score for involvement of hands and feet ranged from 0 (clear) to 4 (severe).
Time frame: 13 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 1= almost clear | 3 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 4=severe disease | 15 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 0=clear | 0 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 2= mild disease | 17 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 3= moderate disease | 28 Participants achieving goal |
| Induction Single Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 5= very serious disease | 3 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 3= moderate disease | 44 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 2= mild disease | 42 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 4=severe disease | 18 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 0=clear | 2 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 5= very serious disease | 2 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 1= almost clear | 29 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 3= moderate disease | 33 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 1= almost clear | 32 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 4=severe disease | 12 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 0=clear | 17 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 2= mild disease | 38 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 5= very serious disease | 0 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 2= mild disease | 3 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 0=clear | 1 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 5= very serious disease | 7 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 4=severe disease | 29 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 3= moderate disease | 26 Participants achieving goal |
| Placebo Dose | The Efficacy of Three Induction Regimens of AIN457 Administered Subcutaneously With Respect Participants Who Reported Either an IGA 0 or 1 After 12 Weeks of Treatment, Compared to Placebo | 1= almost clear | 0 Participants achieving goal |
Secondary
The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29
Time frame: week 21 to 29
Population: (Full analysis set, LOCF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Single Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 75 | 55 Participants achieving goal |
| Induction Single Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 50 | 64 Participants achieving goal |
| Induction Single Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 90 | 38 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 75 | 45 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 50 | 60 Participants achieving goal |
| Induction Monthly Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 90 | 14 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 50 | 200 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 90 | 53 Participants achieving goal |
| Induction Early Loading Dose | The Efficacy of Two Maintenance Regimens of AIN457 With Respect to PASI 75 Achievement at Least Once From Week 21 to 29 | PASI 75 | 114 Participants achieving goal |