A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid

Bullous Pemphigoid Clinical Trial

— LIBERTY-BP  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04206553
• Other study ID #: R668-BP-1902
• Secondary ID: 2019-003520-20
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: October 28, 2020
• Est. completion date: January 7, 2025

Study information

• Verified date: November 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to demonstrate that dupilumab is superior to placebo in achieving sustained remission off oral corticosteroids (OCS) in patients with bullous pemphigoid (BP). The secondary objectives of the study are: - To evaluate the OCS-sparing effects of dupilumab in patients with BP - To evaluate the effect of dupilumab on itch in patients with BP - To evaluate the effects of dupilumab on health-related quality of life measures in patients with BP - To evaluate the effect of dupilumab in circulating BP180 and BP230 autoantibody titers - To assess the safety and tolerability of dupilumab administered to patients with BP - To characterize the trough concentrations of functional dupilumab over time following administration of dupilumab in patients with BP - To assess the immunogenicity of dupilumab in patients with BP over time

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: January 7, 2025
• Est. primary completion date: October 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Key Inclusion Criteria:

• Patients must have characteristic clinical features of bullous pemphigoid (BP) (eg, urticarial or eczematous or erythematous plaques, bullae, pruritus) at the screening and baseline visits.
• Study participants are required to have a confirmed diagnosis of BP based on histopathology, immunopathology, and serology at the baseline visit, as defined in the protocol.
• Bullous Pemphigoid Disease Area Index (BPDAI) activity score =24 at baseline and screening visits.
• Baseline peak pruritus NRS score for maximum itch intensity =4
• Karnofsky performance status score =50% at the screening visit.

Key Exclusion Criteria:

• Forms of pemphigoid other than classic BP (eg, Brunsting-Perry cicatricial pemphigoid, anti-p200 pemphigoid, epidermolysis bullosa acquisita, or BP with concomitant pemphigus vulgaris)
• Patients who are receiving treatments known to cause or exacerbate BP (eg, angiotensin converting enzyme inhibitors, penicillamine, furosemide, phenacetin, dipeptidyl peptidase 4 inhibitor) who have not been on a stable dose of these medications for at least 4 weeks prior to the screening visit
• Have ever received treatment with an IL-4 or IL-13 antagonist such as dupilumab, tralokinumab, or lebrikizumab.
• Treatment with systemic corticosteroids within 7 days before the baseline visit
• Treatment with topical corticosteroids of medium potency or higher, topical calcineurin inhibitor, or topical crisaborole within 7 days before the baseline visit
• Treatment with non-steroidal immunosuppressive/immunomodulating drug(s) (eg, mycophenolate mofetil, azathioprine, or methotrexate) within 4 weeks before the baseline visit.
• Treatment with BP-directed biologics as follows:
• Any cell-depleting agents including but not limited to rituximab: within 12 months before the baseline visit, or until lymphocyte and CD 19+ lymphocyte count returns to normal, whichever is longer
• Other biologics (such as IL-5 inhibitors benralizumab or mepolizumab): within 5 half-lives (if known) or 16 weeks prior to the baseline visit, whichever is longer
• Intravenous immunoglobulin within 16 weeks prior to the baseline visit NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Related Conditions & MeSH terms

• Bullous Pemphigoid
• Pemphigoid, Bullous

Intervention

Drug:
• dupilumab
Loading dose administered subcutaneous (SC), followed by SC once every 2 weeks (Q2W) dosing.
• Matching Placebo
Matching dupilumab without active substance
• Oral corticosteroids (OCS)
Prednisone or prednisolone per standard of care to obtain control of disease activity.

