Inclusion Criteria:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol.
• Adult participants ≥ 18 years of age at the time of signing the ICF.
• Participants must have clinical features of BP (eg, urticarial or eczematous or erythematous plaques, bullae, pruritus) at the screening visit and confirmed diagnosis with histology, direct immunofluorescence, and serology at randomization. Required for inclusion:
• Positive direct immunofluorescence (from skin biopsy) (IgG and/or C3 at the basement membrane zone) AND at least one of the following serologic assessments positive (all assessed from participant's blood sample):
  • indirect immunofluorescence (IgG on the roof of salt- split skin);
  • positive serology on ELISA for BPAG1 (230-kd);
  • positive serology on ELISA for BPAG2 (180-kd).
• BPDAI activity score ≥ 24 at the screening and randomization visits.
• Candidate for systemic corticosteroid therapy.
• Able to complete PRO assessments on a tablet and on a handheld device. Some participants may be exempted from completing home PROs on the handheld device upon agreement with the AstraZeneca physician (eg, if the patient has a medical condition such as BP lesions of the fingers/hand, a neurologic condition affecting fingers/hand or severe visual impairment).
• Male or female.
• Female participants capable of having children must meet both of the following conditions ([a] and [b]):
  • Have a negative urine pregnancy test at screening and (b) Must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and within 12 weeks after last dose of IP. Highly effective forms (those that can achieve a failure rate of less than 1% per year when used consistently and correctly) of birth control include: (i) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - oral, intravaginal, or transdermal;
  • Progestogen-only hormonal contraception associated with inhibition of ovulation - oral, injectable, or implantable;
  • Intrauterine device.;
  • Intrauterine hormone-releasing system;
  • Bilateral tubal occlusion;
  • Sexual abstinence; i.e., refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant);
  • Vasectomized sexual partner provided that partner is the sole sexual partner of the woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of the surgical success.
• Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for ≥ 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:
  • Women < 50 years old will beconsidered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone (FSH) levels in the postmenopausal range. Until FSH is documented to be within menopausal range, treat the participant as a woman of childbearing potential;
  • Women ≥ 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:

• Forms of BP other than classic, predominantly cutaneous BP; e.g., mucous membrane BP, epidermolysis bullosa acquisita, Brunsting-Perry BP, p200 BP, p105 BP, BP with concomitant pemphigus vulgaris, and drug-induced BP.
• Comorbid disease that in the Investigator's judgement might interfere with the evaluation of the IP or safety of the participant. This includes any disorder that in the opinion of the Investigator is not stable (eg, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment).
• Current history of malignancy within 5 years before the screening visit with the following exceptions:
  • Participants treated for in situ carcinoma who have completed curative therapy was completed of the cervix and are in remission for at least 12 months prior to signing the informed consent;
  • Participants with superficial basal cell or squamous skin cancer;
  • Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• History of anaphylaxis to any biologic therapy or vaccine.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
• Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), hematology, or clinical chemistry during screening, which inthe opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study;
• Current active liver disease:
  • Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis;
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 timesthe upper limit of normal, confirmed by repeated testing during screening period.  Transient increase of AST/ALT level that resolves by the time of randomization is acceptable if in the Investigator's opinion the participant does not have an active liver disease and meets other eligibility criteria.
• A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
• Use of immunosuppressive medication (including but not limited to: methotrexate, cyclosporine, azathioprine, intramuscular (IM) long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
• Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer. Participants on stable therapy for at least 3 months before randomization who intend to stay on treatment throughout the study with marketed biologics that are not likely to interfere with the assessment of safety and/or efficacy of benralizumab (e.g., for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases) can participate in the study.
• Known history of allergy or reaction to any component of the IP formulation.
• Receipt of live attenuated vaccines 30 days prior to the date of randomization.
• Previously received benralizumab (MEDI-563, FASENRA).
• Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent and anticipated changes in immunotherapy throughout the study.
• Planned major surgical procedures during the conduct of the study.
• Previous randomization in the present study.
• 18. Concurrent enrollment in another interventional (eg, investigational drug or device) clinical trial.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• For women only: Currently pregnant, breastfeeding, or lactating women:
  • A urine pregnancy test must be performed for women of childbearing potential (WOCBP) at Visit 1. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the participant should be excluded.
• Participant is unable to complete PRO assessments because of cognitive function (e.g., dementia).

Eligibility last updated 2/15/23. Questions regarding updates should be directed to the study team contact.