Bullous PemphigoidPhase 2NCT03099538
Ixekizumab in the Treatment of Bullous Pemphigoid
A Phase 2 study testing Ixekizumab in people with Bullous Pemphigoid and Pemphigoid, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bullous Pemphigoid, Pemphigoid
- What is being tested?
- Ixekizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2017to 6 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 31Show fewer
- 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 the study if a full tuberculosis work up (according to local practice/guidelines) is completed within 12 weeks prior to establishes conclusively that the subject has no evidence of active tuberculosis.
- If the presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to local country guidelines for at least 4 weeks prior to randomization.
- Past medical history of, or current infection with, human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to new diagnosis at screening
- History of lymphoproliferative disease and or any known malignancy and/or history of malignancy of any organ system within the past 5 years
- Exceptions include:
- For skin squamous cell carcinoma in situ and or well differentiate squamous cell carcinoma and/or basal cell carcinoma and or actinic keratosis and/or melanoma in situ that have been treated with no evidence of recurrence For the cervix carcinoma that has been removed For the colon non-invasive malignant colon polyps that have been removed
- Current severe progressive or uncontrolled disease which the investigator renders the subject unsuitable for the trial or puts the subject at increased risk Inability or unwillingness to undergo repeated venipuncture
- Any medical or psychiatric condition which, in the investigator's opinion, would keep the subject from adhering to the protocol or completing the study per protocol
- History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to the initiation of therapy
- Plans for administration of live vaccines during the study period or in the 12 weeks prior to the initiation of therapy
- Bacillus Calmette-Guerin (BCG) vaccination within 12 months of starting the study or with 12 months after completing the study
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
BP is the most common auto-immune blistering disease of the skin and causes significant morbidity. BP disproportionally affects the elderly population and the current, non-specific immunosuppressive therapies, in addition to patient comorbidities, are associated with a high risk of infection related mortality. Neutrophils and their proteases have been shown to play a major role in the cleavage of Bullous Pemphigoid 180 Antigen (BP180) in BP. Mast cells and other cellular mediators also contribute to the pro-inflammatory environment within and surrounding blisters of BP. However, the prior targeting of mast cells and basophils has resulted in unpredictable disease control. Recently, IL-17 has been identified as a key driver of chronic inflammation in BP. With the increasing aged population in the United States, BP will increase in prevalence and the development of a more targeted approach will be necessary to decrease morbidity and mortality. IL-17 inhibition with Ixekizumab may have targeted, disease-modifying effects on BP. The primary objective is to test the effect of Ixekizumab in the treatment of the autoimmune blistering disease, BP.
- Conditions
- Bullous Pemphigoid, Pemphigoid
- Being tested
- Ixekizumab
- Keywords
- Ixekizumab, Bullous Pemphigoid, Pemphigoid, IL17, IL-17, Interleukin 17
- Medical subject headings
- Pemphigoid, Bullous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxekizumabDrug
Also called Taltz
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Ixekizumab | Experimental | Ixekizumab subcutaneous 160mg week 0, 80mg weeks 2, 4, 6, 8, 10, 12. Receives: Drug: Ixekizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cessation of Blister Formation
Median time to cessation of blister formation during the 12 weeks of therapy.
Measured: Up to 12 weeks
Secondary outcomes (6)
Change in Bullous Pemphigoid Disease Activity Index (BPDAI)
The change in Bullous Pemphigoid Disease Activity Index (BPDAI) from week 0 to 12 of treatment will be measured.The BPDAI is a standard scoring system for cutaneous disease activity and pruritus in BP. BPDAI is predictive of the likelihood of a subsequent flare. The BPDAI consists of scoring various types of lesions and creates a score ranging from 0 to 120. A score of greater than 56 is considered severe disease.
Measured: Week 0 and week 12
Prednisone Dose (mg)
Average daily prednisone dose (mg) will be calculated for each Epoch.
Measured: 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).
