Evaluation of Safety, Efficacy and Pharmacodynamic Effect of Bertilimumab in Patients With Bullous Pemphigoid

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02226146
• Date of registration: 27/07/2014
• Prospective Registration: Yes
• Primary sponsor: Immune Pharmaceuticals
• Public title: Evaluation of Safety, Efficacy and Pharmacodynamic Effect of Bertilimumab in Patients With Bullous Pemphigoid
• Scientific title: An Open-Label, Proof of Concept Study Designed to Evaluate the Safety, Efficacy and Pharmacodynamic Effect of Bertilimumab in Patients With Newly Diagnosed, Moderate to Extensive Bullous Pemphigoid
• Date of first enrolment: February 2016
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02226146
• 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

Israel, United States

Contacts

• Name: Eli Sprecher, MD
• Affiliation: Sourasky-Ichilov Tel Aviv Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Males or females, = 60 years of age.

2. Karnofsky performance status > 60%

3. Newly diagnosed, Bullous Pemphigoid per standard diagnostic criteria:

- Clinical presentation [2]

- Skin biopsy from a fresh blister showing subepidermal clefting and an
inflammatory infiltrate consisting mainly of eosinophils

- Immunofluorescence (IF) studies performed on uninvolved skin collected
approximately 1 cm away from a fresh blister showing linear deposition of IgG
and/or C3 along the basement membrane zone.

4. Moderate to extensive Bullous Pemphigoid 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 > 1 and = 10 new
bullae daily and = 5 urticarial plaques and extensive disease by >10 new bullae daily)
[3].

5. Adequate cardiac, renal and hepatic function as determined by the Investigator and
demonstrated by screening laboratory evaluations, vital sign measurement, ECG
recording and physical examination results.

6. Females of childbearing potential must agree to use effective contraception
consistently throughout the study (such as hormonal contraception or two forms of
barrier contraception) and have a negative serum pregnancy test at screening and a
negative urine pregnancy test per the schedule of visits. Women are considered
post-menopausal and not of childbearing potential if they have had 12 months of
amenorrhea or have had surgical bilateral oophorectomy (with or without hysterectomy)
or tubal ligation at least six weeks previously.

7. Males must have had a vasectomy or have expressed that they have no interest in
fertility in the future.

8. Fertile males must agree to use effective contraception consistently throughout the
study and for a period of four months following the end of study drug administration.

9. Willing and able to adhere to the study visit schedule and other protocol
requirements.

10. Willing and able to provide voluntary written informed consent or written informed
consent from a legally authorized representative with assent from the patient.

Exclusion criteria:

1. Patients with severe medical or surgical conditions at screening or baseline
including, but not limited to, severe dementia or mental impairment, severe stroke,
severe cardiac insufficiency, severe arterial hypertension, severe or uncontrolled
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac,
neurologic, cerebral, psychiatric, or any other severe acute or chronic medical
condition that may increase the risk associated with study participation/treatment or
may interfere with the interpretation of study results and, in the Investigator's
opinion, would make the patient inappropriate for study entry.

2. Presence of any malignancy that has been under active treatment (e.g., radiotherapy or
chemotherapy) within the 2 years prior to baseline or is anticipated to require
treatment during the study period (including follow up) with the exception of patients
with removal of uncomplicated basal cell carcinoma or cutaneous squamous cell
carcinoma, who may take part in the study.

3. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ
transplantation).

4. Clinically significant vital sign measurements or ECG findings as determined by the
Investigator.

5. Clinically significant abnormal laboratory test results, unless regarded by the
Investigator as related to BP, including but not limited to:

- Hemoglobin level <10.0 g/dL

- White blood cell count < 3 x 103/µL

- Lymphocyte count < 0.5 x 103/µL

- Platelet count <100 x 103/µL or >1200 x 103/µL

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 the upper
limit of normal (ULN)

- Alkaline phosphatase >3 ULN

- Serum creatinine >2 ULN

6. Patients with mild, relapsed or refractory Bullous Pemphigoid. Mild disease defined by
the mean number of new lesions that have appeared over the course of 3 days as
determined by the investigator or referring physician, as follows: = 1 bulla or < 5
urticarial plaques.

7. Concomitant skin conditions preventing physical evaluation of Bullous Pemphigoid.

8. Active or recent history of clinically significant infection within 1 month of
baseline.

9. Pregnant or breast-feeding, or planning to become pregnant during the study.

10. Participation in a clinical trial of an investigational (unapproved) product within 4
weeks of baseline.

11. Known hypersensitivity to bertilimumab or any of the drug excipients.

12. Use of prednisone or other systemic steroids (excluding inhaled or ocular use of
steroids) within 4 weeks prior to baseline. (Concomitant oral corticosteroids
administered as part of the study protocol, from Day 0 onward, are allowed). Use of
class 1 and 2 topical steroids (such as clobetasol propionate cream, reference
Appendix D for further guidance) within 4 weeks prior to baseline. (Use of other
topical steroids is allowed throughout the study at the discretion of the
investigator).

13. Treatment with immunosuppressants (e.g., azathioprine, methotrexate) within 4 weeks
prior to baseline.

14. Treatment with biologics (e.g., etanercept, adalimumab, ustekinumab, infliximab,
intravenous Ig) within 4 months of baseline. Patients who have received rituximab
within 1 year of baseline will be excluded from study participation.

15. Treatment with macrolides or tetracyclines within 4 weeks prior to baseline.

16. Received a vaccine or other immunostimulator within 4 weeks prior to baseline. Subject
has current clinical, radiographic or laboratory evidence of active mycobacterium
tuberculosis (TB) infection or prior evidence of active TB that, in the opinion of the
investigator, has not been adequately treated or controlled and that represents a
reactivation risk. If in the investigator's opinion the patient is at risk for latent
TB, the patient should be evaluated for active/latent TB as applicable (e.g. PPD, QFT,
and/or chest x-ray).

18. Evidence of an active disease of hepatitis B (HBsAg positive or HBcAb positive) or
hepatitis C (HCV ab positive), CMV (IgM positive) or human immunodeficiency virus (HIV)
infection (HIV1/2 Ab positive 19. Active abuse of alcoho


Age minimum: 60 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pemphigoid, Bullous

Intervention(s)

Biological: Bertilimumab

Primary Outcome(s)

Safety Endpoints [Time Frame: Participants will be followed for the duration of the study , an expected average of 118 days]

Secondary Outcome(s)

Efficacy Endpoint: Change in Bullous Pemphigoid Disease Area Index (BPDAI) [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Efficacy Endpoint: Prednisone dose [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Efficacy Endpoint: Change in Autoimmune Bullous Disease Quality of Life (ABQOL) [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Efficacy Endpoint: Change in BPDAI pruritus component [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Efficacy Endpoint: BPDAI responders [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Efficacy Endpoint: Control of disease activity [Time Frame: Participants will be followed for the duration of the study, an expected average of 84 days]

Secondary ID(s)

Immune/BRT/BP-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors