A Phase 2 Multicenter, Investigator-blind, Subject-blind, Placebo-controlled Study of the Efficacy, Safety, and Pharmacokinetics of Bimekizumab in Subjects with Moderate to Severe Hidradenitis Suppurativa

To be eligible to participate in this study, all of the following criteria must be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent Form (ICF) is signed and dated by the subject or by the legal representative.
2. Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the Investigator.
3. Adult subjects (18 to 70 years of age, inclusive) must have a diagnosis of HS for at least 1 year prior to Baseline.
4. Hidradenitis suppurativa lesions must be present in at least 2 distinct anatomic areas, 1 of which must be at least Hurley Stage II or Hurley Stage III.
5. Subject must have stable HS for at least 2 months prior to Screening and also at the Baseline Visit as assessed by the Investigator through subject interview and review of medical history.
6. Subject must have had an inadequate response to at least a 3-month study of an oral antibiotic for treatment of HS (or exhibited recurrence after discontinuation to, or demonstrated intolerance to, or have a contraindication to oral antibiotics for treatment of their HS) as assessed by the Investigator through subject interview and review of medical history.
7. Subject must have a total abscess and inflammatory nodule count *3 at the Baseline Visit.
8. Subject must be considered, in the opinion of the Investigator, to be a suitable candidate for treatment with adalimumab per regional labeling.
9. Subject must have a C-reactive protein (CRP) level >3mg/L at the Baseline Visit.
10. Subject has a negative tuberculosis (TB) Screening assessment (including an interferon gamma release assay [IGRA] test using QuantiFERON-TB Gold test, or equivalent) and negative posterior-anterior chest x-ray (CXR) or Computed Axial Tomography (CAT) scan of chest at Screening or within 3 months prior to Screening (nuclear magnetic resonance films are not acceptable).
11. Subject must agree to daily use (and throughout the entirety of the study) of 1 of the following over-the-counter topical antiseptics on their HS lesions: chlorhexidine gluconate, triclosan, benzoyl peroxide, or dilute bleach in bathwater.
12. Subject is assessed to have no other medical condition that would preclude their participation in the study, as determined by the Principal Investigator based upon the results of a medical history, physical examination, laboratory profile, and a 12-lead ECG performed during the Screening Period, and confirmed at Baseline.
13. Female subjects must be postmenopausal (at least 1 year; to be confirmed hormonally as part of the Screening process, if less than 2 years since last menstrual period), permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of IMP, and have a negative pregnancy test at Visit 1 (Screening) and immediately prior to first dose. The following methods are considered highly effective when used consistently and correctly.
-combined (estrogen and progestogen) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal).
-progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
-intrauterine device (IUD).
-ntrauterine hormone-releasing system (IUS).
-bilateral tubal occlusion.
-vasectomized partner (where postvasectomy testing had demonstrated sperm clearance).
-sexual abstinence if it is in accordance with a subject*s preferred and common lifestyle. Subjects who use abstinence as a form of birth control must agree to abstain from heterosexual intercourse until 20 weeks after the last dose of IMP. Study personnel must confirm the continued use of abstinence is still in accordance with the subject*s lifestyle at regular intervals during the study.;Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of IMP (anticipated 5 half-lives).

Subjects are not permitted to enroll in the study if any of the following criteria is met:
1. Prior treatment with anti IL17s or participation in an anti-IL17 study.
2. Subjects who previously received anti-TNFs.
3. Subjects participating in another study of a medication or a medical device under investigation within the last 3 months or at least 5 half-lives of the investigational product, whichever is greater, or is currently participating in another study of a medication or medical device under investigation.
4. Subject has a known hypersensitivity to any excipient(s) of bimekizumab or adalimumab.
5. Subject is using concomitant oral analgesics for HS-related or non-HS-related pain at study entry:
-Opioid analgesics within 14 days prior to the Baseline Visit.
-Non-opioid oral analgesics unless at a stable dose for at least 14 days prior to the Baseline Visit (PRN use is not considered a stable dose).
6. Subject requires, or is expected to require, opioid analgesics for any reason (excluding tramadol).
7. Subject received prescription topical therapies for the treatment of HS within 14 days prior to the Baseline Visit.
8. Subject received systemic non-biologic therapies for HS with potential therapeutic impact for HS less than 28 days prior to Baseline Visit.
9. Subject has a draining fistula count >20 at the Baseline Visit.
10. Subjects with a diagnosis of inflammatory conditions other than HS, including but not limited to PSO, PsA, RA, sarcoidosis, or systemic lupus erythematosus. Subjects with a diagnosis of CD or ulcerative colitis are allowed as long as they have no active symptomatic disease at Screening or Baseline.
