Clinical trial NCT04128176: 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
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Bullous Pemphigoid
Keywords: Omalizumab
Rituximab
Bullous Pemphigoid
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2019-10-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease Remission
timeFrame: 24 weeks
Secondary outcomes:
measure: Disease Remission
timeFrame: 52 weeks
measure: Number of Disease Flares
timeFrame: 52 weeks
measure: Time to Remission
timeFrame: 52 weeks
measure: Time to Flares
timeFrame: 52 weeks
measure: Duration of Remission
timeFrame: 52 weeks
measure: Clinical Impression
timeFrame: 52 weeks
measure: Patient Impression
timeFrame: 52 weeks
measure: Improvement in Itch
timeFrame: 52 weeks
measure: Health-Related Quality of Life
timeFrame: 52 weeks
Other outcomes:
measure: Adverse Events That Are Related to Treatment
timeFrame: 52 weeks
measure: Gene Expression
timeFrame: 52 weeks
measure: Cumulative Corticosteroid Application
timeFrame: 52 weeks
Locations:
city: Sacramento
country: United States
facility: University of California, Davis, Department of Dermatology
state: California
Study officials:
affiliation: UC Davis
name: Emanual Maverakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.