A Study to Investigate the Use of Benralizumab in Patients With Bullous Pemphigoid.

NCT04612790 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: D325AC000022023-505033-27-002020-000287-32
• Study Type: interventional
• Target: 67
• Locations: 11 countries
• Sites: 39

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).

Conditions

Bullous Pemphigoid

Keywords

Bullous pemphigoid; rare disease; skin eruptions; itching autoimmune blistering disorder; eosinophilia; urticarial or eczematous or erythematous plaques; bullae; pruritus

Outcome Measures

Primary Outcomes (1)

• Percentage of Responders at Week 36

  A responder was defined as a participant who was in complete remission while off OCS for ≥2 months at Week 36.

  At Week 36

Secondary Outcomes (5)

• Percentage of Participants Who Remained Relapse-Free up to Week 36

  Up to Week 36

• Cumulative OCS Exposure From Baseline to Week 36

  Baseline (Day 1) and Week 36

• Change From Baseline in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score at Week 36

  Baseline (Day 1) and Week 36

• Change From Baseline in BPDAI-Pruritus Score at Week 36

  Baseline (Day 1) and Week 36

• Cumulative OCS Exposure From Baseline to Week 16

  Baseline (Day 1) and Week 16

Study Arms (2)

Benralizumab

EXPERIMENTAL

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.

Biological: Benralizumab

Placebo

EXPERIMENTAL

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.

Biological: Placebo

Interventions

Benralizumab BIOLOGICAL

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.

Also known as: Benralizumab, Benra, Fasenra

Benralizumab

Placebo BIOLOGICAL

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Informed Consent/Age
• 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.
• Adult participants ≥ 18 years of age at the time of signing the ICF.
• Type of Participant and Disease Characteristics
• 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).
• 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).
• 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.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions
• 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.
• 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 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.
• 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 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.
• 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.
• A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (39)

Research Site

Phoenix, Arizona, 85006, United States

Location

Research Site

Scottsdale, Arizona, 85260, United States

Location

Research Site

Centennial, Colorado, 80112, United States

Location

Research Site

Margate, Florida, 33063, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Beverly, Massachusetts, 01915, United States

Location

Research Site

Kogarah, 2217, Australia

Location

Research Site

Parkville, 3050, Australia

Location

Research Site

Westmead, 2145, Australia

Location

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Haskovo, 6300, Bulgaria

Location

Research Site

Sofia, 1431, Bulgaria

Location

Research Site

Beijing, 100730, China

Location

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Guangzhou, 510515, China

Location

Research Site

Hohhot, 10050, China

Location

Research Site

Shanghai, 200025, China

Location

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Lille, 59037, France

Location

Research Site

Marseille, 13008, France

Location

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Nice, 06200, France

Location

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Rouen, 76031, France

Location

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Bad Bentheim, 48455, Germany

Location

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Bielefeld, 33647, Germany

Location

Research Site

Dresden, 01307, Germany

Location

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Leipzig, 04103, Germany

Location

Research Site

Thessaloniki, 56249, Greece

Location

Research Site

Ramat Gan, 5262000, Israel

Location

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Tel Aviv, 64239, Israel

Location

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Catania, 95123, Italy

Location

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Florence, 50121, Italy

Location

Research Site

Rome, 168, Italy

Location

Research Site

Iruma-Gun, 350-0495, Japan

Location

Research Site

Kitakyusyu-shi, 806-8501, Japan

Location

Research Site

Kurume-shi, 830-0011, Japan

Location

Research Site

Okayama, 700-8558, Japan

Location

Research Site

Ōta-ku, 143-8541, Japan

Location

Research Site

Sapporo, 060-8648, Japan

Location

Research Site

Urayasu-shi, 279-0021, Japan

Location

Research Site

Alicante, 03010, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Related Links

• FJORD Brochure
• FJORD Flyer
• A website on the FJORD study.
• CSR Synopsis

MeSH Terms

Conditions

Pemphigoid, Bullous; Rare Diseases; Eosinophilia; Urticaria; Blister; Pruritus

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Hypersensitivity, Immediate; Hypersensitivity; Pathological Conditions, Anatomical; Skin Manifestations; Signs and Symptoms

Limitations and Caveats

The study was terminated following a pre-planned futility analysis as the efficacy results did not pass the pre-defined futility hurdle with no new safety concerns.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: November 3, 2020
• Study Start: March 31, 2021
• Primary Completion: October 26, 2023
• Study Completion: October 26, 2023
• Last Updated: November 29, 2024
• Results First Posted: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

JP (7); GR (1); ES (3); US (6); DE (4); BU (2); FR (4); AU (3); IT (3); CN (4); IL (2)