A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid (LIBERTY-BP)

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

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

Study Overview

• Status: Completed
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Drug: dupilumab; Drug: Oral corticosteroids (OCS); Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Regeneron Study Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Regeneron Study Site
• France
  • Bobigny, France, 93009
    • Regeneron Study Site
  • Bordeaux, France, 33000
    • Regeneron Study Site
  • Lille, France, 59037
    • Regeneron Study Site
  • Nice, France, 06200
    • Regeneron Study Site
  • Paris, France, 75010
    • Regeneron Study Site
  • Rouen, France, 76031
    • Regeneron Study Site
• Germany
  • Berlin, Germany, 10117
    • Regeneron Study Site
  • Buxtehude, Germany, 21614
    • Regeneron Study Site
  • Erlangen, Germany, 91054
    • Regeneron Study Site
  • Freiburg im Breisgau, Germany, 79104
    • Regeneron Study Site
  • Magdeburg, Germany, 39120
    • Regeneron Study site'
  • Marburg, Germany, 35043
    • Regeneron Study Site
  • Munich, Germany, 80802
    • Regeneron Study Site
  • Stuttgart, Germany, 70178
    • Regeneron Study Site
  • North Rhine-Westphal
    • Münster, North Rhine-Westphal, Germany, 48149
      • Regeneron Study Site
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Regeneron Study Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Regeneron Study Site 2
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Regeneron Study Site
• Israel
  • Afula, Israel, 1834111
    • Regeneron Study Site
  • Petah Tikva, Israel, 49100
    • Regeneron Study Site
  • Tel Aviv, Israel, 6423906
    • Regeneron Study Site
• Japan
  • Hirosaki, Japan, 036-8563
    • Regeneron Study Site
  • Ichinomiya, Japan, 491-8558
    • Regeneron Study Site
  • Osaka, Japan, 545-8586
    • Regeneron Study Site
  • Sapporo, Japan, 060-8648
    • Regeneron Study Site
  • Tokyo, Japan, 160-8582
    • Regeneron Study Site
  • Hukuoka
    • Kurume, Hukuoka, Japan, 830-0011
      • Regeneron Study Site
• Poland
  • Ossy, Poland, 42-624
    • Regeneron Study site'
  • Wroclaw, Poland, 50566
    • Regeneron Study site'
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-147
      • Regeneron Study Site
• Spain
  • Madrid, Spain, 28034
    • Regeneron Study Site
  • Madrid, Spain, 28046
    • Regeneron Study Site
  • Pamplona, Spain, 31008
    • Regeneron Study Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Regeneron Study Site
• Taiwan
  • Taoyuan, Taiwan, 33305
    • Regeneron Study Site
  • Zhongzheng District
    • Taipei, Zhongzheng District, Taiwan, 10002
      • Regeneron Study Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Regeneron Study Site
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Regeneron Study Site
  • California
    • Redwood City, California, United States, 94063
      • Regeneron Study Site
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Regeneron Study Site
  • Florida
    • Miami, Florida, United States, 33125
      • Regeneron Study Site
    • Orlando, Florida, United States, 32827
      • Regeneron Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Regeneron Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Regeneron Study Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5314
      • Regeneron Study Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Regeneron Study Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Regeneron Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Regeneron Study Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Regeneron Study Site
  • Utah
    • Murray, Utah, United States, 84107
      • Regeneron Study Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dupilumab	Drug: dupilumab; Loading dose administered subcutaneous (SC), followed by SC once every 2 weeks (Q2W) dosing.; Other Names: REGN668; SAR231893; Dupixent®; Drug: Oral corticosteroids (OCS); Prednisone or prednisolone per standard of care to obtain control of disease activity.
Experimental: Matching placebo	Drug: Oral corticosteroids (OCS); Prednisone or prednisolone per standard of care to obtain control of disease activity.; Drug: Matching Placebo; Matching dupilumab without active substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Achieving Sustained Remission at Week 36	Sustained remission at week 36, defined as: (1) Complete remission (absence of new lesions & epithelialization of old lesions) & off oral corticosteroids (OCS) no later than week 16 & (2) Absence of disease relapse (appearance of ≥3 new lesions a month [blisters, eczematous lesions, or urticarial plaques] or at least 1 large eczematous lesion or urticarial plaque that does not heal within 1 week) after completion of OCS taper, no later than week 16, to week 36 & (3) Absence of need for rescue therapy during 36 weeks (rescue therapy includes increase of OCS dose during the taper, re-initiation of OCS after completion of the OCS taper, or initiation of any BP-directed therapy). Participants with missing sustained remission data at week 36 due to discontinuation due to lack of efficacy, treatment-related AE, or death were considered non-responders & those with missing data due to other reasons were handled using multiple imputation.	At Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Cumulative Dose of Oral Corticosteroids (OCS) From Baseline to Week 36	All participants in both treatment groups were started on OCS at randomization (day 1) with taper beginning no later than week 6 with the objective to taper off by week 16. OCS could be used as rescue treatment for loss of disease control/ disease relapse during the study. Days after non-OCS systemic rescue treatment use were imputed by the worst observation carried forward (WOCF) method (i.e., the highest daily OCS dose prior to any non-OCS systemic rescue treatment use). Missing data after study discontinuation were imputed with the average daily OCS dose among week 36 completers in each treatment group.	Week 36
Percent Change in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 36	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 36	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 36 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the weekly average of daily peak pruritus NRS.	Baseline, Week 36
