Bullous Pemphigoid
Conditions
Keywords
bullous pemphigoid, QGE031
Brief summary
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
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)
Interventions
DRUGQGE031
QGE031 will be evaluated at various dose levels and regimens, based on the impact on disease of the next highest dose level and regimen.
DRUGPlacebo
Placebo will be used to control for normal variability in disease severity.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Had a Clinical Global Assessment of Change (CGA-C) Responder Rate by Week 12 | 12 weeks | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Based on Clinical Global Assessment of Change CGA-C Score at 6 Weeks | 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) |
| Number of Patients Investigator Global Assessment Score Over 12 Weeks | Baseline (week 0), week 6 and week 12 | Investigator's Global Assessment (IGA) - (scale of 0 to 4, where 0=clear, 1=almost clear, 2=mild, 3=moderate and 4=severe) |
Countries
Austria, France, Germany, Japan, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QGE031 QGE031 240 mg Q2W s.c. | 13 |
| Placebo Placebo to Match Q2W s.c. | 7 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 1 |
Baseline characteristics
| Characteristic | QGE031 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 14.85 | 67.9 years STANDARD_DEVIATION 14.6 | 65.2 years STANDARD_DEVIATION 14.52 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 13 | 6 / 7 | 2 / 4 | 10 / 11 | 3 / 5 | 2 / 4 |
| serious Total, serious adverse events | 6 / 13 | 2 / 7 | 1 / 4 | 2 / 11 | 0 / 5 | 0 / 4 |
Outcome results
Primary
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)
Time frame: 12 weeks
Population: Pharmacodynamics (PD) analysis set included all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QGE031 | Number of Patients That Had a Clinical Global Assessment of Change (CGA-C) Responder Rate by Week 12 | 8 number of participants |
| Placebo | Number of Patients That Had a Clinical Global Assessment of Change (CGA-C) Responder Rate by Week 12 | 2 number of participants |
Secondary
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)
Time frame: Baseline (week 0), week 6 and week 12
Population: Pharmacodynamics (PD) analysis set included all randomized patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 1 | 4 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 2 | 1 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 0 | 1 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 3 | 4 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 1 | 5 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 3 | 2 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 1 | 0 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 3 | 4 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 2 | 0 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 4 | 9 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 0 | 1 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 4 | 0 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 2 | 4 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12- IGA Score: 4 | 0 Number of participants |
| QGE031 | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 0 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12- IGA Score: 4 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 0 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 0 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 0 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 1 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 1 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 1 | 1 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 2 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 2 | 0 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 2 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 3 | 5 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 3 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 12 - IGA Score: 3 | 1 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 0 - IGA Score: 4 | 2 Number of participants |
| Placebo | Number of Patients Investigator Global Assessment Score Over 12 Weeks | Week 6 - IGA Score: 4 | 0 Number of participants |
Secondary
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)
Time frame: 6 weeks
Population: Pharmacodynamics (PD) analysis set included all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QGE031 | Response Based on Clinical Global Assessment of Change CGA-C Score at 6 Weeks | 8 number of participants |
| Placebo | Response Based on Clinical Global Assessment of Change CGA-C Score at 6 Weeks | 2 number of participants |