Hidradenitis Suppurativa
Conditions
Keywords
acne inversa, Hidradenitis suppurativa, maladie de Verneuil, inflammatory disease, AIN457, AIN457M, secukinumab, HS, lumps, skin, lesions
Brief summary
The purpose of this study was to demonstrate superiority of secukinumab at Week 16, based on Hidradenitis Suppurativa Clinical Response (HiSCR) rates versus placebo, along with the maintenance of efficacy of secukinumab at Week 52 in subjects with moderate to severe HS. Moreover, this study also assessed the safety and tolerability of secukinumab.
Detailed description
This was a multicenter, randomized, double-blind, placebo-controlled, parallel group study with two secukinumab dose regimens in 541 patients with moderate to severe HS. The study consisted of: screening (up to 4 weeks) treatment period 1 (16 weeks, active drug or placebo) and treatment period 2 (up to 1 year all patients on active drug); there was an optional extension study (NCT04179175). Adult males and females with moderate to severe HS were included, with a diagnosis of HS greater than 1 year prior to baseline. Dosing was once every 2 weeks, or once every 4 weeks via pre-filled syringe; periodic home-dosing is included. In Treatment Period 1, participants were randomized to secukinumab Q2W, secukinumab Q4W, placebo Q2W or placebo Q4W in 1:1:0.5:0.5 ratio. In Treatment Period 2, at the Week 16 visit participants initially randomized to placebo were switched to one of the two active dose regimens (secukinumab Q2W or Q4W), while subjects randomized to secukinumab during Treatment Period 1 continued on the same dose. At the Week 16 visit, subjects initially randomized to placebo were switched to one of the two active dose regimens (secukinumab Q2W or Q4W), while subjects randomized to secukinumab during Treatment Period 1 continued on the same dose. The primary objective was to demonstrate the efficacy of secukinumab compared to placebo with respect to HISCR after 16 weeks of treatment; secondary objectives were to assess difference in proportion of patients with HS flares, and proportion of patients with clinical response in HS related skin pain after 16 weeks of treatment. Key safety data was collected, along with Patient Reported Outcomes.
Interventions
DRUGsecukinumab
Secukinumab 300mg every 2 or every 4 weeks
DRUGPlacebo
Placebo 300mg every 2 or every 4 weeks
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This was a Multicenter, randomized, double-blind, placebo-controlled, parallel group study, with two secukinumab dose regimens in 541 patients with moderate to severe HS.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. * Male and female patients ≥ 18 years of age. * Diagnosis of HS ≥ 1 year prior to baseline. * Patients with moderate to severe HS defined as: * A total of at least 5 inflammatory lesions, i.e. abscesses and/or inflammatory nodules AND * Inflammatory lesions should affect at least 2 distinct anatomic areas * Patients agree to daily use of topical over-the-counter antiseptics on the areas affected by HS lesions while on study treatment.
Exclusion criteria
* Total fistulae count ≥ 20 at baseline. * Any other active skin disease or condition that may interfere with assessment of HS. * Active ongoing inflammatory diseases other than HS that require treatment with prohibited medications. * Use or planned use of prohibited treatment. Washout periods detailed in the protocol have to be adhered to. * History of hypersensitivity to any of the study drug constituents. * 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). * Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50) | 16 weeks | HiSCR50 at Week 16 is defined as at least a 50% decrease in Abscess and inflammatory Nodule (AN) count compared to baseline with no increase in the number of abscesses and/or in the number of draining fistulas from baseline to Week 16. The baseline is defined as the last assessment (including unscheduled visits) obtained before/on the day of the first administration of the study treatment, or on the randomization date if there had been no drug administration. This endpoint was analyzed by logistic regression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in AN50 Count at Week 16 | Baseline, 16 weeks | The HS affected areas, e.g. right and left axillary (armpit), right and left gluteal (buttock), right and left inguinal-femoral (groin), perineal, pubic, sternal, right and left sub-mammary (breast) and others were assessed by the physician for abscesses, inflammatory nodules, draining fistulas, total fistulas, and other lesions. Inflammatory lesions, including abscesses, nodules, draining fistulae, total fistulae and other lesions were counted. The analysis method for percentage change from baseline in abscesses and inflammatory nodules (AN) count at Week 16 was an ANCOVA model. |
| Percentage of Participants With Hidradenitis Suppurativa (HS) Flares | 16 weeks | Percentage of participants who experience at least one flare over 16 weeks. A flare is defined as at least a 25% increase in abscesses and inflammatory nodules (AN) count with a minimum increase of 2 AN relative to baseline. This endpoint was analyzed by logistic regression. |
| Percentage of Participants Achieving NRS30 | Baseline, week 16 | Patients achieving Numerical Rating Scale score of 30 (NRS30) at week 16, defined as at least a 30% reduction and at least one unit reduction from baseline in the Patient's Global assessment of Skin Pain (where range 0 \[no skin pain\] to 10 \[worst skin pain\]). This endpoint was analyzed by logistic regression. |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Philippines, Poland, Portugal, Russia, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Participants were enrolled in 111 study sites worldwide.
