Safety, Efficacy and PK/PD of QGE031 vs. Placebo in Patients With Active Bullous Pemphigoid Despite Oral Steroid Treatment

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of QGE031 versus placebo in patients with bullous pemphigoid. Efficacy will be assessed as a reduction of disease activity. How QGE031 is broken down by the body and the impact it has on different blood and tissue markers will also be explored.

Detailed Description
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This study was planned to be divided into 2 distinct parts. Part 1 was a multicenter, randomized, placebo-controlled study evaluating the efficacy, safety, PK and PD of multiple, subcutaneous doses of QGE031 in the treatment of patients with BP with disease refractory to oral steroid treatment. Patients were treated with QGE031 or placebo in a 2:1 ratio. Part 2 of this study was planned to be a multi-center, open label, dose range finding study evaluating the efficacy, safety, PK and PD of multiple, subcutaneous doses of QGE031 in the treatment of patients with BP with disease refractory to oral steroid treatment. This study was stopped after Part 1 completed and was terminated because the predefined criteria of efficacy was not reached ( >50% better then placebo)

Official Title
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A Randomized, Double-blind, Placebo Controlled, Parallel Group Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of QGE031 in the Treatment of Patients With Bullous Pemphigoid With Disease Refractory to Oral Steroid Treatment

Conditions
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Bullous Pemphigoid

Intervention / Treatment
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* Drug: QGE031
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with bullous pemphigoid Stable dose of prednisone at or above 10mg per day but no greater than 1 mg/kg/day Weigh between 40-120kg total IgE level up to 5000 IU/mL Exclusion Criteria: Use of rituximab within 1 year Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: QGE031<br>QGE031 240 mg Q2W s.c. | Drug: QGE031<br>* QGE031 will be evaluated at various dose levels and regimens, based on the impact on disease of the next highest dose level and regimen.<br>|
| Placebo Comparator: Placebo<br>Placebo to Match Q2W s.c. | Drug: Placebo<br>* Placebo will be used to control for normal variability in disease severity.<br>|
| Experimental: Open Label QGE031<br>Open Label QGE031 Q2W s.c. | Drug: QGE031<br>* QGE031 will be evaluated at various dose levels and regimens, based on the impact on disease of the next highest dose level and regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients That Had a Clinical Global Assessment of Change (CGA-C) Responder Rate by Week 12 | Clinical Global Assessment of Change (CGA-C) responder rate was the responder rate at 12 weeks based on the CGA-C in bullous pemphigoid (BP). A patient with a CGA-C score of 3 or 4 indicating 'at least marked improvement from baseline' at 12 weeks was considered a responder. The CGA-C is an investigator assessment of change from baseline and is scored as follows: -4 = Very marked worsening (100% worsening); -3 = Marked worsening (67-99% worsening); -2 = Moderate worsening (34-66% worsening); -1 = Slight worsening (1-33% worsening); 1= Slight improvement (1-33% improvement); 2 = Moderate improvement (34-66% improvement); 3 = Marked improvement (67-99% improvement); 4 = Complete clearance (100% improvement) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Based on Clinical Global Assessment of Change CGA-C Score at 6 Weeks | Clinical Global Assessment of Change (CGA-C) responder rate was the responder rate at 6 weeks based on the CGA-C score in bullous pemphigoid (BP). A patient with a CGA-C score of 3 or 4 indicating marked improvement from baseline at 6 weeks was considered a responder. The CGA-C is an investigator assessment of change from baseline and is scored as follows: -4 = Very marked worsening (100% worsening); -3 = Marked worsening (67-99% worsening); -2 = Moderate worsening (34-66% worsening); -1 = Slight worsening (1-33% worsening); 1= Slight improvement (1-33% improvement); 2 = Moderate improvement (34-66% improvement); 3 = Marked improvement (67-99% improvement); 4 = Complete clearance (100% improvement) | 6 weeks | 
| Number of Patients Investigator Global Assessment Score Over 12 Weeks | Investigator's Global Assessment (IGA) - (scale of 0 to 4, where 0=clear, 1=almost clear, 2=mild, 3=moderate and 4=severe) | Baseline (week 0), week 6 and week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bullous pemphigoid, QGE031