Ixekizumab in the Treatment of Bullous Pemphigoid

NCT03099538 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB#16-008302
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, Interleukin (IL)-17 has been identified as a key driver of chronic inflammation in Bullous Pemphigoid (BP). Ixekizumab is a recombinant high-affinity fully human monoclonal antibody that targets IL-17A Immunoglobulin gamma-1 (IgG1)/kappa-class. The purpose of this study is to determine the effect of Ixekizumab on BP patients.

Conditions

Bullous Pemphigoid; Pemphigoid

Keywords

Ixekizumab; Bullous Pemphigoid; Pemphigoid; IL17; IL-17; Interleukin 17

Outcome Measures

Primary Outcomes (1)

• Cessation of Blister Formation

  Median time to cessation of blister formation during the 12 weeks of therapy.

  Up to 12 weeks

Secondary Outcomes (6)

• Change in Bullous Pemphigoid Disease Activity Index (BPDAI)

  Week 0 and week 12

• Prednisone Dose (mg)

  Epoch 1 (washout- up to 4 weeks) Epoch 2 (week 0 to week 12) Epoch 3 (week 12 to week 16)

• Number of Participants With Treatment-related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).

  weeks 0 to 18

• Decrease in Immunoglobulin G Anti-Bullous Pemphigoid 180 and 230 Antibody (Anti-BP180 & 230 IgG)

  week 0, 4, 8, 12

• Decrease in Neutrophil and Eosinophil Counts

  week 0, 4, 8, 12

Study Arms (1)

Ixekizumab

EXPERIMENTAL

Ixekizumab subcutaneous 160mg week 0, 80mg weeks 2, 4, 6, 8, 10, 12.

Drug: Ixekizumab

Interventions

Ixekizumab DRUG

Subcutaneous injection

Also known as: Taltz

Ixekizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Pemphigoid, Bullous

Interventions

ixekizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Aaron R. Mangold, MD
• Organization: Mayo Clinic

mangold.aaron@mayo.edu

480-301-4256

Study Officials

• Aaron Mangold, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Dermatology

Model Details: This is a single center, exploratory, open-label, single-arm design study of 12 patients with BP. Treatment naïve and treatment refractory patients with BP will be treated with Ixekizumab. Patients who are non-responders, to physician choice standard of care, will undergo a washout period and will be enrolled in the study.

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: April 4, 2017
• Study Start: August 15, 2017
• Primary Completion: June 6, 2019
• Study Completion: June 6, 2019
• Last Updated: May 21, 2020
• Results First Posted: May 21, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)