A Multinational, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Investigate the Use of Benralizumab as a Treatment Option for Patients With Bullous Pemphigoid.

JRCT ID: jRCT2071210014

Registered date:26/04/2021

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: Bullous Pemphigoid
• Date of first enrollment: 26/03/2021
• Target sample size: 12
• Countries of recruitment: United States,Japan,Australia,Japan,Bulgaria,Japan,France,Japan,Germany,Japan,Israel,Japan,Italy,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

This study is designed to assess the efficacy and safety of a benralizumab 60 mg loading dose followed by repeat dosing of subcutaneously (SC) administered benralizumab 30 mg versus placebo in adult participants with symptomatic BP.

Following screening, about 120 eligible participants will be randomized 1:1 to receive either benralizumab or placebo.

Double-blind treatment period (0w-36w): In the benralizumab group, 60 mg initially and 30 mg thereafter are subcutaneously administered every 4 weeks. In the placebo group, placebo is subcutaneously administered every 4 weeks.

Open-label extension period (36w-): All participants who complete the double-blind dosing period will be given the option of receiving benralizumab 30 mg subcutaneously every 4 weeks.

Outcome(s)

Primary Outcome

Proportion of participants who are in complete remission while off OCS for 2 months or more at Week 36 (FAS) [ Time Frame: Week 36 ]

A binary response, whereby a responder is defined as a participant who is in complete remission while off OCS for 2 months or more at Week 36. Otherwise, a participant is a non-responder.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Informed Consent/Age
1.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol.

2.Adult participants 18 years of age or more at the time of signing the ICF.

Type of Participant and Disease Characteristics

3.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).

4.BPDAI activity score 24 or more at the screening and randomization visits.

5.Candidate for systemic corticosteroid therapy.
Sex 6 Male or female.

Reproduction 7 Female participants capable of having children must meet both of the following conditions ([a] and [b]):

(a) Have a negative urine pregnancy test prior to administration of the IP 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 woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of the surgical success.

(c) 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 or more to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply: (i) Women < 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 woman of childbearing potential.

(ii) Women 50 years old or more will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions
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. 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.

6. 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.

7. 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.

8. 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 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.

b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level 3 times or more 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.

9. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.

Prior/Concomitant Therapy
10. 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.

Other Exclusions
11. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.

12. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.

13. Known history of allergy or reaction to any component of the IP formulation.

14. Receipt of live attenuated vaccines 30 days prior to the date of randomization.

15. Previously received benralizumab (MEDI-563, FASENRA).

16. 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.

17. Planned major surgical procedures during the conduct of the study.

18. Previous randomization in the present study.

19. Concurrent enrollment in another clinical trial.

20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

21. For women only: Currently pregnant, breastfeeding, or lactating women. (a) A urine pregnancy test must be performed for women of childbearing potential (WOCBP) at Visit 1 and each subsequent treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the participant should be excluded.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT04612790