Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
Primary Purpose
Bullous Pemphigoid
Status
Not yet recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rituximab combined with Omalizumab
Sponsored by
About this trial
This is an interventional treatment trial for Bullous Pemphigoid focused on measuring Omalizumab, Rituximab, Bullous Pemphigoid
Eligibility Criteria
Inclusion Criteria:
- Patients must be 18-90 years of age
- All individuals must have the ability to provide inform consent
- Patients diagnosed with bullous pemphigoid by biopsy, serum ELISA, direct immunofluorescence, indirect immunofluorescence
- Presence of moderate-to-severe active disease refractory to at least one cycle of rituximab therapy
Exclusion Criteria:
- Diagnosis of mucous membrane pemphigoid or evidence of other non-BP autoimmune blistering disease
- Individuals with allergic reaction or adverse reaction to humanized or murine monoclonal antibodies, or known hypersensitivity to any component of rituximab or omalizumab
- Evidence of acute infection or history of a chronic infection including viral hepatitis, recurrent HSV, AIDS, etc
- Women who are pregnant or actively nursing
- Evidence of any new or uncontrolled concomitant disease that, in the investigator's judgment, would preclude patient participation, including but not limited to cardiovascular, pulmonary, nervous system, renal, hepatic, endocrine, malignant, or gastrointestinal disorders
- Treatment with a live or attenuated vaccine within 28 days prior to first rituximab infusion
Sites / Locations
- University of California, Davis, Department of Dermatology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab combined with Omalizumab
Arm Description
All patients will receive daily doxycycline, nicotinamide, and high-potency topical steroids. Additionally, all patients will receive rituximab combined with omalizumab.
Outcomes
Primary Outcome Measures
Disease Remission
Complete remission is defined as achieving wound healing with no new active lesions (i.e. Bullous Pemphigoid Disease Area Index (BPDAI) score of 0) for at least 2 consecutive weeks during the 24-week treatment period. BPDAI scores can range from 0 to 360, with lower scores indicating less disease activity and better outcomes.
Secondary Outcome Measures
Disease Remission
Proportion of patients achieving a sustained complete remission with rituximab combined with omalizumab at week 52
Number of Disease Flares
Total number of disease flares during the treatment period, as defined by appearance of three or more new lesions a month or at least one large (>10 cm diameter) eczematous lesion or urticarial plaques that do not heal within 1 week or by the extension of established lesions.
Time to Remission
Time to sustained complete remission
Time to Flares
Time to disease flare
Duration of Remission
Duration of sustained complete remission
Clinical Impression
Clinician impression of change in patients' BP symptoms, as measured by the Clinician Global Impression of Change (CGIC) score during the treatment period. The CGIC is a seven point scale to rate the severity of a patient's illness at the time of the assessment, with higher scores indicating better outcomes.
Patient Impression
Patients' impression of change in BP symptoms, as measured by the Patient Global Impression of Change (PGIC) score during the treatment period. The CGIC is a seven point scale to rate the severity of a patient's illness at the time of the assessment, with higher scores indicating better outcomes.
Improvement in Itch
Change in patients' scores in improvement of Itch Numeric Rating Scale (NRS) during the treatment period. The NRS is on a scale of 0 to 10 with 0 representing "no itch" and better outcomes.
Health-Related Quality of Life
Change in health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI) score from baseline to Week 24. The DLQI is a ten item questionnaire with a sum total of 30 points. The higher the score, the more quality of life is impaired, indicating worse outcomes.
Full Information
NCT ID
NCT04128176
First Posted
October 12, 2019
Last Updated
September 1, 2022
Sponsor
University of California, Davis
1. Study Identification
Unique Protocol Identification Number
NCT04128176
Brief Title
Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
Official Title
An Open-Label Study to Evaluate the Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 25, 2023 (Anticipated)
Primary Completion Date
May 25, 2023 (Anticipated)
Study Completion Date
November 25, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the efficacy of rituximab combined with omalizumab in achieving sustained complete remission, evaluated by Bullous Pemphigoid Disease Area Index (BPDAI) in patients with bullous pemphigoid (BP) at Week 24 in patients with active moderate-to-severe BP refractory to rituximab therapy alone.
