Bullous Pemphigoid
Conditions
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
Interventions
DRUGdupilumab
Loading dose administered subcutaneous (SC), followed by SC once every 2 weeks (Q2W) dosing.
DRUGMatching Placebo
Matching dupilumab without active substance
DRUGOral corticosteroids (OCS)
Prednisone or prednisolone per standard of care to obtain control of disease activity.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Achieving Sustained Remission at Week 36 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Cumulative Dose of Oral Corticosteroids (OCS) From Baseline to Week 36 | 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. |
| Percent Change in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 36 | Baseline, 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. |
| Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 36 | Baseline, 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. |
| Percent Change in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score From Baseline to Week 36 | Baseline, 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. |
| Time to First Use of Rescue Medication Up to Week 36 | 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). |
| Duration of Complete Remission While Not Requiring OCS Up to Week 36 | 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. |
| Percent of Participants Who Did Not Achieve Control of Disease Activity Before Week 36 | Up to 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. |
| Percent of Participants Who Relapsed After Achieving Control of Disease Activity Up to Week 36 | 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. |
| Percent of Participants Who Did Not Achieve Complete Remission Before Week 36 | Up to 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 36 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 36 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 36 | Baseline, 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. |
| Change in Autoimmune Bullous Disease Quality of Life (ABQOL) Score From Baseline to Week 36 | Baseline, 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. |
| Change in Percent Body Surface Area (BSA) of BP Involvement From Baseline to Week 36 | Baseline, 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. |
| Change in BP180 Immunoglobulin G (IgG) Autoantibody Titer From Baseline to Week 36 | Baseline, 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. |
| Change in BP230 IgG Autoantibody Titer From Baseline to Week 36 | Baseline, 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. |
| Percent of Participants Achieving Sustained Remission at Week 52 | 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. |
| Total Cumulative Dose of OCS From Baseline to Week 52 | 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. |
| Duration of Complete Remission While Not Requiring OCS Up to Week 52 | 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. |
| Percent of Participants Who Did Not Achieve Control of Disease Activity Before Week 52 | Up to 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. |
| Percent of Participants Who Relapsed After Achieving Control of Disease Activity Up to Week 52 | 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. |
| Percent of Participants Who Did Not Achieve Complete Remission Before Week 52 | Up to 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. |
| Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 52 | Baseline, 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. |
| Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 52 | Baseline, 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. |
| Percent Change in BPDAI Activity Score From Baseline to Week 52 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 52 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 52 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 52 | Baseline, 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. |
| Change in ABQOL Score From Baseline to Week 52 | Baseline, 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. |
| Change in Percent BSA of BP Involvement From Baseline to Week 52 | Baseline, 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. |
| Change in BP180 IgG Autoantibody Titer From Baseline to Week 52 | Baseline, 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. |
| Change in BP230 IgG Autoantibody Titer From Baseline to Week 52 | Baseline, 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. |
| Percent of Participants in Complete Remission and Off OCS No Later Than Week 16 | Up to 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. |
| Percent Change in BPDAI Activity Score From Baseline to Week 16 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 16 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 16 | Baseline, 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. |
| Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 16 | Baseline, 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. |
| Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | Baseline, 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. |
| Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 16 | Baseline, 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. |
| 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 | — |
Countries
Australia, France, Germany, Israel, Japan, Poland, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Participant flow
Pre-assignment details
Of 163 participants screened, 106 participants were randomized and received study intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71.3 Years STANDARD_DEVIATION 9.72 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 85 Participants |
| Race/Ethnicity, Customized Not Reported | 8 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 35 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 53 | 2 / 53 |
| other Total, other adverse events | 49 / 53 | 43 / 53 |
| serious Total, serious adverse events | 21 / 53 | 20 / 53 |
Outcome results
None listed