Study of Efficacy and Safety of Two Secukinumab Dose Regimens in Subjects With Moderate to Severe Hidradenitis Suppurativa (HS)

Conditions

Hidradenitis Suppurativa

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 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 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.

Ingram JR, Wozniak MB, Passera A, Uhlmann L, Martinez AL, Bechara FG, Bender RH, McLeod LD, Martin S, Moreno SG, Marvel J, Ravichandran S, Kimball AB.

2025-11-01

10.1093/bjd/ljaf307

Secukinumab in the Treatment of Moderate‐to‐Severe Hidradenitis Suppurativa: Pooled Pharmacokinetics and Safety Results From the <scp>SUNSHINE</scp> and <scp>SUNRISE</scp> Phase 3 Studies

Afsáneh Alavi, Z. Reguiaï, Gregor B. E. Jemec, Alice B. Gottlieb, Magdalena B. Wozniak et al. (14 authors)

International Journal of Dermatology2025-08-211 citations

10.1111/ijd.70025

Assessing Long-Term Pain Reduction with Secukinumab in Moderate to Severe Hidradenitis Suppurativa: A Post Hoc Analysis of the SUNSHINE and SUNRISE Phase 3 Trials

John R Ingram, Jacek C. Szepietowski, Łukasz Matusiak, Georgios Kokolakis, Magdalena B. Wozniak et al. (14 authors)

Dermatology and Therapy2025-05-151 citations

10.1007/s13555-025-01426-x

Secukinumab efficacy in patients with hidradenitis suppurativa assessed by the International Hidradenitis Suppurativa Severity Score System (<scp>IHS4</scp>): A post hoc analysis of the <scp>SUNSHINE</scp> and <scp>SUNRISE</scp> trials

Christos C. Zouboulis, Αthanassios Kyrgidis, Afsáneh Alavi, Gregor B. E. Jemec, Antonio Martorell et al. (16 authors)

Journal of the European Academy of Dermatology and Venereology2024-10-196 citations

10.1111/jdv.20369

New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the <scp>SUNSHINE</scp> and <scp>SUNRISE</scp> trials

Anna Passera, Elisa Muscianisi, David Demanse, Ginette A. Okoye, Gregor B. E. Jemec et al. (14 authors)

Journal of the European Academy of Dermatology and Venereology2024-08-058 citations

10.1111/jdv.20234

Secukinumab in Moderate to Severe Hidradenitis Suppurativa: Primary Endpoint Analysis From the SUNSHINE and SUNRISE Phase 3 Trials

Alexa B. Kimball, Afsáneh Alavi, Gregor B. E. Jemec, Alice B. Gottlieb, Xiaoling Wei et al. (12 authors)

SKIN The Journal of Cutaneous Medicine2023-03-138 citations

10.25251/skin.7.supp.129

Efficacy and Safety of Risankizumab for the Treatment of Hidradenitis Suppurativa: A Phase 2, Randomized, Placebo-Controlled Trial

Alexa B. Kimball, Errol P. Prens, Thierry Passeron, Emanual Maverakis, Irina Turchin et al. (11 authors)

Dermatology and Therapy2023-03-0952 citations

10.1007/s13555-023-00913-3

Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials.

Kimball AB, Jemec GBE, Alavi A, Reguiai Z, Gottlieb AB, Bechara FG, Paul C, Giamarellos Bourboulis EJ, Villani AP, Schwinn A, Ruëff F, Pillay Ramaya L, Reich A, Lobo I, Sinclair R, Passeron T, Martorell A, Mendes-Bastos P, Kokolakis G, Becherel PA, Wozniak MB, Martinez AL, Wei X, Uhlmann L, Passera A, Keefe D, Martin R, Field C, Chen L, Vandemeulebroecke M, Ravichandran S, Muscianisi E.

2023-02-03186 citations

10.1016/s0140-6736(23)00022-3

Interventions

DRUGSecukinumab

Secukinumab 300mg every 2 or every 4 weeks

DRUGPlacebo

Placebo 300mg every 2 or every 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

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 AN Count	Baseline, 16 weeks	Percent change from baseline in abscesses and inflammatory nodules (AN) count. This endpoint was analyzed by analysis of covariance.
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	16 weeks	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, Belgium, Bulgaria, Canada, Colombia, Croatia, Czechia, Denmark, France, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Lebanon, Lithuania, Malaysia, Netherlands, Philippines, Poland, Russia, Singapore, Slovakia, South Africa, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States, Vietnam

Participant flow

Pre-assignment details

Participants enrolled in 132 study sites worldwide.

