Clinical trial NCT04465292: The Effects of Tildrakizumab in Treatment of Bullous Pemphigoid
Official title: The Effects of Tildrakizumab in Treatment of Bullous Pemphigoid
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Pemphigoid, Bullous
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Joseph Merola
First posted: 2020-07-10
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, pilot study evaluating the efficacy of tildrakizumab on the treatment of bullous pemphigoid (BP) in eligible patients (see detailed study protocol). Three total doses of tildrakizumab 100mg will be administered at Weeks 0, 4, 16 a total of 16 weeks of treatment by the study staff to patients with bullous pemphigoid. The patients will be followed for a total of 24 weeks.

Detailed description: The investigators will recruit 16 patients with bullous pemphigoid 18 years of age and older with confirmed diagnosis of bullous pemphigoid on biopsy (both H\&E and Direct Immunofluorescence (DIF) +/- IIF and ELISA) At the initial screening visit, demographic information will be obtained, inclusion and exclusion criteria, and informed consent obtained for those deemed eligible for enrollment. Three total doses of Tildrakizumab 100mg will be administered at Weeks 0, 4, 16 a total of 16 weeks of treatment by the study staff. Subjects will be evaluated for improvement in primary and secondary endpoints using clinical examination and questionnaires during initial and follow-up visits at screening, Weeks 0, 4, 16, and 24, a total of 24 week followup period.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years of age
2. Diagnosis of diffuse bullous pemphigoid clinically and confirmed on H\&E, DIF +/- IIF/ELISA
3. Able and willing to provide informed consent, participate in study visits, and undergo visit procedures

Exclusion Criteria:

1. Unusual and localized variant of bullous pemphigoid will be excluded, these include but not limited to, BP sine rash, dyshidrosiform pemphigoid, pemphigoid vegetans, pemphigoid nodularis, lichen planus pemphigoid, pretibial BP, vulva BP, peristomal BP, umbilical BP, Brunsting-Perry, BP localized only to sites of injury, radiation, amputation, paralysis, or other underlying dermatosis.
2. Prior tildrakizumab use.
3. Treatment with a systemic immune-regulating nonsteroidal medication(s) within 6 weeks of the baseline visit, or use of systemic steroid within 2 weeks of baseline visit. Examples of systemic immune-regulating nonsteroidal medications include azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, intravenous immunoglobulins, dapsone, colchicine, sulfasalazine, or omalizumab.
4. Treatment with other biologic agents, such as TNF inhibitors, anti-IL17 agents, anti-IL12/23 agents, anti-IL4/13, anti-IL5, anti-IL23 agents or anti-eotaxin, within 4 months of baseline visit.
5. Use of rituximab within at 6 months (or until lymphocyte counts by CD19 and CD20 have normalized if longer than 6 months) of the baseline visit.
6. Concurrent use of any medication that may affect the efficacy of tildrakizumab.
7. Use of belimumab within the past year (given tildrakizumab may enhance the adverse effect of belimumab)
8. Other active conditions, such as psoriasis or contact dermatitis, that may confound clinical evaluations of dermatitis and patient-reported symptoms.
9. Increased risk of infection or reactivated infection, including history of human immunodeficiency virus, hepatitis B, hepatitis C, endoparasitic infections, receipt of a live attenuated vaccine within 3 months of the baseline visit, chronic or acute infection requiring treatment within 4 weeks of the baseline visit, baseline immunodeficiency status otherwise nonspecified (i.e. history of recurrent or resistant infections)
10. History of malignancy excluding local cutaneous squamous cell carcinoma, basal cell carcinoma or cervical carcinoma in situ that has been fully treated.
11. Women who are or plan to become pregnant or breastfeed during study participation or are unable or not willing to use birth control during the study and for 4 months after the last dose of tildrakizumab. Options for birth control include abstinence, double barrier (i.e. male condom and female diaphragm), vasectomy, intrauterine device, and hormonal contraception. Females who have not had menses within 1 year of the baseline, bilateral tubal ligation, hysterectomy, and/or bilateral oophorectomy visit do not require additional methods contraception during study participation.
12. Unstable condition or status, as per study investigator's judgment, that may lead to more likely discontinuation from the study including but not limited to major, recurrent medical illnesses that may require hospital admission and/or discontinuation of tildrakizumab, surgery that would require discontinuation of tildrakizumab and/or major rehabilitation, inability to participate in all study visits.

Primary outcomes:
measure: Change in Disease Severity
timeFrame: Weeks 0, 4, 16, and 24
Secondary outcomes:
measure: Change in Bullous Pemphigoid Disease Activity Index (BPDAI)
timeFrame: Weeks 0, 4, 16, and 24
measure: Change in BPDAI-Pruritus
timeFrame: Weeks 0, 4, 16, and 24
measure: Change in Dermatology Life Quality Index (DLQI)
timeFrame: Weeks 0, 4, 16, and 24
measure: anti-BP180, BP230 IgG
timeFrame: Weeks 0, 4, 16, and 24
measure: Total IgE
timeFrame: Weeks 0, 4, 16, and 24
measure: Cytokine level
timeFrame: Weeks 0, 4, 16, and 24
Other outcomes:
Locations:
Study officials:
References: