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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04612790




Registration number
NCT04612790
Ethics application status
Date submitted
12/10/2020
Date registered
3/11/2020

Titles & IDs
Public title
A Study to Investigate the Use of Benralizumab in Patients With Bullous Pemphigoid.
Scientific title
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 (FJORD)
Secondary ID [1] 0 0
2023-505033-27-00
Secondary ID [2] 0 0
D325AC00002
Universal Trial Number (UTN)
Trial acronym
FJORD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bullous Pemphigoid 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Benralizumab
Treatment: Other - Placebo

Experimental: 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.

Experimental: 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.


Treatment: Other: 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.

Treatment: Other: 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.

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of participants who are in complete remission while off OCS for = 2 months at Week 36 (FAS)
Timepoint [1] 0 0
Week 36
Secondary outcome [1] 0 0
Proportion of participants who remain relapse-free up to Week 36.
Timepoint [1] 0 0
Week 36
Secondary outcome [2] 0 0
Cumulative OCS exposure (mg/kg) from baseline to Week 36.
Timepoint [2] 0 0
Week 36
Secondary outcome [3] 0 0
Change from baseline in BPDAI activity score at Week 36.
Timepoint [3] 0 0
Week 36
Secondary outcome [4] 0 0
Change from baseline in BPDAI-Pruritus score at Week 36.
Timepoint [4] 0 0
Week 36
Secondary outcome [5] 0 0
Proportion of participants in sustained complete/ partial remission on minimal OCS/ off OCS for at least 2 months at week 36
Timepoint [5] 0 0
Week 36
Secondary outcome [6] 0 0
Cumulative time (weeks) in complete remission off OCS from baseline to Week 36
Timepoint [6] 0 0
Week 36
Secondary outcome [7] 0 0
Proportion of participants off OCS by Week 36.
Timepoint [7] 0 0
Week 36
Secondary outcome [8] 0 0
IGA Score at Week 36.
Timepoint [8] 0 0
Week 36
Secondary outcome [9] 0 0
Change from baseline in IGA score at Week 36.
Timepoint [9] 0 0
Week 36
Secondary outcome [10] 0 0
Cumulative OCS exposure (mg/kg) from baseline to Week 16.
Timepoint [10] 0 0
Week 16
Secondary outcome [11] 0 0
Proportion of participants who remain relapse-free up to Week 16.
Timepoint [11] 0 0
Week 16
Secondary outcome [12] 0 0
Proportion of participants with any clinical benefit (eg, partial and complete remission during taper, with no steroid use, or with minimal steroid use [ie, < 0.1 mg/kg/day]) at Week 16.
Timepoint [12] 0 0
Week 16
Secondary outcome [13] 0 0
Time to disease control, OCS dose (mg/kg) at disease control and time to the end of the consolidation phase.
Timepoint [13] 0 0
Week 16
Secondary outcome [14] 0 0
Change from baseline in BPDAI activity score at Week 16.
Timepoint [14] 0 0
Week 16
Secondary outcome [15] 0 0
Change from baseline in BPDAI-Pruritus score at Week 16.
Timepoint [15] 0 0
Week 16
Secondary outcome [16] 0 0
Serum benralizumab concentration.
Timepoint [16] 0 0
Weeks 0,2,4,6,8,16,24,36, 60 and 12 weeks after last IP dose
Secondary outcome [17] 0 0
Determination of Anti-drug antibodies (ADA) in serum
Timepoint [17] 0 0
Weeks 0,4,6,8,16,24,36, 60 and 12 weeks after last IP dose

Eligibility
Key inclusion 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 as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Adult participants = 18 years of age 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:

1. Histology.
2. Positive direct immunofluorescence (from skin biopsy) (IgG and/or C3 at the basement membrane zone).
3. 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 at the screening and randomization visits.
5. Candidate for systemic corticosteroid therapy.
6. 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.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion 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, and drug-induced BP.
2. 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).
3. Current or history of malignancy within 5 years before the screening visit with the following exceptions:

1. 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
2. Participants with superficial basal cell or squamous skin cancer.
3. 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.
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, 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.
7. Current active liver disease.

1. 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.
2. 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.
8. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.

Prior/Concomitant Therapy
9. 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
10. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
11. 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.
12. Known history of allergy or reaction to any component of the IP formulation.
13. Receipt of live attenuated vaccines 30 days prior to the date of randomization.
14. Previously received benralizumab (MEDI-563, FASENRA).
15. 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.
16. Planned elective major surgical procedures during the conduct of the study.
17. Previous randomization in the present study.
18. Concurrent enrollment in another interventional (eg, investigational drug or device) clinical trial.
19. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
20. 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.
21. Participant is unable to complete PRO assessments because of cognitive function (eg, dementia).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Kogarah
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment hospital [3] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Haskovo
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Sofia
Country [8] 0 0
China
State/province [8] 0 0
Beijing
Country [9] 0 0
China
State/province [9] 0 0
Guangzhou
Country [10] 0 0
China
State/province [10] 0 0
Hohhot
Country [11] 0 0
China
State/province [11] 0 0
Shanghai
Country [12] 0 0
France
State/province [12] 0 0
Lille Cedex
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Nice
Country [15] 0 0
France
State/province [15] 0 0
Rouen Cedex
Country [16] 0 0
Germany
State/province [16] 0 0
Bad Bentheim
Country [17] 0 0
Germany
State/province [17] 0 0
Bielefeld
Country [18] 0 0
Germany
State/province [18] 0 0
Dresden
Country [19] 0 0
Germany
State/province [19] 0 0
Leipzig
Country [20] 0 0
Greece
State/province [20] 0 0
Thessaloniki
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Israel
State/province [22] 0 0
Tel-Aviv
Country [23] 0 0
Italy
State/province [23] 0 0
Catania
Country [24] 0 0
Italy
State/province [24] 0 0
Florence
Country [25] 0 0
Italy
State/province [25] 0 0
Rome
Country [26] 0 0
Japan
State/province [26] 0 0
Iruma-Gun
Country [27] 0 0
Japan
State/province [27] 0 0
Kitakyusyu-shi
Country [28] 0 0
Japan
State/province [28] 0 0
Kurume-shi
Country [29] 0 0
Japan
State/province [29] 0 0
Okayama
Country [30] 0 0
Japan
State/province [30] 0 0
Ota-ku
Country [31] 0 0
Japan
State/province [31] 0 0
Sapporo-shi
Country [32] 0 0
Japan
State/province [32] 0 0
Urayasu-shi
Country [33] 0 0
Spain
State/province [33] 0 0
Alicante
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.