A Study to Investigate the Use of Benralizumab in Patients With Bullous Pemphigoid.
- Conditions
- Bullous Pemphigoid
- Interventions
- Biological: Placebo
- Registration Number
- NCT04612790
- Lead Sponsor
- AstraZeneca
- Brief Summary
The purpose of this study is to investigate the use of benralizumab is effective in the treatment of patients symptomatic Bullous Pemphigoid (BP).
- Detailed Description
Bullous pemphigoid (BP) is a rare disease mainly affecting the elderly. BP is associated with significant morbidity and increased mortality secondary to increased risk of secondary infections, comorbid conditions, and serious side effects from high-dose steroids and immunosuppressants. The aim of this study is to investigate the use of benralizumab as a treatment for patients symptomatic with Bullous Pemphigoid (BP).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 67
Participants are eligible to be included in the study only if all of the following criteria apply:
Informed Consent/Age
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Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
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Adult participants ≥ 18 years of age at the time of signing the ICF.
Type of Participant and Disease Characteristics
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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:
- Histology.
- 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):
(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).
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BPDAI activity score ≥ 24 at the screening and randomization visits.
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Candidate for systemic corticosteroid therapy.
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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).
Sex 7 Male or female.
Reproduction 8 Female participants capable of having children must meet both of the following conditions ([a] and [b]):
(a) 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.
(ii) Progestogen-only hormonal contraception associated with inhibition of ovulation - oral, injectable, or implantable.
(iii) Intrauterine device. (iv) Intrauterine hormone-releasing system. (v) Bilateral tubal occlusion. (vi) Sexual abstinence, ie, 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).
(vii) Vasectomized sexual partner provided that partner is the sole sexual partner of the female of childbearing potential (FOCBP) study participant and that the vasectomized partner has received medical assessment of the surgical success.
(c) Females not of childbearing potential are defined as females who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Females 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: (i) Females < 50 years old will be considered 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 female of childbearing potential.
(ii) Females ≥ 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
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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, and drug-induced BP.
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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).
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Current or history of malignancy within 5 years before the screening visit with the following exceptions:
- Participants treated for in situ carcinoma of the cervix who have completed curative therapy and are in remission for at least 12 months prior to signing the informed consent and
- 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.
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History of anaphylaxis to any biologic therapy or vaccine.
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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.
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Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), hematology, or clinical chemistry 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.
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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 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 participant does not have an active liver disease and meets other eligibility criteria.
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A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
Prior/Concomitant Therapy
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Use of immunosuppressive medication, including, but not limited to: methotrexate, cyclosporine, azathioprine, within 4 weeks or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
Other Exclusions
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Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
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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 (eg, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases) can participate in the study.
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Known history of allergy or reaction to any component of the IP formulation.
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Receipt of live attenuated vaccines 30 days prior to the date of randomization.
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Previously received benralizumab (MEDI-563, FASENRA).
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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.
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Planned elective major surgical procedures during the conduct of the study.
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Previous randomization in the present study.
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Concurrent enrollment in another interventional (eg, investigational drug or device) clinical trial.
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Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
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For females only: Currently pregnant, breastfeeding, or lactating females.
(a) A urine pregnancy test must be performed for FOCBP 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.
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Participant is unable to complete PRO assessments because of cognitive function (eg, dementia).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Benralizumab Benralizumab Benralizumab subcutaneously (SC) loading dose followed by repeat dosing of SC benralizumab plus Oral Corticosteroids per SoC tapering. Open-Label (OLE): after completion of the double-blind treatment period, all participants will have the option of entering an OLE period, starting at week 36 benralizumab SC until study closure. Placebo Placebo Placebo plus Oral Corticosteroids per SoC tapering. Open-Label (OLE): after completion of the double-blind treatment period, all participants will have the option of entering an OLE period, starting at week 36 benralizumab SC until study closure.
- Primary Outcome Measures
Name Time Method Percentage of Responders at Week 36 At Week 36 A responder was defined as a participant who was in complete remission while off OCS for ≥2 months at Week 36.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Remained Relapse-Free up to Week 36 Up to Week 36 Relapse was defined as the appearance of 3 or more new lesions per month (blisters, eczematous lesions, or urticarial plaques); or at least 1 large (\>10 centimeter \[cm\] diameter) eczematous lesion or urticarial plaques that did not heal within 1 week; or the extension of established lesions or daily pruritus in participants who had achieved disease control.
Cumulative OCS Exposure From Baseline to Week 36 Baseline (Day 1) and Week 36 The cumulative OCS exposure was estimated as the sum over the relevant 4-week periods from the mixed-effect model for repeated measures (MMRM) model. Baseline was defined as the last recorded value on or prior to the date of randomization. Equivalents were prednisone equivalents (converted from mg).
Change From Baseline in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score at Week 36 Baseline (Day 1) and Week 36 BPDAI is a clinician completed tool that is used for independent disease severity assessment to measure disease extent in BP. The total BPDAI activity score is calculated as the arithmetic sum of the 3 subcomponents - cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. The BPDAI total activity gives an indication of disease activity, with score range from 0 (no disease activity) to 360 (severe disease activity). Higher scores indicating greater disease activity. Baseline was defined as the last recorded value on or prior to the date of randomization.
Change From Baseline in BPDAI-Pruritus Score at Week 36 Baseline (Day 1) and Week 36 The BPDAI-Pruritus is a separate component of the BPDAI that asks the participant to grade the severity of pruritus over the past 24 hours, the past week, and the past month. For each recall period, severity of pruritus is rated on a numeric rating scale (NRS) ranging from 0 for no itch to 10 for maximal itching. The BPDAI-Pruritus score was computed as the sum of 3 components ranging from 0 to 30. Higher scores indicated worse condition. Baseline was defined as the last recorded value on or prior to the date of randomization.
Cumulative OCS Exposure From Baseline to Week 16 Baseline (Day 1) and Week 16 The cumulative OCS exposure was estimated as the sum over the relevant 4-week periods from the MMRM model. Baseline was defined as the last recorded value on or prior to the date of randomization. Equivalents were prednisone equivalents (converted from mg).
Trial Locations
- Locations (1)
Research Site
🇪🇸Madrid, Spain