Locations

Country	Name	City	State
Australia	Regeneron Study Site	Box Hill	Victoria
Australia	Regeneron Study Site	Kogarah	New South Wales
France	Regeneron Study Site	Bobigny
France	Regeneron Study Site	Bordeaux
France	Regeneron Study Site	Lille
France	Regeneron Study Site	Nice
France	Regeneron Study Site	Paris
France	Regeneron Study Site	Rouen Cedex
Germany	Regeneron Study Site	Berlin
Germany	Regeneron Study Site	Buxtehude
Germany	Regeneron Study Site 2	Dresden	Saxony
Germany	Regeneron Study Site	Erlangen
Germany	Regeneron Study Site	Freiburg
Germany	Regeneron Study Site	Luebeck	Schleswig-Holstein
Germany	Regeneron Study site'	Magdeburg
Germany	Regeneron Study Site	Mainz	Rheinland-Pfalz
Germany	Regeneron Study site	Marburg
Germany	Regeneron Study Site	Muenster	North Rhine-Westphal
Germany	Regeneron Study Site	Munich
Germany	Regeneron Study Site	Stuttgart
Israel	Regeneron study Site	Afula
Israel	Regeneron study Site	Petah Tikva
Israel	Regeneron study Site	Tel-Aviv
Japan	Regeneron Study Site	Hirosaki
Japan	Regeneron Study Site	Ichinomiya
Japan	Regeneron Study site	Kurume	Hukuoka
Japan	Regeneron Study Site	Osaka
Japan	Regeneron Study Site	Sapporo
Japan	Regeneron Study Site	Tokyo
Poland	Regeneron Study Site	Krakow	Malopolskie
Poland	Regeneron Study site'	Ossy
Poland	Regeneron Study site'	Wroclaw
Spain	Regeneron Study Site	Badalona	Barcelona
Spain	Regeneron Study Site	Madrid
Spain	Regeneron study Site	Madrid
Spain	Regeneron study Site	Pamplona
Taiwan	Regeneron study Site	Taipei	Zhongzheng District
Taiwan	Regeneron study Site	Taoyuan City
United States	Regeneron study Site	Ann Arbor	Michigan
United States	Regeneron study Site	Birmingham	Alabama
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Chapel Hill	North Carolina
United States	Regeneron study Site	Charlottesville	Virginia
United States	Regeneron Study Site	Farmington	Connecticut
United States	Regeneron Study Site	Iowa City	Iowa
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Murray	Utah
United States	Regeneron study Site	Orlando	Florida
United States	Regeneron Study Site	Philadelphia	Pennsylvania
United States	Regeneron Study Site	Portland	Oregon
United States	Regeneron study Site	Providence	Rhode Island
United States	Regeneron Study Site	Redwood City	California
United States	Regeneron Study Site	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Israel,  Japan,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of complete remission while not requiring OCS		Baseline to week 36
Other	Proportion of patients who do not achieve control of disease activity or who relapse after achieving control of disease activity	Note: control of disease activity is defined when new lesions cease to form and existing lesions begin to heal	Baseline to week 36
Other	Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75%, and 90%		Baseline to week 36
Other	Change in autoimmune bullous disease quality of life (ABQOL)	ABQOL questionnaire consists of 17 items, which encompass physical burden of the disease, psychiatric effects, and effects on daily life functioning. Each question ranges from 0 to 3 points, with higher scores indicating poorer quality of life. The maximum ABQOL score is 51.	Baseline to week 36
Other	Change in percent body surface area (BSA) of BP involvement		Baseline to week 36
Other	Change in BP180 autoantibody (IgG) titers		Baseline to week 36
Other	Change in BP230 autoantibody (IgG) titers		Baseline to week 36
Other	Proportion of patients with sustained remission		Week 52
Other	Total cumulative dose of OCS		Baseline to week 52
Other	Duration of complete remission while not requiring OCS		Up to week 52
Other	Proportion of patients who do not achieve control of disease activity or who relapse after achieving control of disease activity		Up to week 52
Other	Percent change in weekly average of daily peak pruritus NRS		Baseline to week 52
Other	Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS =4		Baseline to week 52
Other	Percent change in BPDAI activity score		Baseline to week 52
Other	Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75% and 90%		Baseline to week 52
Other	Change in ABQOL		Baseline to week 52
Other	Change in percent BSA of BP involvement		Baseline to week 52
Other	Change in BP180 autoantibody (IgG) titers		Baseline to week 52
Other	Change in BP230 autoantibody (IgG) titers		Baseline to week 52
Other	Proportion of patients in complete remission and off OCS		Week 16
Other	Percent change in BPDAI activity score		Baseline to week 16
Other	Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75%, and 90%		Baseline to week 16
Other	Percent change in weekly average of daily peak pruritus NRS		Baseline to week 16
Other	Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS =4		Baseline to week 16
Other	Incidence of treatment-emergent adverse events (TEAEs)		Baseline to week 64
Other	Incidence of treatment-emergent serious adverse events (SAEs)		Baseline to week 64
Other	Incidence of adverse events of special interest (AESIs)		Baseline to week 64
Other	Concentrations of functional dupilumab in serum		Baseline to week 64
Other	Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer		Baseline to week 64
Primary	Proportion of patients achieving sustained remission		Week 36
Secondary	Total cumulative dose of oral corticosteroids (OCS)		Baseline to week 36
Secondary	Percent change in weekly average of daily peak pruritus numerical rating score (NRS)	Individual NRS used to rate the intensity of pruritus using an 11-point scale (0 to 10) in which 0 indicates no itch while 10 indicates worst itch possible.	Baseline to week 36
Secondary	Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS =4		Baseline to week 36
Secondary	Percent change in Bullous Pemphigoid Disease Area Index Activity Score (BPDAI) activity score	BPDAI activity score is the arithmetic sum of 3 subcomponents: cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. Scores can range from 0 to 360 for BPDAI total activity (maximum 240 for total skin activity and 120 for mucosal activity), with higher scores indicating greater disease activity.	Baseline to week 36