Participants by arm

Arm	Count
AIN457 Q2W Secukinumab 300mg every 2 weeks	180
AIN457 Q4W Secukinumab 300mg every 4 weeks	180
Placebo Placebo group to secukinumab 300mg	183
Total	543

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Treatment Period 1 (Until Week 16)	Adverse Event	1	4	4	0	0
Treatment Period 1 (Until Week 16)	Lack of Efficacy	1	0	1	0	0
Treatment Period 1 (Until Week 16)	Lost to Follow-up	1	1	1	0	0
Treatment Period 1 (Until Week 16)	Misrandomized Subject	1	0	0	0	0
Treatment Period 1 (Until Week 16)	Pregnancy	0	0	1	0	0
Treatment Period 1 (Until Week 16)	Technical problems	1	0	1	0	0
Treatment Period 1 (Until Week 16)	Withdrawal by Subject	6	6	8	0	0
Treatment Period 2 (After Week 16)	Adverse Event	6	3	0	2	1
Treatment Period 2 (After Week 16)	Death	0	1	0	0	0
Treatment Period 2 (After Week 16)	Lack of Efficacy	3	3	0	1	2
Treatment Period 2 (After Week 16)	Lost to Follow-up	1	8	0	1	0
Treatment Period 2 (After Week 16)	Physician Decision	1	2	0	0	2
Treatment Period 2 (After Week 16)	Pregnancy	0	1	0	0	0
Treatment Period 2 (After Week 16)	Technical Problems	1	0	0	0	0
Treatment Period 2 (After Week 16)	Withdrawal by Subject	9	18	0	9	12

Baseline characteristics

Characteristic	AIN457 Q2W	AIN457 Q4W	Placebo	Total
Age, Continuous	37.3 Years STANDARD_DEVIATION 11.48	35.5 Years STANDARD_DEVIATION 11.41	36.2 Years STANDARD_DEVIATION 11.25	36.3 Years STANDARD_DEVIATION 11.38
Age, Customized >=65 years	3 participants	2 participants	2 participants	7 participants
Age, Customized Between 18 and 65 years	177 participants	178 participants	181 participants	536 participants
Race/Ethnicity, Customized American Indian or Alaska native	7 Participants	5 Participants	8 Participants	20 Participants
Race/Ethnicity, Customized Asian	16 Participants	16 Participants	19 Participants	51 Participants
Race/Ethnicity, Customized Black or African American	18 Participants	19 Participants	12 Participants	49 Participants
Race/Ethnicity, Customized Multiple	4 Participants	1 Participants	1 Participants	6 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Not Reported	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized White	133 Participants	139 Participants	143 Participants	415 Participants
Sex: Female, Male Female	98 Participants	103 Participants	105 Participants	306 Participants
Sex: Female, Male Male	82 Participants	77 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 / 180	1 / 180	0 / 183	0 / 261	2 / 266	2 / 527
other Total, other adverse events	123 / 180	125 / 180	84 / 183	174 / 261	174 / 266	348 / 527
serious Total, serious adverse events	19 / 180	15 / 180	5 / 183	22 / 261	23 / 266	45 / 527

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): consisted of all subjects to whom study treatment had been assigned, excluding mis-randomized patients.~Subjects were analyzed according to the treatment assigned at randomization.

Arm	Measure	Value (NUMBER)
AIN457 Q2W	Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50)	42.3 Percentage of Participants
AIN457 Q4W	Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50)	46.1 Percentage of Participants
Placebo	Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50)	31.2 Percentage of Participants

p-value: 0.014995% CI: [1.05, 2.55]Regression, Logistic

p-value: 0.002295% CI: [1.22, 2.96]Regression, Logistic

Secondary

Percentage Change From Baseline in AN Count

Percent change from baseline in abscesses and inflammatory nodules (AN) count. This endpoint was analyzed by analysis of covariance.

Time frame: Baseline, 16 weeks

Population: Full Analysis Set

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
AIN457 Q2W	Percentage Change From Baseline in AN Count	-39.3 Percentage change from baseline	Standard Error 4.43
AIN457 Q4W	Percentage Change From Baseline in AN Count	-45.5 Percentage change from baseline	Standard Error 4.08
Placebo	Percentage Change From Baseline in AN Count	-22.4 Percentage change from baseline	Standard Error 4.84

p-value: 0.005195% CI: [-28.79, -3.88]ANCOVA

p-value: 0.000195% CI: [-35.24, -10.63]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: 16 weeks

Population: Full Analysis Set restricted to participants with baseline NRS score greater or equal to 3

Arm	Measure	Value (NUMBER)
AIN457 Q2W	Percentage of Participants Achieving NRS30	38.6 Percentage of participants
AIN457 Q4W	Percentage of Participants Achieving NRS30	34.7 Percentage of participants
Placebo	Percentage of Participants Achieving NRS30	22.4 Percentage of participants

p-value: 0.002695% CI: [1.28, 4.09]Regression, Logistic

p-value: 0.020695% CI: [1.03, 3.37]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: Full Analysis Set

Arm	Measure	Value (NUMBER)
AIN457 Q2W	Percentage of Participants With Hidradenitis Suppurativa (HS) Flares	20.1 Percentage of Participants
AIN457 Q4W	Percentage of Participants With Hidradenitis Suppurativa (HS) Flares	15.6 Percentage of Participants
Placebo	Percentage of Participants With Hidradenitis Suppurativa (HS) Flares	27.0 Percentage of Participants

p-value: 0.073295% CI: [0.41, 1.14]Regression, Logistic

p-value: 0.004995% CI: [0.29, 0.84]Regression, Logistic

Study of Efficacy and Safety of Two Secukinumab Dose Regimens in Subjects With Moderate to Severe Hidradenitis Suppurativa (HS)

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With Hidradenitis Suppurativa Clinical Response (HiSCR50)

Percentage Change From Baseline in AN Count

Percentage of Participants Achieving NRS30

Percentage of Participants With Hidradenitis Suppurativa (HS) Flares