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 1 - Q2W Secukinumab 300mg every 2 weeks | 181 |
| Secukinumab 2 - Q4W Secukinumab 300mg every 4 weeks | 180 |
| Placebo Placebo group to secukinumab 300mg every 4 weeks | 180 |
| Total | 541 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Treatment Period 1 (Until Week 16) | Adverse Event | 4 | 0 | 1 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Lost to Follow-up | 3 | 1 | 1 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Misrandomized | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Physician Decision | 1 | 1 | 1 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Severe GCP Violation | 1 | 1 | 0 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Technical problems | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (Until Week 16) | Withdrawal by Subject | 4 | 9 | 5 | 0 | 0 |
| Treatment Period 2 (After Week 16) | Adverse Event | 6 | 5 | 0 | 1 | 2 |
| Treatment Period 2 (After Week 16) | Lost to Follow-up | 3 | 3 | 0 | 2 | 2 |
| Treatment Period 2 (After Week 16) | Physician Decision | 0 | 2 | 0 | 1 | 1 |
| Treatment Period 2 (After Week 16) | Poor efficacy | 1 | 2 | 0 | 2 | 1 |
| Treatment Period 2 (After Week 16) | Pregnancy | 1 | 0 | 0 | 1 | 0 |
| Treatment Period 2 (After Week 16) | Withdrawal by Subject | 26 | 20 | 0 | 10 | 6 |
Baseline characteristics
| Characteristic | Secukinumab 1 - Q2W | Secukinumab 2 - Q4W | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 178 Participants | 177 Participants | 179 Participants | 534 Participants |
| Age, Continuous | 37.1 years STANDARD_DEVIATION 12.53 | 35.7 years STANDARD_DEVIATION 11.71 | 35.5 years STANDARD_DEVIATION 10.75 | 36.1 years STANDARD_DEVIATION 11.69 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 19 Participants | 23 Participants | 24 Participants | 66 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 10 Participants | 12 Participants | 37 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 145 Participants | 146 Participants | 139 Participants | 430 Participants |
| Sex: Female, Male Female | 102 Participants | 100 Participants | 102 Participants | 304 Participants |
| Sex: Female, Male Male | 79 Participants | 80 Participants | 78 Participants | 237 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 181 | 0 / 180 | 0 / 180 | 0 / 266 | 0 / 267 | 0 / 533 |
| other Total, other adverse events | 135 / 181 | 132 / 180 | 88 / 180 | 184 / 266 | 183 / 267 | 367 / 533 |
| serious Total, serious adverse events | 13 / 181 | 9 / 180 | 6 / 180 | 18 / 266 | 19 / 267 | 37 / 533 |
Outcome results
Primary
Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50)
HiSCR50 at Week 16 is defined as at least a 50% decrease in Abscess and inflammatory Nodule (AN) count compared to baseline with no increase in the number of abscesses and/or in the number of draining fistulas from baseline to Week 16. The baseline is defined as the last assessment (including unscheduled visits) obtained before/on the day of the first administration of the study treatment, or on the randomization date if there had been no drug administration. This endpoint was analyzed by logistic regression.
