Inclusion Criteria:
* Male or Female at least 18 years of age, and provide informed consent prior to study procedures.
* Have moderate to severe HS classified as Hurley stage II or III for at least 6 months refractory to conventional therapies with a total AN count of greater than or equal to 5 prior to enrollment/randomization
* Failed at least 1 course of oral antibiotics for treatment of HS (or demonstrated intolerance to, or had a contraindication to oral antibiotics for treatment of their HS).
* Women of Childbearing potential must have a urine pregnancy test at screening, wk 0 and prior to administration of the study medication
* Women of childbearing potential must be willing to continue a highly effective method of birth control throughout the study (oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository (if available in their locale); male partner sterilization (the vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the preferred and usual lifestyle of the participant).
* Negative screening for tuberculosis (TB) (Quantiferon Gold, T-spot) within 3 months prior to screening
* If a positive history of latent tuberculosis:
* Currently receiving treatment for latent TB per standard of care
* Have documentation of having completed treatment within 5 years prior to baseline
* Agree not to have a live vaccination during the study.
Exclusion Criteria:
* Any other active skin disease that in the opinion of the investigator would interfere with the assessment of HS
* Have greater than 20 draining fistulas at screening or Day 1 prior to enrollment/randomization
* Receipt of non-biologic treatments for HS within 4 weeks prior to baseline other than antibiotics or hormonal therapy
* Receipt of biologic agents within 3 months prior to baseline
* Receipt of any other investigational product within 3 months prior to baseline
* Receipt of new oral antibiotics or hormonal therapy within 6 weeks prior to baseline.
* Subjects may be included if they are on steady dose of doxycycline or tetracycline antibiotics only for at least 6 weeks prior to baseline visit and may not change or discontinue dose during course of study.
* Receipt of intralesional kenalog injections within 2 weeks prior to baseline
* Any uncontrolled diagnosis or condition that in the opinion of the investigator will interfere with the assessments or the study.
* Currently has a malignancy or a history of a malignancy within 5 years before screen (except successfully treated non-melanoma skin cancer or cervical carcinoma in situ)
* History of an ongoing, chronic or recurrent infectious disease
* Are currently pregnant, breastfeeding, or planning to get pregnant during the study.
* Previous hypersensitivity reaction to siplizumab or to any of the components
* Known infection with HIV, hepatitis B or hepatitis C at screening or randomization.
Patients who are Hepatitis B Core antibody and/or Hep B Surface Antigen positive will be excluded from this study. Patients who are Hepatitis C ab positive will also be excluded from this study.
* Underlying condition (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 subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
* Any of the following laboratory abnormalities within 30 days of enrollment:
* White blood count (WBC) \< 3 x 103/μL;,
* CD4+ count below the lower limit of normal,
* Platelet count \< 150,000 /μL,
* Hemoglobin \< 10 g/dL,
* ALT ≥ 2x upper limit of normal (ULN) or
* AST ≥ 2x ULN
* Serum creatinine \>1.5x ULN in adults.
* Positive molecular testing of SARS-CoV-2
* ALC less than 800 lymphocytes/mm3
