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

Study Overview
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Brief Summary
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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

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

Conditions
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Bullous Pemphigoid

Intervention / Treatment
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* Drug: dupilumab
* Drug: Matching Placebo
* Drug: Oral corticosteroids (OCS)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving sustained remission |  | Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total cumulative dose of oral corticosteroids (OCS) |  | Baseline to week 36 | 
| 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 | 
| Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4 |  | Baseline to week 36 | 
| 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 |