Percent Change in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score From Baseline to Week 36	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Time to First Use of Rescue Medication Up to Week 36	Participants were considered to have used rescue treatment at the time of discontinuation from the study due to lack of efficacy, treatment-related AE, or death. Participants were censored at the time of discontinuation from the study due to other reasons. Restricted mean event time and corresponding standard error (SE) are based on the Kaplan-Meier method. The restricted mean event time was calculated up to study day 253 (i.e., week 36).	Up to Week 36
Duration of Complete Remission While Not Requiring OCS Up to Week 36	Complete remission was defined as absence of new lesions and epithelialization of old lesions. Participants were considered as not achieving complete remission after rescue treatment use. Participants with missing assessment of complete remission caused by discontinuation from the study before week 36 due to lack of efficacy, treatment-related AE, or death were considered as not achieving complete remission. Participants with missing assessment of complete remission due to other reasons were imputed using multiple imputation.	Up to Week 36
Percent of Participants Who Did Not Achieve Control of Disease Activity Before Week 36	Control of disease activity was defined as absence of new lesions and existing lesions beginning to heal. Participants who achieved initial control of disease activity after rescue treatment use were considered to not have achieved control of disease activity before week 36. Participants whose response status could not be determined due to missing data were considered to not have achieved control of disease activity before week 36.	Up to Week 36
Percent of Participants Who Relapsed After Achieving Control of Disease Activity Up to Week 36	Relapse was defined as the appearance of 3 or more new lesions a month (blisters, eczematous lesions, or urticarial plaques) or at least 1 large (>10 centimeters [cm] diameter) eczematous lesion or urticarial plaque that does not heal within 1 week. Control of disease activity was defined as absence of new lesions and existing lesions beginning to heal. Participants who used rescue treatment were considered to have relapsed after achieving control of disease activity. Participants whose response status could not be determined due to missing data were considered to have relapsed after achieving control of disease activity.	Up to Week 36
Percent of Participants Who Did Not Achieve Complete Remission Before Week 36	Complete remission was defined as absence of new lesions and epithelialization of old lesions. Participants who achieved initial complete remission after rescue treatment use were considered to not have achieved complete remission before week 36. Participants whose response status could not be determined due to missing data were considered to not have achieved complete remission before week 36.	Up to Week 36
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 36	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 36 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 36
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 36	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 36 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 36
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 36	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 36 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 36
Change in Autoimmune Bullous Disease Quality of Life (ABQOL) Score From Baseline to Week 36	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. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Change in Percent Body Surface Area (BSA) of BP Involvement From Baseline to Week 36	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Change in BP180 Immunoglobulin G (IgG) Autoantibody Titer From Baseline to Week 36	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Change in BP230 IgG Autoantibody Titer From Baseline to Week 36	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 36
Percent of Participants Achieving Sustained Remission at Week 52	Sustained remission at week 52, defined as: (1) Complete remission (absence of new lesions & epithelialization of old lesions) & off OCS no later than week 16 & (2) Absence of disease relapse (appearance of ≥3 new lesions a month [blisters, eczematous lesions, or urticarial plaques] or at least 1 large eczematous lesion or urticarial plaque that does not heal within 1 week) after completion of OCS taper, no later than week 16, to week 52 & (3) Absence of need for rescue therapy during 52 weeks (rescue therapy includes increase of OCS dose during the taper, re-initiation of OCS after completion of the OCS taper, or initiation of any BP-directed therapy). Participants with missing sustained remission data at week 52 due to discontinuation due to lack of efficacy, treatment-related AE, or death were considered non-responders & those with missing data due to other reasons were handled using multiple imputation.	At Week 52
Total Cumulative Dose of OCS From Baseline to Week 52	All participants in both treatment groups were started on OCS at randomization (day 1) with taper beginning no later than week 6 with the objective to taper off by week 16. OCS could be used as rescue treatment for loss of disease control/ disease relapse during the study. Days after non-OCS systemic rescue treatment use were imputed by the WOCF method (i.e., the highest daily OCS dose prior to any non-OCS systemic rescue treatment use). Missing data after study discontinuation were imputed with the average daily OCS dose among week 52 completers in each treatment group.	Week 52
Duration of Complete Remission While Not Requiring OCS Up to Week 52	Complete remission was defined as absence of new lesions and epithelialization of old lesions. Participants were considered as not achieving complete remission after rescue treatment use. Participants with missing assessment of complete remission caused by discontinuation from the study before week 52 due to lack of efficacy, treatment-related AE, or death were considered as not achieving complete remission. Participants with missing assessment of complete remission due to other reasons were imputed using multiple imputation.	Up to Week 52
