Ixekizumab in the Treatment of Bullous Pemphigoid

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03099538
• Date of registration: 21/03/2017
• Prospective Registration: Yes
• Primary sponsor: Mayo Clinic
• Public title: Ixekizumab in the Treatment of Bullous Pemphigoid
• Scientific title: Ixekizumab in the Treatment of Bullous Pemphigoid
• Date of first enrolment: August 15, 2017
• Target sample size: 4
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03099538
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Aaron Mangold, MD
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Subjects eligible for inclusion in this study have to fulfill all of the following
Inclusion criteria:

- Subjects must be able to understand and comply with the requirements of the study and
communicate with the investigator. Subjects must give written, signed, and dated
informed consent before any study related activity is performed. When appropriate, a
legal representative will sign the informed consent according to local laws and
regulation

- Both men and women must be at least 18 years of age at the time of screening

- Subjects must have clinical, histological, and serological features of BP

- Urticarial plaques and/or vesicles and bullae

- Characteristic eosinophilic spongiosis and/or subepidermal separation of the skin

- Positive direct immunofluorescence (IgG and or C3 at the basement membrane zone) or
indirect immunofluorescence (IgG on the roof of salt- split skin) or positive
serologies on ELISA for BPAG1 or BPAG2

- Subjects must have treatment naive BP or treatment refractory disease, as defined by
failure of at least one established treatment for BP

- Candidate for systemic therapy, defined by

- involvement of greater than 5 percent body surface area or moderate to extensive
disease as defined by: the mean number of new bullae and urticarial plaques that have
appeared over the course of 3 days as determined by the investigator or referring
physician (moderate disease defined by greater than 1 and less than 10 new bullae and
greater than 5 urticarial plaques and extensive disease by greater than 10 new bullae)

- Failure of prior therapy

- Topical treatment

- Systemic immunosuppressant

- Oral antibiotics and/or niacinamide

Exclusion Criteria:

Subjects fulfilling any of the following criteria are not eligible for inclusion in this
study. In order to ensure the recruitment of a representative sample of all eligible
subjects, the investigator may apply no additional exclusions.

- Forms of BP other than classic BP (e.g. mucous membrane BP, Brunsting-Perry BP, p200
BP, p105 BP, or BP with concomitant pemphigus vulgaris Drug-induced BP (e.g., new
onset or current exacerbation from angiotensin converting enzyme inhibitors,
penicillamine, furosemide, phenacetin)

- Subjects who are receiving treatments known to worsen BP and use of penicillamine or
phenacetin and those on angiotensin converting enzyme inhibitors or furosemide who
have not been on a stable dose at least 4 weeks prior to enrollment.

- Ongoing use of prohibited treatments.

- Previous exposure to Ixekizumab or any other biologic drug directly targeting IL-17A
or IL-17 (receptor A)RA

- Use of any other investigational drugs within 5 half-lives of the investigational
treatment before study drug initiation or until the pharmacodynamics effect has
returned to baseline, whichever is longer

- Previous use of IL-20 monoclonal antibody

- Pregnant or nursing (lactating) women (pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive human
chorionic gonadotropin (hCG) laboratory test)

- Women of childbearing potential [Post-menopausal or not of child-bearing potential is
defined by: 1 year of natural (spontaneous) amenorrhea or Surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at
least 6 weeks ago. Oophorectomy alone must confirmed by follow up hormone level
assessment to be considered not of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are using basic methods of
contraception which includes:

- Total abstinence (Periodic abstinence and withdrawal are not acceptable methods of
contraception)

- Female sterilization (bilateral oophorectomy with or without hysterectomy), total
hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
Oophorectomy alone requires follow up hormone level assessment for fertility.

- Male sterilization (at least 6 months prior to screening). The vasectomized male
partner should be the sole partner for that subject.

- Barrier methods of contraception: condom or occlusive cap. Use of oral, injected or
implanted hormonal methods of contraception or other forms or hormonal contraception
that have complete efficacy (failure less than 1 percent). (The dose of the
contraceptive should be stable for 3 months)

- Active ongoing inflammatory diseases of the skin other than BP that might confound the
evaluation of the benefit of Ixekizumab

- Underlying condition (including, but not limited to metabolic, hematologic, renal,
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal
conditions) which, in the opinion of the investigator, significantly immunocompromises
the subject and/or places the subject at unacceptable risk for receiving an
immunomodulatory therapy Investigator discretion should be used for subjects with
pre-existing or recent-onset central or peripheral nervous system demyelinating
disorders Significant medical problems, including but not limited to the following:
uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA)
status of class III or IV)

- Serum creatinine level exceeding 2.0 mg per dL (176.8 micro mol per L) at screening

- Total white blood cell (WBC) count less than 2,500 per microL, platelets less than
100,000 per microL, neutrophils less1500/microL or hemoglobin less than 8.5 g per dL,
at screening

- Active systemic infections during the 2 weeks prior to randomization (common cold
viruses not included) or any infection that reoccurs on a regular basis.

- Investigator discretion should be used regarding subjects who have traveled or resided
in areas of endemic mycoses, such as histoplasmosis, coccidioidomycosis or
blastomycosis and for subjects with underlying conditions that may predispose them to
infection, such as advanced or inadequately controlled diabetes. Due to its endemic
nature in Arizona, coccidioidomycosis screening is performed at baseline. A history of
a disseminated coccidioidomycosis infection will exclude subjects.

- History of an ongoing, chronic or recurrent infectious disease, or evidence of
tuberculosis infection as defined by a positive or indeterminate QuantiFERON
Tuberculosis (TB)-Gold test (QFT) at screening.

- Subjects with a positive QFT test may participate in t


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pemphigoid

Bullous Pemphigoid

Intervention(s)

Drug: Ixekizumab

Primary Outcome(s)

Cessation of Blister Formation [Time Frame: Up to 12 weeks]

Secondary Outcome(s)

Change in Bullous Pemphigoid Disease Activity Index (BPDAI) [Time Frame: Week 0 and week 12]

Change in Multiplex Cytokine Analysis [Time Frame: week 0, 4, 8, 12]

Decrease in Immunoglobulin G Anti-Bullous Pemphigoid 180 and 230 Antibody (Anti-BP180 & 230 IgG) [Time Frame: week 0, 4, 8, 12]

Number of Participants With Treatment-related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). [Time Frame: weeks 0 to 18]

Decrease in Neutrophil and Eosinophil Counts [Time Frame: week 0, 4, 8, 12]

Prednisone Dose (mg) [Time Frame: Epoch 1 (washout- up to 4 weeks) Epoch 2 (week 0 to week 12) Epoch 3 (week 12 to week 16)]

Secondary ID(s)

IRB#16-008302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eli Lilly and Company

Results

• Results available: Yes
• Date Posted: 21/05/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03099538