A Phase 4, Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Assess the Safety and Efficacy of Adalimumab Used in Conjunction with Surgery in Subjects with Moderate to Severe Hidradenitis Suppurativa

Hidradenitis suppurativa (HS), also known as acne inversa is a chronic systemic
relapsing inflammatory disease primarily affecting the skin in intertriginous
areas, i.e., axillae, groin, and inframammary region. Hidradenitis suppurativa
is characterized by recurrent inflamed deep-seated acneiform nodules that
result in abscesses and chronic draining sinus tract formation leading to
scarring, disfigurement, and life-altering disability. Its negative impact on
quality of life is extreme, mainly due to the lack of early recognition,
accurate diagnosis, and appropriate management. HS has a profoundly negative
impact on patients* physical, social, and economic lives, with a higher
morbidity index than urticaria, neurofibromatosis, psoriasis, atopic
dermatitis, or alopecia. HS patients, mainly women, lose an average of 2-7 days
of work per year. HS creates a substantial burden of disease, particularly in
those subjects with more severe manifestations.

Prior to the Adalimumab Clinical Trial program, the only placebo-controlled
trial of HS demonstrated modest efficacy with the use of topical clindamycin.
Other treatments for HS include: medical treatment (e.g., systemic combination
therapy with clindamycin and rifampicin, intra-lesional triamcinolone),
surgical treatment (radical excision, marsupialization, and de-roofing), and
laser treatment (carbon dioxide [CO2] laser and neodymium-doped yttrium
aluminum garnet [Nd:YAG] laser). It is difficult to evaluate the efficacy for
these interventions because their use is described in open-label, frequently
retrospective, case series and case reports, with variable, but typically short
term follow-up.

Case series and case reports have shown that inhibitors of TNF-α are effective
in treating HS. Thus AbbVie conducted Phase 2 and Phase 3 clinical trials,
demonstrating the clinical efficacy and safety of adalimumab in subjects with
moderate to severe HS.

Adalimumab is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody
containing only human peptide sequences. Adalimumab binds with high affinity
and specificity to soluble TNF-α but not to lymphotoxin-α (TNF-β). TNF-α is a
naturally occurring cytokine that is involved in normal inflammatory and immune
responses. Elevated levels of TNF-α are thought to play an important role in
pathologic inflammation. Adalimumab binds specifically to TNF-α and neutralizes
the biological function of TNF-α by blocking its interaction with the p55 and
p75 cell surface TNF-α receptors. Adalimumab received approval in the EU for
treatment of active moderate to severe HS in 2015. Additional updates regarding
approved indications can be found in the current edition of the Humira Summary
of Product Characteristics (SmPC).

Patients undergoing surgery for HS lesions were not studied in the registration
trials; therefore there are no placebo-controlled data that inform the
physician regarding the impact of adalimumab on HS lesions in the patient who
is undergoing surgery as part of therapy to manage the disease. Based on the
medical need, AbbVie considers use of adalimumab in conjunction with surgery as
part of the treatment for moderate to severe HS, and further investigation is
warranted into the safety and efficacy of combined treatment.

Primary objective:
Assess the safety and efficacy of adalimumab prior to surgery in subjects with
moderate to severe HS who are surgical candidates.

Secondary objectives:
Assess the impact of adalimumab on the planned HS surgical site before surgery,
evaluate the safety and efficacy of adalimumab when used after surgery,
evaluate Patient Reported Outcomes (PRO) related to health status, HS-related
symptoms (e.g., drainage, swollen skin), physical functioning, treatment
satisfaction, and work/activity impairment. The pharmacokinetics (PK) and
immunogenicity of adalimumab following subcutaneous (SC) injection in this HS
surgical population will also be assessed.

The purpose of the photos and digital imaging sub-study is to determine whether
the use of digital imaging proves to be a more efficient and precise
measurement of skin wound healing compared to tracing on acetate paper.

This is a Phase 4, Interventional, Double-Blind, Randomised,
Placebo-Controlled, Multicenter study.

Subjects receive subcutaneous injections of adalimumab for the duration of 23
weeks in addition to the standard of care for HS. In this case, patients
undergo surgery (excision of HS site) as part of their standard of care. Where
needed additional examinations are applicable, e.g. physicial examination,
blood draws and questionnnaires. When subjects have given approval for imaging,
photographs will be taken of their HS lesions.

For patients who are participating in the optional exploratory (extra) study:
extra blood draws (total 164,5 ml; fasting), 5 skin-swabs, obtaining
skin-biopsies (total of 6) and maintaining and analysis of leftover surgical
tissue. The patient can choose which materials are collected for this optional
study.

Adalimumab therapy has a well-established and well described safety profile
based on extensive post-marketing experience and continued clinical trial
patient exposure since the first approved indication in 2002 for rheumatoid
arthritis. The safety and efficacy of adalimumab in HS has been explored in the
Phase 2 trial and in two Phase 3 trials. To date, 733 subjects with HS have
been studied in adalimumab clinical studies in the HS clinical program, for a
total of 836.3 patient-years of adalimumab exposure. Treatment-emergent adverse
events (TEAEs) were reported in 595 subjects (81.2%) for a rate of 417.6
events/100 patient-years. Worsening hidradenitis, nasopharyngitis, headache,
and upper respiratory tract infection were the most frequently reported TEAEs.

Efficacy data from the adalimumab HS clinical program demonstrate that the
recommended adalimumab dosing regimen is an effective treatment for
inflammatory lesions and skin pain of HS among moderate to severe HS subjects
who had an inadequate response or were intolerant to oral antibiotic therapy.

Subjects enrolled in this study will be eligible patients who will have
surgical intervention as part of their routine care. Standard practices
regarding perioperative and operative care will be under the direction of the
dermatologist and/or surgeon and will not be directed per this protocol. It is
expected the routine risks of surgery will be essentially unchanged by
participation in this study. The subject will be closely followed for any
adverse events and the relationship to study drug as assessed by the Study
Investigator will be recorded and analysed. As described above for active HS
lesions, there is the possibility that adalimumab may positively affect the
active HS lesions in the planned surgical site, which might then allow for a
less extensive surgical intervention. Adalimumab is predicted to have neither a
positive or negative impact on fibrotic lesions within the HS surgical site.