11. Subjects with a history of chronic or recurrent infections, or a serious or life-threatening infection within the 6 months prior to the Baseline Visit (including herpes zoster). Subjects with a high risk of infection in the Investigator*s opinion (eg, subjects with leg ulcers, indwelling urinary catheter, persistent or recurrent chest infections, prior prosthetic joint infection at any time, subjects who are permanently bedridden or wheelchair assisted).
12. Subject has any current sign or symptom that may indicate an active infection (except for common cold), or has had an infection requiring systemic antibiotics within 2 weeks of the Baseline Visit.
13. Any other active skin disease or condition (eg, bacterial, fungal or viral infection) that may interfere with assessment of HS.
14. Subject has history of or current clinically active infection with Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB), Blastomyces, or Aspergillus or current active Candidiasis (local or systemic).
15. Subject has acute or chronic viral hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Subjects who have evidence of, or tested positive for, hepatitis B or hepatitis C are excluded.
-A positive test for the HBV is defined as: 1) positive for hepatitis B surface antigen; or, 2) positive for anti-hepatitis B core antibody.
-A positive test for the HCV is defined as: 1) positive for hepatitis C antibody, and 2) positive via a confirmatory test for HCV (for example, HCV polymerase chain reaction).
16. Subjects with known TB infection, at high risk of acquiring TB infection, with latent TB infection (LTB), or current or history of NTMB infection (refer to Section 11.3.1 for details on determining full TB exclusion criteria).
17. Subject has a primary immunosuppressive condition, including taking immunosuppressive therapy following an organ transplant, or has had a splenectomy.
18. Subjects with concurrent malignancy or history of malignancy (including surgically resected uterine/cervical carcinoma-in-situ) during the past 5 years will be excluded, with the following exceptions that may be included:
a. *3 excised or ablated, basal cell carcinomas of the skin.
b. One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening.
c. Actinic keratosis(-es).
d. Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening).
19. Subject has a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
20. Subject has history of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.
21. Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac (eg, congestive heart failure, New York Heart Association Grade 3 and 4), gastrointestinal (note: subjects with active peptic ulcer disease are excluded; subjects with a history of peptic ulcer disease are allowed), neurological disease, or inflammatory bowel disease.
22. Subject has a history of uncompensated heart failure, fluid overload, or myocardial infarction, or evidence of new onset ischemic heart disease or (in the opinion of the Investigator) other serious cardiac disease, within 12 weeks prior to the Baseline Visit.
23. Presence of active suicidal ideation, or positive suicide behavior using the *Baseline* version of the Columbia-Suicide Severity Rating Scale (C-SSRS) and the HADS with either of the following criteria:
-Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (*Yes*) to either question 4 or question 5 of the *Screening/Baseline* version of the C-SSRS at Screening.
-HADS-D score *10 and HADS-A score *15.
24. Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), *alkaline phosphatase (ALP), or >ULN total bilirubin (*1.5xULN total bilirubin if known Gilbert*s syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert*s syndrome (ie, direct bilirubin <35%).
*An isolated elevation between 2xULN and <3xULN of ALP is acceptable in the absence of an identified exclusionary medical condition.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation during the Screening Period. Upon retesting, subjects whose ALT, AST, or ALP remain above the thresholds defined above, should not be randomized.
For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF).
If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at Screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor and/or UCB Study Physician.
25. Subjects with clinically significant laboratory abnormalities (eg, creatinine >1.5xULN, neutropenia <1.5x109/L, hemoglobin <8.5g/dL, lymphocytes <1.0x109/L, platelets <100x109/L). Individual Screening tests for which the results are in error, borderline, or indeterminate for inclusion in the study, can be repeated once for confirmation during the Screening Period if they are within 25% of the exclusion limit. Upon retesting, subjects whose results remain outside this threshold should not be randomized.
26. Subject has 12-lead ECG with changes considered to be clinically significant upon medical review (eg, QTc using Fridericia*s correction [QTcF] >450ms, bundle branch block, evidence of myocardial ischemia).
27. Subject has received any live (includes attenuated) vaccination within the 8 weeks prior to the Baseline Visit (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal influenza vaccination is not permitted). Live vaccines are not allowed during the study or for 20 weeks after the last dose of IMP.
28. Subject has received Bacillus Calmette-Guerin vaccination within 1 year prior to IMP administration.
29. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
30. Subjects with any other condition which, in the Investigator's judgement, would make the subject unsuitable for inclusion in the study.
31. Subject has previous exposure to adalimumab.
32. Subjects are Investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
33. Subjects are UCB employees or are employees of third-party organizations involved in the study.