Detailed Description
This is an open-label, noncontrolled, single center prospective study to evaluate the efficacy and safety of rituximab combined with omalizumab in patients with active moderate-to-severe BP refractory to rituximab treatment alone. Patients must have a confirmed diagnosis of BP and evidence of refractory disease after initiation of rituximab treatment at least 8 weeks prior.
Refractory disease will be defined as a failure of therapy (development of new non-transient lesions or continued extension of old lesions, or failure of established lesions to begin to heal or continued pruritus) or evidence of a relapse/flare (Appearance of ≥3 new lesions/month (blisters, eczematous lesions, or urticarial plaques) or at least one large (>10 cm diameter) eczematous lesion or urticarial plaques that do not heal within 1 week, or extension of established lesions or daily pruritus in patient who have achieved disease control) based on the outcome measures defined for BP from an international panel of experts.41
This study will be conducted at the University of California, Davis Department of Dermatology's investigational site.
The study will consist of 3 periods: a screening period, 24-week treatment period, and a 28-week follow-up period. During the treatment period, patient visits will be monthly. After the primary endpoint at Week 24, follow up assessments will be scheduled every 3 months.
Rituximab 1000 mg will be administered by IV infusion 6 months after the patient's initial cycle of rituximab (received in the screening period). In order to reduce the frequency and severity of infusion-related reactions, all patients will be pre-medicated per the infusion center's therapy beacon protocol. Omalizumab (300 mg) will be administered subcutaneously every 2 weeks starting on Day 1.
All patients will be provided topical clobetasol 0.05% ointment or equivalent strength potency topical corticosteroid. Topical steroid application will be used 40 grams twice daily as needed for itch.
Patients can be discontinued from study treatment at any time during the study. Patients who withdraw from the treatment period will return to the clinic for an early withdrawal visit. After the withdrawal visit, the patient will be asked to enter the follow up period of the study.
From Week 1 through Week 52, patients who do not experience 50% improvement in their BPDAI at week 16 are eligible to receive rescue therapy with prednisone, another immunosuppressive medication (e.g. cellcept), IV Ig, or another treatment or procedure as per the investigator's best medical judgment. Patients who receive rescue therapy will be withdrawn from the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bullous Pemphigoid
Keywords
Omalizumab, Rituximab, Bullous Pemphigoid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rituximab combined with Omalizumab
Arm Type
Experimental
Arm Description
All patients will receive daily doxycycline, nicotinamide, and high-potency topical steroids. Additionally, all patients will receive rituximab combined with omalizumab.
Intervention Type
Drug
Intervention Name(s)
Rituximab combined with Omalizumab
Other Intervention Name(s)
Xolair
Intervention Description
Rituximab 1000 mg will be administered by IV infusion 6 months after the patient's initial cycle of rituximab (received in the screening period).Omalizumab (300 mg) will be administered subcutaneously every 2 weeks starting on Day 1 until week 24 (primary endpoint) and again until week 52 (secondary endpoint).
Primary Outcome Measure Information:
Title
Disease Remission
Description
Complete remission is defined as achieving wound healing with no new active lesions (i.e. Bullous Pemphigoid Disease Area Index (BPDAI) score of 0) for at least 2 consecutive weeks during the 24-week treatment period. BPDAI scores can range from 0 to 360, with lower scores indicating less disease activity and better outcomes.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Disease Remission
Description
Proportion of patients achieving a sustained complete remission with rituximab combined with omalizumab at week 52
Time Frame
52 weeks
Title
Number of Disease Flares
Description
Total number of disease flares during the treatment period, as defined by appearance of three or more new lesions a month or at least one large (>10 cm diameter) eczematous lesion or urticarial plaques that do not heal within 1 week or by the extension of established lesions.
