Hidradenitis Suppurativa (Acne Inversa), Hidradenitis Suppurativa (HS), Secukinumab
Conditions
Brief summary
Secukinumab is currently approved in Europe, US and China for the treatment of moderate to severe HS as a biologic agent targeting IL-17A.Two phase III clinical trials (SUNSHINE and SUNRISE) showed that 300 mg s.c. every 2 weeks resulted in 42% to 45% of patients achieving a clinical response (HiSCR) to HS, and the efficacy was sustained through 52 weeks.However, we found in clinical practice that some HS patients present with localized lesions (small areas of involvement, affecting only 1-2 anatomic areas) that are resistant to conventional therapy, and have not yet fulfilled surgical indications, and the need for systemic biologic therapy is controversial.Such patients often experience inadequate response or slow onset of action when they receive secukinumab by routine subcutaneous injection - possibly related to inadequate drug concentration in the focal lesional area and limited local anti-inflammatory effects after systemic administration.In addition, side effects of conventional subcutaneous injection system are greater, and the application is limited in some patients, so it is necessary to explore more appropriate and safer drug delivery method for localized skin lesions.Localized HS, local injection of lesions may enhance anti-inflammatory effects while reducing systemic exposure by increasing drug concentrations at the lesion site.Therefore, exploring novel modes of administration of secukinumab has practical clinical implications based on clinical practice needs and the context of the previous literature.In summary, by exploring the efficacy and safety of local skin injection of secukinumab, this study may provide a new strategy for the treatment of limited HS with sufficient scientific rationale and significant potential benefits and manageable risks.
Detailed description
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses, sinus tracts, and scarring, with a global prevalence of about 1%, occurring in apocrine gland-rich areas such as the axillae and groin. Its pathogenesis is closely related to hair follicle obstruction, dysbacteriosis and immune disorders, in which IL-17A-mediated inflammatory pathways have been demonstrated to be the core driver - IL-17A levels are significantly increased in HS lesions, which can promote neutrophil infiltration and abscess formation. Secukinumab is currently approved in Europe, US and China for the treatment of moderate to severe HS as a biologic agent targeting IL-17A.Two phase III clinical trials (SUNSHINE and SUNRISE) showed that 300 mg s.c. every 2 weeks resulted in 42% to 45% of patients achieving a clinical response (HiSCR) to HS, and the efficacy was sustained through 52 weeks.However, we found in clinical practice that some HS patients present with localized lesions (small areas of involvement, affecting only 1-2 anatomic areas) that are resistant to conventional therapy, and have not yet fulfilled surgical indications, and the need for systemic biologic therapy is controversial.Such patients often experience inadequate response or slow onset of action when they receive secukinumab by routine subcutaneous injection - possibly related to inadequate drug concentration in the focal lesional area and limited local anti-inflammatory effects after systemic administration.In addition, side effects of conventional subcutaneous injection system are greater, and the application is limited in some patients, so it is necessary to explore more appropriate and safer drug delivery method for localized skin lesions.The successful experience of topical injection of biologics in psoriasis provides an important reference for clinical practice, such as study of nail psoriasis showed that intralesional secukinumab significantly increased local drug concentrations with 73.2% improvement in nail lesions and good safety.This suggests that for localized HS, local injection of lesions may enhance anti-inflammatory effects while reducing systemic exposure by increasing drug concentrations at the lesion site.Therefore, exploring novel modes of administration of secukinumab has practical clinical implications based on clinical practice needs and the context of the previous literature.In summary, by exploring the efficacy and safety of local skin injection of secukinumab, this study may provide a new strategy for the treatment of limited HS with sufficient scientific rationale and significant potential benefits and manageable risks.
Interventions
OTHERTopical injection of Secukinmab
Topical injection of Secukinmab
DRUGSubcutaneous injection of Secukinumab
Subcutaneous injection of Secukinumab
Sponsors
Peking Union Medical College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Meet international diagnostic criteria for hidradenitis suppurativa 2. Aged ≥ 18 years 3. Disease duration ≥ 6 months and resistance to conventional therapy (no significant improvement for ≥ 3 months) 4. Lesions were confined to a single anatomical area 5. Voluntarily signed the informed consent form and was able to cooperate in all visits and examinations.
Exclusion criteria
1. Hypersensitivity to any component of secukinumab injection 2. With severe vital organ failure 3. With active infection or malignancy (malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin and cured) 4. Treatment with biologics, immunosuppressants, or systemic corticosteroids within the last 3 months 5. Pregnant, nursing, or planning conception during the study 6. Mental disorders or cognitive impairment that precludes understanding of study procedures 7. Participating in another clinical study and are at risk of an interaction between the study drugs 8. Other conditions assessed by the investigators as inappropriate for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in International HS Severity Score System (IHS4) | Baseline (Day 1) and Week 24 | IHS4 score is calculated by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild disease, 4 to 10 signifies moderate disease, and 11 or higher signifies severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR)50 | At Week4、8、12、16、20、24 | HiSCR50 is defined as at least a 50% reduction in the total abscess and inflammatory nodule count, with no increase in abscess count and no increase in draining fistula count, relative to Baseline. |
| Change from baseline in pain measured by Visual analog scale (VAS) | Baseline (Day 1) and week4、8、12、16、20、24 | Visual analog scale (VAS) is a simple, 1-dimensional scale that measures pain intensity, typically represented as a 10-cm horizontal line with anchors such as no pain and worst possible pain. |
| Change from baseline in Dermatology Life Quality Index (DLQI) Total Score | Baseline (Day 1) and week4、8、12、16、20、24 | DLQI was a simple, compact, and practical questionnaire to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. The DLQI domains include symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The participant respond on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). The DLQI total score was derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. A lower score (that is, negative change score) indicated improvement in the Quality of Life. |
| Change from baseline in serum level of high-density C-reactive protein (hs-CRP) | Baseline (Day 1) and week4、8、12、16、20、24 | high-density C-reactive protein (hs-CRP), which is an acute phase protein (APP), is effective for evaluating the severity and degree of inflammation in patients with HS. A normal hs-CRP level is below 3.0 mg/L. A level between 3.1-10 mg/L is considered elevated. An hs-CRP level above 10 mg/ L is very high, more likely indicating an acute inflammatory event due to infection. |
| Change from baseline in erythrocyte sedimentation rate (ESR) | Baseline (Day 1) and week4、8、12、16、20、24 | ESR is an indirect acute phase reactant reflecting plasma viscosity and the presence of APP, especially fibrinogen. ESR is a marker of HS disease activity. A normal range for ESR depends on your age and sex: Males younger than 50, less than 15 millimeters per hour (\<15 mm/hr); males older than 50, \<20mm/hr; females younger than 50, \<20mm/hr; females older than 50, \<30mm/hr |
| Change from baseline in serum level of Interleukin-6 (IL-6) | Baseline (Day 1) and week4、8、12、16、20、24 | Level of serum IL-6 is considered as an inflammatory marker. The normal range of serum IL-6 lies between 0 to 1.8 pg/mL |
| Change from baseline in white blood cell count (WBC) | Baseline (Day 1) and week4、8、12、16、20、24 | A white blood cell count test measures the number of white blood cells in a sample of blood. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs), treatment related adverse events (TRAEs), serious adverse events (SAEs) and other safety indicators | From baseline (Day 1) to week24 | A SAE is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent disability/incapacity; Is a congenital anomaly/birth defect; Important medical events. TEAEs are defined as those AEs that have a start date on or following the first dose of study treatment. |
Countries
China
Contacts
Primary ContactJunyou ZHENG, Dr
Outcome results
None listed