A study to investigate the use of benralizumab in patients with bullous pemphigoid

Phase 1

Conditions: Bullous Pemphigoid
MedDRA version: 21.1Level: LLTClassification code 10006567Term: Bullous pemphigoidSystem Organ Class: 100000004858
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2020-000287-32-FR

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 120

Inclusion Criteria

1. Adult participants = 18 years of age
2. 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:
(a) Histology.
(b) Positive direct immunofluorescence (from skin biopsy) (IgG and/or C3 at the
basement membrane zone).
(c) AND at least one of the following serologic assessments positive (all assessed from
participant’s blood sample):
(i) indirect immunofluorescence (IgG on the roof of salt- split skin).
(ii) positive serology on ELISA for BPAG1 (230-kd).
(iii) positive serology on ELISA for BPAG2 (180-kd).
3. BPDAI activity score = 24 at the screening and randomization visits.
4. Candidate for systemic corticosteroid therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 108

Exclusion Criteria

1. Forms of BP other than classic, predominantly cutaneous BP: eg, mucous membrane BP, epidermolysis bullosa acquisita, Brunsting-Perry BP, p200 BP, p105 BP, BP with concomitant pemphigus vulgaris, drug-induced BP (eg, new onset or current exacerbation from angiotensin-converting enzyme inhibitors, penicillamine, furosemide, phenacetin, dipeptidyl peptidase-4 inhibitors or some immuno-Oncology therapies).
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
(a) Affect the safety of the participant throughout the study.
(b) Influence the findings of the studies or their interpretations.
(c) Prevent the participant’s ability to complete the entire duration of study.
(d) Impact the participant’s ability to complete the required PRO assessments.
3. Current malignancy, or history of malignancy, except for:
(a) Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained.
(b) 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, and assent when applicable, was obtained.
4. History of anaphylaxis to any biologic therapy or vaccine.
5. History of Guillain-Barré syndrome.
6. 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.
7. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening, which in the 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, or the participant’s ability to complete entire duration of the study.
8. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the participant at risk or interfere with study assessments.
9. Current active liver disease.
(a) 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 subject 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.
(b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level =3 times the 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 subject does not have an active liver disease and meets other eligibility criteria.
10. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the clinical efficacy of benralizumab with placebo in participants with symptomatic BP;Secondary Objective: 1. To compare the effect of benralizumab with placebo on supportive measures of clinical efficacy in participants with symptomatic BP up to Week 36.<br>2. To compare the effect of benralizumab with placebo on clinical efficacy in participants with symptomatic BP up to Week 16.<br>3. To estimate the PK and immunogenicity of benralizumab in participants with BP.;Primary end point(s): A binary response, whereby a responder is defined as a participant who is in partial or complete<br>remission while off OCS for = 2 months at Week 36.;Timepoint(s) of evaluation of this end point: at Week 36

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key secondary : <br>• Proportion of participants who remain relapse-free up to Week 36.<br>• Cumulative OCS exposure (mg/kg) from baseline to Week 36.<br>• Change from baseline in BPDAI activity score at Week 36.<br>• Change from baseline in BPDAI-Pruritus at Week 36.<br>• Cumulative OCS exposure (mg/kg) from baseline to Week 16.;Timepoint(s) of evaluation of this end point: various time points as per protocol

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