Percent of Participants Who Did Not Achieve Control of Disease Activity Before Week 52	Control of disease activity was defined as absence of new lesions and existing lesions beginning to heal. Participants who achieved initial control of disease activity after rescue treatment use were considered to not have achieved control of disease activity before week 52. Participants whose response status could not be determined due to missing data were considered to not have achieved control of disease activity before week 52.	Up to Week 52
Percent of Participants Who Relapsed After Achieving Control of Disease Activity Up to Week 52	Relapse was defined as the appearance of 3 or more new lesions a month (blisters, eczematous lesions, or urticarial plaques) or at least 1 large (>10 cm diameter) eczematous lesion or urticarial plaque that does not heal within 1 week. Control of disease activity was defined as absence of new lesions and existing lesions beginning to heal. Participants who used rescue treatment were considered to have relapsed after achieving control of disease activity. Participants whose response status could not be determined due to missing data were considered to have relapsed after achieving control of disease activity.	Up to Week 52
Percent of Participants Who Did Not Achieve Complete Remission Before Week 52	Complete remission was defined as absence of new lesions and epithelialization of old lesions. Participants who achieved initial complete remission after rescue treatment use were considered to not have achieved complete remission before week 52. Participants whose response status could not be determined due to missing data were considered to not have achieved complete remission before week 52.	Up to Week 52
Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 52	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 52	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 52 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the weekly average of daily peak pruritus NRS.	Baseline, Week 52
Percent Change in BPDAI Activity Score From Baseline to Week 52	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 52	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 52 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 52
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 52	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 52 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 52
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 52	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 52 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 52
Change in ABQOL Score From Baseline to Week 52	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. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Change in Percent BSA of BP Involvement From Baseline to Week 52	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Change in BP180 IgG Autoantibody Titer From Baseline to Week 52	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Change in BP230 IgG Autoantibody Titer From Baseline to Week 52	Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 52. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 52
Percent of Participants in Complete Remission and Off OCS No Later Than Week 16	Complete remission was defined as absence of new lesions and epithelialization of old lesions. Participants were considered non-responders after rescue treatment use. Participants with missing assessment of complete remission caused by discontinuation from the study before week 16 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Participants with missing assessment of complete remission before week 16 due to other reasons were imputed using multiple imputation.	Up to Week 16
Percent Change in BPDAI Activity Score From Baseline to Week 16	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 16
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 16	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 16 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 16
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 16	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 16 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 16
Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 16	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. Participants were required to have a BPDAI activity score of ≥24 at the screening and baseline visits for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 16 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the BPDAI activity score.	Baseline, Week 16
Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Values after first rescue treatment were set to missing and were imputed with the worst value from the closest visit on or prior to rescue medication use and afterwards up to and including week 36. Missing values caused by discontinuation from the study due to lack of efficacy, treatment-related AE, or death were imputed by the WOCF method. Missing values due to other reasons were imputed by multiple imputation.	Baseline, Week 16
Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 16	Peak pruritus NRS was used by participants to rate the intensity of pruritus during the past 24 hours, with 0 indicating no itch and 10 indicating worst itch possible. Participants were required to have a baseline peak pruritus NRS maximum intensity average of ≥4 during the 7 days prior to randomization for eligibility. Participants were considered non-responders after rescue treatment use. Participants with missing values caused by discontinuation from the study before week 16 due to lack of efficacy, treatment-related AE, or death were considered non-responders. Missing values due to other reasons were imputed using multiple imputation of the continuous data of the weekly average of daily peak pruritus NRS.	Baseline, Week 16
Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) Through Week 52		Through Week 52
Number of Participants With At Least One Serious TEAE Through Week 52		Through Week 52
Number of Participants With At Least One TE Adverse Event of Special Interest (AESI) Through Week 52		Through Week 52
Number of Participants With At Least One TEAE Through Week 64		Week 52 through Week 64
Number of Participants With At Least One Serious TEAE Through Week 64		Week 52 through Week 64
Number of Participants With At Least One TE AESI Through Week 64		Week 52 through Week 64
Concentrations of Functional Dupilumab in Serum		Baseline to Week 64
Number of Participants With TE Anti-drug Antibody (ADA) Response Per Maximum Titer Category		Baseline to Week 64

