Clinical trial NCT04206553: A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bullous Pemphigoid
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2019-12-20
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to investigate whether dupilumab is effective and safe for the treatment of bullous pemphigoid. Dupilumab is a type of drug called a "monoclonal antibody". An antibody is a special kind of protein that the immune (defense) system normally makes to fight bacteria and viruses. Bullous pemphigoid is an autoimmune subepidermal blistering disease, predominately affecting the elderly (typical onset after age 60).

The study is looking at several other research questions, including:

* Side effects that may be experienced by people taking dupilumab
* How dupilumab works in the body and affects the body
* How dupilumab affects quality of life
* How much dupilumab is present in the blood
* To see if dupilumab works to wean the patient off oral corticosteroids


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients achieving sustained remission
timeFrame: Week 36
Secondary outcomes:
measure: Total cumulative dose of oral corticosteroids (OCS)
timeFrame: Baseline to week 36
measure: Percent change in weekly average of daily peak pruritus numerical rating score (NRS)
timeFrame: Baseline to week 36
measure: Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4
timeFrame: Baseline to week 36
measure: Percent change in Bullous Pemphigoid Disease Area Index Activity Score (BPDAI) activity score
timeFrame: Baseline to week 36
measure: Time to first use of rescue medication
timeFrame: Up to week 36
Other outcomes:
measure: Duration of complete remission while not requiring OCS
timeFrame: Baseline to week 36
measure: Proportion of patients who do not achieve control of disease activity, who relapse after achieving control of disease activity, or do not achieve complete remission
timeFrame: Baseline to week 36
measure: Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75%, and 90%
timeFrame: Baseline to week 36
measure: Change in autoimmune bullous disease quality of life (ABQOL)
timeFrame: Baseline to week 36
measure: Change in percent body surface area (BSA) of BP involvement
timeFrame: Baseline to week 36
measure: Change in BP180 autoantibody (IgG) titers
timeFrame: Baseline to week 36
measure: Change in BP230 autoantibody (IgG) titers
timeFrame: Baseline to week 36
measure: Proportion of patients with sustained remission
timeFrame: Week 52
measure: Total cumulative dose of OCS
timeFrame: Baseline to week 52
measure: Duration of complete remission while not requiring OCS
timeFrame: Up to week 52
measure: Proportion of patients who do not achieve control of disease activity, who relapse after achieving control of disease activity, or do not achieve complete remission
timeFrame: Up to week 52
measure: Percent change in weekly average of daily peak pruritus NRS
timeFrame: Baseline to week 52
measure: Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4
timeFrame: Baseline to week 52
measure: Percent change in BPDAI activity score
timeFrame: Baseline to week 52
measure: Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75% and 90%
timeFrame: Baseline to week 52
measure: Change in ABQOL
timeFrame: Baseline to week 52
measure: Change in percent BSA of BP involvement
timeFrame: Baseline to week 52
measure: Change in BP180 autoantibody (IgG) titers
timeFrame: Baseline to week 52
measure: Change in BP230 autoantibody (IgG) titers
timeFrame: Baseline to week 52
measure: Proportion of patients in complete remission and off OCS
timeFrame: Week 16
measure: Percent change in BPDAI activity score
timeFrame: Baseline to week 16
measure: Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75%, and 90%
timeFrame: Baseline to week 16
measure: Percent change in weekly average of daily peak pruritus NRS
timeFrame: Baseline to week 16
measure: Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4
timeFrame: Baseline to week 16
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Baseline to week 64
measure: Incidence of treatment-emergent serious adverse events (SAEs)
timeFrame: Baseline to week 64
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Baseline to week 64
measure: Concentrations of functional dupilumab in serum
timeFrame: Baseline to week 64
measure: Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer
timeFrame: Baseline to week 64
Locations:
city: Birmingham
country: United States
facility: Regeneron study Site
state: Alabama
city: Scottsdale
country: United States
facility: Regeneron Study Site
state: Arizona
city: Redwood City
country: United States
facility: Regeneron Study Site
state: California
city: Farmington
country: United States
facility: Regeneron Study Site
state: Connecticut
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Orlando
country: United States
facility: Regeneron study Site
state: Florida
city: Iowa City
country: United States
facility: Regeneron Study Site
state: Iowa
city: Boston
country: United States
facility: Regeneron Study Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Regeneron study Site
state: Michigan
city: Chapel Hill
country: United States
facility: Regeneron Study Site
state: North Carolina
city: Portland
country: United States
facility: Regeneron Study Site
state: Oregon
city: Philadelphia
country: United States
facility: Regeneron Study Site
state: Pennsylvania
city: Providence
country: United States
facility: Regeneron study Site
state: Rhode Island
city: Murray
country: United States
facility: Regeneron Study Site
state: Utah
city: Charlottesville
country: United States
facility: Regeneron study Site
state: Virginia
city: Kogarah
country: Australia
facility: Regeneron Study Site
state: New South Wales
city: Box Hill
country: Australia
facility: Regeneron Study Site
state: Victoria
city: Bobigny
country: France
facility: Regeneron Study Site
city: Bordeaux
country: France
facility: Regeneron Study Site
city: Lille
country: France
facility: Regeneron Study Site
city: Nice
country: France
facility: Regeneron Study Site
city: Paris
country: France
facility: Regeneron Study Site
city: Rouen Cedex
country: France
facility: Regeneron Study Site
city: Muenster
country: Germany
facility: Regeneron Study Site
state: North Rhine-Westphal
city: Mainz
country: Germany
facility: Regeneron Study Site
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Regeneron Study Site 2
state: Saxony
city: Luebeck
country: Germany
facility: Regeneron Study Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Regeneron Study Site
city: Buxtehude
country: Germany
facility: Regeneron Study Site
city: Erlangen
country: Germany
facility: Regeneron Study Site
city: Freiburg
country: Germany
facility: Regeneron Study Site
city: Magdeburg
country: Germany
facility: Regeneron Study site'
city: Marburg
country: Germany
facility: Regeneron Study site
city: Munich
country: Germany
facility: Regeneron Study Site
city: Stuttgart
country: Germany
facility: Regeneron Study Site
city: Afula
country: Israel
facility: Regeneron study Site
city: Petah Tikva
country: Israel
facility: Regeneron study Site
city: Tel-Aviv
country: Israel
facility: Regeneron study Site
city: Kurume
country: Japan
facility: Regeneron Study site
state: Hukuoka
city: Hirosaki
country: Japan
facility: Regeneron Study Site
city: Ichinomiya
country: Japan
facility: Regeneron Study Site
city: Osaka
country: Japan
facility: Regeneron Study Site
city: Sapporo
country: Japan
facility: Regeneron Study Site
city: Tokyo
country: Japan
facility: Regeneron Study Site
city: Krakow
country: Poland
facility: Regeneron Study Site
state: Malopolskie
city: Ossy
country: Poland
facility: Regeneron Study site'
city: Wroclaw
country: Poland
facility: Regeneron Study site'
city: Badalona
country: Spain
facility: Regeneron Study Site
state: Barcelona
city: Madrid
country: Spain
facility: Regeneron Study Site
city: Madrid
country: Spain
facility: Regeneron study Site
city: Pamplona
country: Spain
facility: Regeneron study Site
city: Taipei
country: Taiwan
facility: Regeneron study Site
state: Zhongzheng District
city: Taoyuan City
country: Taiwan
facility: Regeneron study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: