Bullous PemphigoidPhase 3NCT04128176
Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
A Phase 3 study testing Rituximab combined with Omalizumab in people with Bullous Pemphigoid, run by University of California, Davis at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Bullous Pemphigoid
- What is being tested?
- Rituximab combined with Omalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2017to 25 Nov 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Davis, Department of Dermatology
Sacramento, California, 95816
About this study
Official title: An Open-Label Study to Evaluate the Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
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.
Read the 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.
- Conditions
- Bullous Pemphigoid
- Being tested
- Rituximab combined with Omalizumab
- Keywords
- Omalizumab, Rituximab, Bullous Pemphigoid
- Medical subject headings
- Pemphigoid, Bullous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab combined with OmalizumabDrug
Also called Xolair
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).
| Study group | Role | What they receive |
|---|---|---|
| Rituximab combined with Omalizumab | Experimental | All patients will receive daily doxycycline, nicotinamide, and high-potency topical steroids. Additionally, all patients will receive rituximab combined with omalizumab. Receives: Drug: Rituximab combined with Omalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (9)
Disease Remission
Proportion of patients achieving a sustained complete remission with rituximab combined with omalizumab at week 52
Measured: 52 weeks
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.
Measured: 52 weeks
Time to Remission
Time to sustained complete remission
Measured: 52 weeks
Time to Flares
Time to disease flare
Measured: 52 weeks
Duration of Remission
Duration of sustained complete remission
Measured: 52 weeks
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.
Measured: 52 weeks
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.
Measured: 52 weeks
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.
Measured: 52 weeks
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.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2019
- Study startMar 2017 (estimated)
- Primary completion25 May 2023 (estimated)
- Study completion25 Nov 2023 (estimated)
Why it stopped: PI did not pursue this study; this study was not IRB-approved and never started.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bullous PemphigoidStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emanual Maverakis, MD, Principal investigator, UC Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04128176
- Sponsor's protocol ID
- 1510820
- Status last verified
- Jul 2024
- First submitted
- 12 Oct 2019
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21605809Maglie 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.
PubMed 30769277
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Efficacy and Safety of Rituximab Combined With Omalizumab in Patients With Bullous Pemphigoid
- ClinicalTrials.gov ID
- NCT04128176
- Acronym / sponsor ID
- 1510820
- Conditions
- Bullous Pemphigoid
- Keywords
- Omalizumab, Rituximab, Bullous Pemphigoid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI did not pursue this study; this study was not IRB-approved and never started.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- Mar 2017 (estimated)
- Primary completion
- 25 May 2023 (estimated)
- Study completion
- 25 Nov 2023 (estimated)
- First posted
- 16 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab combined with Omalizumab | Experimental | Drug: Rituximab combined with OmalizumabAll patients will receive daily doxycycline, nicotinamide, and high-potency topical steroids. Additionally, all patients will receive rituximab combined with omalizumab. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab combined with OmalizumabAlso: XolairRituximab 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). | Drug | Rituximab combined with Omalizumab |
Primary outcome
Disease Remission
Time frame: 24 weeks
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.
9 secondary outcomes
Disease Remission
Time frame: 52 weeks
Number of Disease Flares
Time frame: 52 weeks
Time to Remission
Time frame: 52 weeks
Time to Flares
Time frame: 52 weeks
Duration of Remission
Time frame: 52 weeks
Clinical Impression
Time frame: 52 weeks
Patient Impression
Time frame: 52 weeks
Improvement in Itch
Time frame: 52 weeks
Health-Related Quality of Life
Time frame: 52 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Background: PubMed 21605809Ujiie 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.
- Background: PubMed 30769277Maglie 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emanual Maverakis, MD principal investigator
UC Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab combined with Omalizumab in people with Bullous Pemphigoid, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Remission (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04128176, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.