A Phase IIa Open Label Single Arm Study of Safety and Efficacy of rVA576 in Adult Mild to Moderate Bullous Pemphigoid Subjects
- Conditions
- autoimmune blister skin disease10040785
- Registration Number
- NL-OMON46614
- Lead Sponsor
- Akari Therapeutics Plc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Adult male or female *18-year-old patients
2. Subject with newly presenting mild to moderate cutaneous bullous pemphigoid (BP) not on any current systemic corticosteroid or immunomodulator treatment. (Subjects on topical corticosteroids will stop use of these on or before Day1)
3. BPDAI global score at screening of 10-56 (* 10 but <56)
4. Subjects with a relapse of mild to moderate bullous pemphigoid are eligible if their disease was quiescent without any systemic treatment for at least 2 months before the current relapse.
5. Cutaneous bullous pemphigoid (BP) per standard diagnostic criteria:
a. Clinical presentation (cutaneous blistering and/or itchy dermatosis), AND
b. Direct immunofluorescence (DIF) studies performed on perilesional skin collected approximately 1 cm away from a fresh blister, an erosion or papule showing linear (n-serrated) deposition of IgG and/or C3 along the epidermal basement membrane zone, ;AND/OR;Indirect immunofluorescence (IIF) studies performed with patient serum on 1.0M NaCl human salt split skin, showing IgG along the roof of the blister.;6. Karnofsky performance status > 60%
7. Adequate cardiac, renal, hepatic, neurological and psychiatric function as determined by the Investigator and demonstrated by screening laboratory evaluations, vital sign measurement, ECG recording and physical examination results.
8. Women of childbearing potential (WOCBP) must agree to use effective contraception consistently throughout the study 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.
9. Males with a childbearing potential partner must agree to use effective contraception consistently OR have had a vasectomy
10. Willing and able to adhere to the study visit schedule and other protocol requirements including self-injection.
11. Willing and able to provide voluntary written informed consent
12. Willing to receive immunisation against Neisseria meningitidis and antibiotic prophylaxis in accordance with applicable guidelines and local standard of care of the PI at the trial site
Bullous Pemphigoid Exclusion criteria
1. Patients with severe BP. Severe disease to defined as global BPDAI * 56.
2. Patients with refractory BP. Refractory BP may be defined as failure or loss of response to maximal topical or oral steroids.
3. Suspected drug induced BP
4. Concomitant skin conditions preventing physical evaluation of BP.
rVA576 and mometasone related exclusion criteria
5. Participation in a clinical trial of an investigational product within 6 weeks of screening.
6. Known hypersensitivity to tick or to rVA576 and any of its excipients.
7. BP patients on systemic corticosteroid or systemic immunomodulator treatment (including azathioprine, dapsone, rituximab etc.).
8. Treatment with biologics (e.g. etanercept, adalimumab, ustekinumab, infliximab, intravenous immunoglobulin (IVIG) and rituximab or other anti-CD20 therapies) within 5 half-lives of the drugs prior to screening. ;9. Known hypersensitivity to mometasone furoate or to other corticosteroids or to any excipients in mometasone furoate
10. Received rVA576 or other recognised systemic medications for the treatment of the current episode of BP prior to study entry. Prior topical treatment with corticosteroids is permitted. This must be discontinued and study medications started on Day 1
General Exclusion Criteria
11. Patients with severe medical or surgical conditions at screening or Day 1 including, but not limited to cardiac, respiratory, renal, hepatic, haematological, 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.
12. Presence of any malignancy that has been under active treatment or in previous 5 years except for patients with removal of uncomplicated basal cell carcinoma or cutaneous squamous cell carcinoma, who may take part in the study.
13. Congenital or acquired immunodeficiency (e.g. common variable immunodeficiency, organ transplantation).
14. Clinically significant vital sign measurements or ECG findings as determined by the Investigator.
15. Clinically significant abnormal laboratory test results including but not limited to:
* Haemoglobin level <10.0 g/dL
* White blood cell count < 3 x 103/*L
* Lymphocyte count < 0.5 x 103/*L
* Platelet count <100 x 10*9 /L or >1200 x 10*9/L
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN)
* Alkaline phosphatase >3x ULN
* Serum creatinine (S.Cr) >2x ULN
16. Active or recent history of clinically significant infection within 1 month of Screening.
17. Pregnant or breast-feeding, or planning to become pregnant during the study.
18. Evidence of an active disease of hepatitis B (HBsAg positive or HBcAg positive) or hepatitis C (HCV ab positive), CMV (IgM positive) or human immunodeficiency virus (HIV) infection (HIV1/2 Ab positive)
19. Active abuse of alcohol or drugs.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Proportion of participants reporting grade 3, 4 and 5 adverse events, which are<br /><br>related/possibly related to rVA576 during the treatment period.<br /><br><br /><br>The Common Terminology Criteria for Adverse Events (CTCAE v4.03) will be used<br /><br>to grade adverse events by the investigator. At each study visit, participants<br /><br>will be questioned about adverse events they have experienced since the last<br /><br>study visit. </p><br>
- Secondary Outcome Measures
Name Time Method <p>* Mean absolute change in BPDAI activity scores between baseline (Day 1) and<br /><br>Day 42.<br /><br>* Proportion of patients whose BPDAI activity score decreases by 4 or more<br /><br>points between baseline (Day 1) and Day 42.<br /><br>* Proportion of patients whose BPDAI activity score increases by 3 or more<br /><br>points between baseline (Day 1) and Day 42.<br /><br>* Mean absolute change in BPDAI pruritus index between Day 1(baseline) and Day<br /><br>42<br /><br>* Mean change in Dermatology Life Quality Index (DLQI) between baseline (Day 1)<br /><br>and Day 42<br /><br>* Mean change in Treatment of Autoimmune Bullous Disease Quality of Life<br /><br>(TABQOL) between baseline (Day 1) and Day 42</p><br>