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supplemental Analysis of Total Cumulative Dose of OCS From Baseline to Week 36	All participants in both treatment groups were started on OCS at randomization (day 1) with taper beginning no later than week 6 with the objective to taper off by week 16. OCS could be used as rescue treatment for loss of disease control/ disease relapse during the study. Days after non-OCS systemic rescue treatment use were imputed by the WOCF method (i.e., the highest daily OCS dose prior to any non-OCS systemic rescue treatment use). Missing data after study discontinuation were imputed with the average daily OCS dose among week 36 completers in each treatment group. Median total cumulative dose of OCS from baseline to week 36 reported.	Week 36

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Murrell DF, Joly P, Werth VP, Ujiie H, Worm M, Mangold AR, Avetisova E, Maloney J, Laws E, Mortensen E, Dubost-Brama A, Shabbir A. Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT. Adv Ther. 2024 Jul;41(7):2991-3002. doi: 10.1007/s12325-024-02810-3. Epub 2024 Mar 5.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): July 12, 2024
• Study Completion (Actual): January 5, 2025

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vesiculobullous; Skin and Connective Tissue Diseases; Pemphigoid, Bullous; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; dupilumab; Adrenal Cortex Hormones
• Other Study ID Numbers: R668-BP-1902; 2019-003520-20 (EudraCT Number); 2024-510745-34-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No