Time frame: 16 weeks
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 1 - Q2W | Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50) | 45.0 Percentage of participants |
| Secukinumab 2 - Q4W | Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50) | 41.8 Percentage of participants |
| Placebo | Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50) | 33.7 Percentage of participants |
Comparison: Logistic regression analysis of HiSCR50 response at Week 16 (multiple imputation)p-value: 0.00795% CI: [1.12, 2.73]Regression, Logistic
Comparison: Logistic regression analysis of HiSCR50 response at Week 16 (multiple imputation)p-value: 0.041895% CI: [0.95, 2.32]Regression, Logistic
Secondary
Percentage Change From Baseline in AN50 Count at Week 16
The HS affected areas, e.g. right and left axillary (armpit), right and left gluteal (buttock), right and left inguinal-femoral (groin), perineal, pubic, sternal, right and left sub-mammary (breast) and others were assessed by the physician for abscesses, inflammatory nodules, draining fistulas, total fistulas, and other lesions. Inflammatory lesions, including abscesses, nodules, draining fistulae, total fistulae and other lesions were counted. The analysis method for percentage change from baseline in abscesses and inflammatory nodules (AN) count at Week 16 was an ANCOVA model.
Time frame: Baseline, 16 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Secukinumab 1 - Q2W | Percentage Change From Baseline in AN50 Count at Week 16 | -46.8 percentage change from baseline | Standard Error 3.33 |
| Secukinumab 2 - Q4W | Percentage Change From Baseline in AN50 Count at Week 16 | -42.4 percentage change from baseline | Standard Error 4.01 |
| Placebo | Percentage Change From Baseline in AN50 Count at Week 16 | -24.3 percentage change from baseline | Standard Error 4.33 |
Comparison: Analysis of covariance of percentage change from baseline in AN count at Week 16 (multiple imputation)p-value: <0.000195% CI: [-33.9, -12.21]ANCOVA
Comparison: Analysis of covariance of percentage change from baseline in AN count at Week 16 (multiple imputation)p-value: 0.000495% CI: [-29.32, -7.6]ANCOVA
Secondary
Percentage of Participants Achieving NRS30
Patients achieving Numerical Rating Scale score of 30 (NRS30) at week 16, defined as at least a 30% reduction and at least one unit reduction from baseline in the Patient's Global assessment of Skin Pain (where range 0 \[no skin pain\] to 10 \[worst skin pain\]). This endpoint was analyzed by logistic regression.
Time frame: Baseline, week 16
Population: FAS restricted to participants with baseline NRS score greater or equal to 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 1 - Q2W | Percentage of Participants Achieving NRS30 | 34.1 Percentage of participants |
| Secukinumab 2 - Q4W | Percentage of Participants Achieving NRS30 | 32.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving NRS30 | 23.8 Percentage of participants |
Comparison: Logistic regression analysis of skin pain/NRS30 response at Week 16 (pooled data, multiple imputation)p-value: 0.024895% CI: [1, 3.4]Regression, Logistic
Comparison: Logistic regression analysis of skin pain/NRS30 response at Week 16 (pooled data, multiple imputation)p-value: 0.004495% CI: [1.15, 2]Regression, Logistic
Secondary
Percentage of Participants With Hidradenitis Suppurativa (HS) Flares
Percentage of participants who experience at least one flare over 16 weeks. A flare is defined as at least a 25% increase in abscesses and inflammatory nodules (AN) count with a minimum increase of 2 AN relative to baseline. This endpoint was analyzed by logistic regression.
Time frame: 16 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Secukinumab 1 - Q2W | Percentage of Participants With Hidradenitis Suppurativa (HS) Flares | 15.4 Percentage of participants |
| Secukinumab 2 - Q4W | Percentage of Participants With Hidradenitis Suppurativa (HS) Flares | 23.2 Percentage of participants |
| Placebo | Percentage of Participants With Hidradenitis Suppurativa (HS) Flares | 29.0 Percentage of participants |
Comparison: Logistic regression analysis of Flare over 16 weeks (multiple imputation)p-value: 0.00195% CI: [0.25, 0.73]Regression, Logistic
Comparison: Logistic regression analysis of Flare over 16 weeks (multiple imputation)p-value: 0.092695% CI: [0.43, 1.17]Regression, Logistic