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

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

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.

Study Overview

• Status: Terminated
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Drug: QGE031; Drug: Placebo

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A 1040
    • Novartis Investigative Site
• France
  • Cedex
    • Rouen, Cedex, France, 76031
      • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Freiburg, Germany, 79104
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novartis Investigative Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QGE031; QGE031 240 mg Q2W s.c.	Drug: QGE031; QGE031 will be evaluated at various dose levels and regimens, based on the impact on disease of the next highest dose level and regimen.
Placebo Comparator: Placebo; Placebo to Match Q2W s.c.	Drug: Placebo; Placebo will be used to control for normal variability in disease severity.
Experimental: Open Label QGE031; Open Label QGE031 Q2W s.c.	Drug: QGE031; QGE031 will be evaluated at various dose levels and regimens, based on the impact on disease of the next highest dose level and regimen.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 17, 2012
• First Posted (Estimate): September 20, 2012

Study Record Updates

• Last Update Posted (Estimate): April 28, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: QGE031; bullous pemphigoid
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous
• Other Study ID Numbers: CQGE031X2202