Time Frame
52 weeks
Title
Time to Remission
Description
Time to sustained complete remission
Time Frame
52 weeks
Title
Time to Flares
Description
Time to disease flare
Time Frame
52 weeks
Title
Duration of Remission
Description
Duration of sustained complete remission
Time Frame
52 weeks
Title
Clinical Impression
Description
Clinician impression of change in patients' BP symptoms, as measured by the Clinician Global Impression of Change (CGIC) score during the treatment period. The CGIC is a seven point scale to rate the severity of a patient's illness at the time of the assessment, with higher scores indicating better outcomes.
Time Frame
52 weeks
Title
Patient Impression
Description
Patients' impression of change in BP symptoms, as measured by the Patient Global Impression of Change (PGIC) score during the treatment period. The CGIC is a seven point scale to rate the severity of a patient's illness at the time of the assessment, with higher scores indicating better outcomes.
Time Frame
52 weeks
Title
Improvement in Itch
Description
Change in patients' scores in improvement of Itch Numeric Rating Scale (NRS) during the treatment period. The NRS is on a scale of 0 to 10 with 0 representing "no itch" and better outcomes.
Time Frame
52 weeks
Title
Health-Related Quality of Life
Description
Change in health-related quality of life, as measured by the Dermatology Life Quality Index (DLQI) score from baseline to Week 24. The DLQI is a ten item questionnaire with a sum total of 30 points. The higher the score, the more quality of life is impaired, indicating worse outcomes.
Time Frame
52 weeks
Other Pre-specified Outcome Measures:
Title
Adverse Events That Are Related to Treatment
Description
To evaluate the safety of rituximab combined with omalizumab by monitoring adverse events related to treatment, such as number of abnormal laboratory values.
Time Frame
52 weeks
Title
Gene Expression
Description
To evaluate gene expression profiling of skin biopsies taken (1) before omalizumab therapy and (2) after omalizumab therapy.
Time Frame
52 weeks
Title
Cumulative Corticosteroid Application
Description
To evaluate total cumulative dose of topical corticosteroid applied during treatment and follow up periods
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be 18-90 years of age
All individuals must have the ability to provide inform consent
Patients diagnosed with bullous pemphigoid by biopsy, serum ELISA, direct immunofluorescence, indirect immunofluorescence
Presence of moderate-to-severe active disease refractory to at least one cycle of rituximab therapy
Exclusion Criteria:
Diagnosis of mucous membrane pemphigoid or evidence of other non-BP autoimmune blistering disease
Individuals with allergic reaction or adverse reaction to humanized or murine monoclonal antibodies, or known hypersensitivity to any component of rituximab or omalizumab
Evidence of acute infection or history of a chronic infection including viral hepatitis, recurrent HSV, AIDS, etc
Women who are pregnant or actively nursing
Evidence of any new or uncontrolled concomitant disease that, in the investigator's judgment, would preclude patient participation, including but not limited to cardiovascular, pulmonary, nervous system, renal, hepatic, endocrine, malignant, or gastrointestinal disorders
Treatment with a live or attenuated vaccine within 28 days prior to first rituximab infusion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie T Le, MD
Phone
9167341512
Email
stvle@ucdavis.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Atrin Toussi, BS
Phone
9167341512
Email
amtoussi@ucdavis.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emanual Maverakis, MD
Organizational Affiliation
UC Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Davis, Department of Dermatology
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21605809
Citation
Ujiie H, Nishie W, Shimizu H. Pathogenesis of bullous pemphigoid. Dermatol Clin. 2011 Jul;29(3):439-46, ix. doi: 10.1016/j.det.2011.03.008.
Results Reference
background
PubMed Identifier
30769277
Citation
Maglie R, Hertl M. Pharmacological advances in pemphigoid. Curr Opin Pharmacol. 2019 Jun;46:34-43. doi: 10.1016/j.coph.2018.12.007. Epub 2019 Feb 13.
Results Reference
background
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Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
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