Moderate to Severe Hidradenitis Suppurativa

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study with two secukinumab dose regimens in approximately 541 patients with moderate to severe HS. The study consists 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 will be an optional extension study. Adult males and females with moderate to severe HS will be included, with a diagnosis of HS greater than 1 year prior to baseline. Dosing will be once every 2 weeks, or once every 4 weeks via pre-filled syringe; periodic home-dosing is included The primary objective is to demonstrate the efficacy of secukinumab compared to placebo with respect to HISCR after 16 weeks of treatment; primary secondary objectives are 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 will be collected, along with Patient Reported Outcomes

Cosentyx

AIN457 (Secukinumab)
Inclisiran sodium

Solution for Injection
Solution for injection in pre-filled syringe (PFS)

300mg
300 mg/2 mL

Primary Outcome Measures :
Proportion of participants with Hidradenitis Suppurativa clinical response (HiSCR) [ Time Frame: 16 weeks ]
HiSCR is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and/or in the number of draining fistulae.


Secondary Outcome Measures :
Proportion of patients with Hidradenitis Suppurativa (HS) flares [ Time Frame: 16 weeks ]
Patients who experience at least one flare over 16 weeks, flare defined as at least a 25% increase in abscesses and inflammatory nodules (AN) count with a minimum increase of 2 AN relative to baseline

Participants achieving NRS30 [ Time Frame: 16 weeks ]
HS-related skin pain 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])

Percentage change in AN count [ Time Frame: 16 weeks ]
Percent change in abscesses and inflammatory nodules (AN) count

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female patients ≥ 18 years of age.
3. Diagnosis of HS ≥ 1 year prior to baseline.
4. 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
5. Patients agree to daily use of topical over-the-counter antiseptics on the areas affected by
HS lesions while on study treatment.

1. Total fistulae count ≥ 20 at baseline.
2. Any other active skin disease or condition that may interfere with assessment of HS.
3. Active ongoing inflammatory diseases other than HS that require treatment with prohibited
medications (see Table 6-2).
4. Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic,
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the
opinion of the investigator significantly immunocompromises the patient and/or places the
patient at unacceptable risk for receiving an immunomodulatory therapy.
5. Current severe progressive or uncontrolled diseases which renders the patient unsuitable for
the trial or puts the patient at increased risk, including any medical or psychiatric condition
which, in the Investigator’s opinion, would preclude the participant from adhering to the
protocol or completing the study per protocol.
6. Use or planned use of prohibited treatment. Washout periods detailed in the protocol have
to be adhered to (see Table 6-2).
7. For patients enrolling in the non-antibiotic strata: use of systemic antibiotics for the
treatment of HS within 28 days before baseline.
For patients enrolling in the antibiotic strata: patients enter the study under concomitant
treatment with systemic antibiotics (as per protocol) on a stable dose (defined as a dose or
dose regimen that has not changed in the previous 28 days before baseline and is considered
unlikely to change at least for the first 16 weeks during the study).
8. History of hypersensitivity to any of the study drug constituents.
9. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting
IL-17 A/F or the IL-17 receptor.
10. History of chronic or recurrent systemic infections or active systemic infections during the
last two weeks (exception: common cold) prior to randomization.
11. Evidence of tuberculosis infection as defined by a positive QuantiFERON® TB-Gold test
(QFT) at screening. Patients with a positive or indeterminate QFT test may participate in
the study if a full tuberculosis work-up (according to local practice/guidelines) completed
within 12 weeks prior to randomization, establishes conclusively that the patient has no
evidence of active or latent tuberculosis.
12. Medical history record of infection with human immunodeficiency virus (HIV), hepatitis B
or C prior to randomization, except for hepatitis C successfully treated and cured.
13. 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).
14. History or evidence of ongoing alcohol or drug abuse, which in the opinion of the
investigator will prevent the patient from adhering to the protocol and completing the study.
15. Pregnant or lactating women.
16. Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using methods of contraception during the entire study
or longer if required by locally approved prescribing information (e.g. in European Union
(EU) 20 weeks).
Contraception methods include:
 Total abstinence, when this is in line with the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception.
 Female sterilization (have had surgical bilateral oophorectomy [with or without
hysterectomy], total hysterectomy or tubal ligation at least six weeks before taking
study treatment). In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow-up hormone level assessment.
 Male sterilization (at least 6 months prior to screening). The vasectomized male partner
should be the sole partner for that patient.
 Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps). For United Kingdom: with spermicidal
foam/gel/film/cream/vaginal suppository.
 Use of oral (estrogen and progesterone), injected or implanted hormonal methods of
contraception or other forms of hormonal contraception that have comparable efficacy
(failure rate <1%), for example hormone vaginal ring or transdermal hormone
contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).
In case of use of oral contraception, women should have been stable on the same pill for a
minimum of 3 months before taking study treatment.
In case local regulations deviate from the contraception methods listed above, local
regulations apply and will be described in the informed consent form (ICF).
Note: Women are considered post-menopausal and not of childbearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g.
age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least
six weeks prior to enrollment. In the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone level
assessment is she considered not of childbearing potential.
No additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.