The clinical safety of Ixekizumab will be monitored with collection of vital signs, clinical examination, and clinical laboratory studies. Adverse events (AE) will be reported per the Common Terminology Criteria for Adverse Events (CTCAEv4.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE Grade refers to the severity of the AE. The CTCAE displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: weeks 0 to 18
Decrease in Immunoglobulin G Anti-Bullous Pemphigoid 180 and 230 Antibody (Anti-BP180 & 230 IgG)
We will measure the anti-BP180\&230 antibodies through out treatment. These assays will be completed using and ELISA assay. Mayo medical labs references for anti-BP180\&230 (<9.0 Units negative, > or = 9.0 Units positive)
Measured: week 0, 4, 8, 12
Decrease in Neutrophil and Eosinophil Counts
Neutrophil and eosinophil counts will be monitored throughout therapy. Mayo medical labs reports normal neutrophil levels (1.70-7.00X10(9)/L) and normal eosinophil levels (0.05-0.5X10(9)/L)
Measured: week 0, 4, 8, 12
Change in Multiplex Cytokine Analysis
Multiplex cytokine analysis will be performed throughout therapy on Interleukin (IL)- 6, 17, 22, 23, Transforming growth factor beta (TGFb), and matrix-metalloprotease-9 (MMP9).
Measured: week 0, 4, 8, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start15 Aug 2017
- Primary completion6 Jun 2019
- Study completion6 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bullous PemphigoidStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Aaron R. Mangold, Mayo Clinic
- Investigators
- Aaron Mangold, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099538
- Sponsor's protocol ID
- IRB#16-008302
- Status last verified
- May 2020
- First submitted
- 21 Mar 2017
- Last updated
- 21 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ixekizumab in the Treatment of Bullous Pemphigoid
- ClinicalTrials.gov ID
- NCT03099538
- Acronym / sponsor ID
- IRB#16-008302
- Conditions
- Bullous Pemphigoid, Pemphigoid
- Keywords
- Ixekizumab, Bullous Pemphigoid, Pemphigoid, IL17, IL-17, Interleukin 17
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 15 Aug 2017 (actual)
- Primary completion
- 6 Jun 2019 (actual)
- Study completion
- 6 Jun 2019 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 21 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BP is the most common auto-immune blistering disease of the skin and causes significant morbidity. BP disproportionally affects the elderly population and the current, non-specific immunosuppressive therapies, in addition to patient comorbidities, are associated with a high risk of infection related mortality. Neutrophils and their proteases have been shown to play a major role in the cleavage of Bullous Pemphigoid 180 Antigen (BP180) in BP. Mast cells and other cellular mediators also contribute to the pro-inflammatory environment within and surrounding blisters of BP. However, the prior targeting of mast cells and basophils has resulted in unpredictable disease control. Recently, IL-17 has been identified as a key driver of chronic inflammation in BP. With the increasing aged population in the United States, BP will increase in prevalence and the development of a more targeted approach will be necessary to decrease morbidity and mortality. IL-17 inhibition with Ixekizumab may have targeted, disease-modifying effects on BP. The primary objective is to test the effect of Ixekizumab in the treatment of the autoimmune blistering disease, BP.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ixekizumab | Experimental | Drug: IxekizumabIxekizumab subcutaneous 160mg week 0, 80mg weeks 2, 4, 6, 8, 10, 12. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (31 listed)
- 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
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 |
|---|---|---|
| IxekizumabAlso: TaltzSubcutaneous injection | Drug | Ixekizumab |
Primary outcome
Cessation of Blister Formation
Time frame: Up to 12 weeks
Median time to cessation of blister formation during the 12 weeks of therapy.
6 secondary outcomes
Change in Bullous Pemphigoid Disease Activity Index (BPDAI)
Time frame: Week 0 and week 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)
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 Immunoglobulin G Anti-Bullous Pemphigoid 180 and 230 Antibody (Anti-BP180 & 230 IgG)
Time frame: week 0, 4, 8, 12
Decrease in Neutrophil and Eosinophil Counts
Time frame: week 0, 4, 8, 12
Change in Multiplex Cytokine Analysis
Time frame: week 0, 4, 8, 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- 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.
Aaron Mangold, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixekizumab in people with Bullous Pemphigoid and Pemphigoid, run by Mayo Clinic 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 0 inclusion and 31 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: finished, as of the sponsor's last update on 21 May 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cessation of Blister Formation (time frame: Up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 May 2020.