NCT04206553CompletedPhase 2
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients With Bullous Pemphigoid
Regeneron Pharmaceuticals56 sites in 8 countries106 target enrollmentStarted: October 28, 2020Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 106
- Locations
- 56
- Primary Endpoint
- Percent of Participants Achieving Sustained Remission at Week 36
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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
Arms & Interventions
dupilumab
Experimental
Intervention: Oral corticosteroids (OCS) (Drug)
Matching placebo
Experimental
Intervention: Matching Placebo (Drug)
Matching placebo
Experimental
Intervention: Oral corticosteroids (OCS) (Drug)
dupilumab
Experimental
Intervention: dupilumab (Drug)
Outcomes
Primary Outcomes
Percent of Participants Achieving Sustained Remission at Week 36
Time Frame: 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 Outcomes
- 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)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 36(Baseline, Week 36)
- Total Cumulative Dose of Oral Corticosteroids (OCS) From Baseline to Week 36(Week 36)
- Percent Change in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 36(Baseline, Week 36)
- Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 36(Baseline, Week 36)
- Percent Change in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score From Baseline to Week 36(Baseline, Week 36)
- Time to First Use of Rescue Medication Up to Week 36(Up to Week 36)
- Duration of Complete Remission While Not Requiring OCS Up to Week 36(Up to Week 36)
- Percent of Participants Who Did Not Achieve 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(Up to Week 36)
- Percent of Participants Who Did Not Achieve Complete Remission Before Week 36(Up to Week 36)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 36(Baseline, Week 36)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 36(Baseline, Week 36)
- Change in Autoimmune Bullous Disease Quality of Life (ABQOL) Score From Baseline to Week 36(Baseline, Week 36)
- Change in Percent Body Surface Area (BSA) of BP Involvement From Baseline to Week 36(Baseline, Week 36)
- Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 52(Baseline, Week 52)
- Change in BP180 Immunoglobulin G (IgG) Autoantibody Titer From Baseline to Week 36(Baseline, Week 36)
- Change in BP230 IgG Autoantibody Titer From Baseline to Week 36(Baseline, Week 36)
- Percent of Participants Achieving Sustained Remission at Week 52(At Week 52)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 52(Baseline, Week 52)
- Percent of Participants Who Did Not Achieve Complete Remission Before Week 52(Up to Week 52)
- Total Cumulative Dose of OCS From Baseline to Week 52(Week 52)
- Duration of Complete Remission While Not Requiring OCS Up to Week 52(Up to Week 52)
- Percent of Participants Who Did Not Achieve 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(Up to Week 52)
- Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 52(Baseline, Week 52)
- Percent Change in BPDAI Activity Score From Baseline to Week 52(Baseline, Week 52)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 52(Baseline, Week 52)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 52(Baseline, Week 52)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥90% From Baseline to Week 16(Baseline, Week 16)
- Change in ABQOL Score From Baseline to Week 52(Baseline, Week 52)
- Change in Percent BSA of BP Involvement From Baseline to Week 52(Baseline, Week 52)
- Change in BP180 IgG Autoantibody Titer From Baseline to Week 52(Baseline, Week 52)
- Number of Participants With At Least One TEAE Through Week 64(Week 52 through Week 64)
- Percent Change in Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16(Baseline, Week 16)
- Change in BP230 IgG Autoantibody Titer From Baseline to Week 52(Baseline, Week 52)
- Percent of Participants in Complete Remission and Off OCS No Later Than Week 16(Up to Week 16)
- Percent Change in BPDAI Activity Score From Baseline to Week 16(Baseline, Week 16)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥50% From Baseline to Week 16(Baseline, Week 16)
- Percent of Participants Achieving a Reduction in BPDAI Activity Score of ≥75% From Baseline to Week 16(Baseline, Week 16)
- Percent of Participants With Improvement (Reduction) of Weekly Average of Daily Peak Pruritus NRS ≥4 From Baseline to Week 16(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)
Investigators
Study Sites (56)
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