A Clinical study to investigate if rVA576 is safe and has an effect on patients who have mild or moderate Bullous Pemphigoid (a blistering disorder where the skin forms tense blisters)

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-002836-18-NL
• Date of registration: 24/01/2018
• Prospective Registration: Yes
• Primary sponsor: Akari Therapeutics Plc.
• Public title: A Clinical study to investigate if rVA576 is safe and has an effect on patients who have mild or moderate Bullous Pemphigoid (a blistering disorder where the skin forms tense blisters)
• Scientific title: A Phase IIa open label single arm study of safety and efficacy of rVA576 in adult mild to moderate Bullous Pemphigoid subjects
• Date of first enrolment: 07/05/2018
• Target sample size: 9
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002836-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Netherlands

Contacts

• Name: 24 hour medical cover
• Affiliation: Akari Therapeutic Plc

• Name: 24 hour medical cover
• Affiliation: Akari Therapeutic Plc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male or female =18 -old patients
2. Subject with newly presenting mild to moderate 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 BP are eligible if their disease was quiescent without any systemic treatment for at least 2 months before the current relapse.

5. Cutaneous BP per standard diagnostic criteria:
a. Clinical presentation (cutaneous blistering and/or itchy dermatosis),
AND
b. Direct immunofluorescence (DIF) studies performed on erythematous 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, pulmonary, 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. Woman 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 of 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 the applicable guidelines and local standard of care of the PI at the trial site
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
Disease related (BP) Exclusion criteria
1. Patients with severe BP where severe disease is defined as global BPDAI = 56.
2. Patients with refractory BP. Refractory BP may be defined as failure or loss of response to maximal doses of 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 any biologics (e.g. etanercept, adalimumab, ustekinumab, infliximab, intravenous immunoglobulins (IVIG) and rituximab or other anti-CD20 therapies) within its 5 half-lives from screening.
9. Known hypersensitivity to mometasone furoate or to other corticosteroids or to any of the excipients in mometasone furoate
10. Received rVA576 or any 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 baseline 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 with the exception of 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/µL
• Lymphocyte count < 0.5 x 103/µL
• Platelet count <100 x 10*9 /L or >1200 x 10*9/L
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x the upper limit of normal (ULN)
• Alkaline phosphatase >3 x ULN
• Serum creatinine >2 x 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 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 alcohol or drugs.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Mild to Moderate Bullous Pemphigoid
MedDRA version: 21.1 Level: LLT Classification code 10006567 Term: Bullous pemphigoid System Organ Class: 100000004858

Intervention(s)

Product Name: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: rVA576
Current Sponsor code: rVA576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Secondary Objective: To assess the efficacy of rVA576 and its effect on the quality of life of adult subjects with mild to moderate BP.

Timepoint(s) of evaluation of this end point: - Percentage change in BPDAI between baseline (Day1) and Day 42
- Mean absolute change in BPDAI between Day 1(baseline) and Day 42. compared to Day 1
- Proportion of patients whose BPDAI score decreases by 4 or more points between baseline (Day 1) and Day 42.
- Proportion of patients whose BPDAI score increases by 3 or more points between baseline (Day 1) and Day 42.
- Mean change in Dermatology Life Quality Index (DLQI) between baseline (Day 1) and Day 42
-Mean change in Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) baseline (Day 1) and Day 42

Main Objective: The primary objective of the study is to assess the safety of rVA576 in adult subjects with mild to moderate BP.

Primary end point(s): Proportion of participants reporting grade 3, 4 and 5 adverse events, which are related/possibly related to rVA576 during the treatment period.

The Common Terminology Criteria for Adverse Events (CTCAE v4.03) will be used to grade adverse events. At each study visit, participants will be questioned about adverse events they have experienced since the last study visit.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: -Percentage change in BPDAI between baseline (Day1) and Day 42
-Mean absolute change in BPDAI between Day 1(baseline) and Day 42
-Proportion of patients whose BPDAI score decreases by 4 or more points between baseline (Day1) and Day 42.
-Proportion of patients whose BPDAI score increases by 3 or more points between baseline (Day1) and Day 42.

-Mean Change in DLQI between baseline (Day 1) and Day 42
-Mean Change in TABQOL between baseline (Day 1) and Day 42

Secondary end point(s): • Mean absolute change in BPDAI activity scores between Day 1(baseline) and Day 42
• Proportion of patients whose BPDAI activity score decreases by 4 or more points between baseline (Day1) and Day 42.
• Proportion of patients whose BPDAI activity score increases by 3 or more points between baseline (Day1) and Day 42.
• Mean absolute change in BPDAI pruritus index between Day 1 (baseline) and Day 42
• Mean Change in DLQI between baseline (Day 1) and Day 42
• Mean Change in TABQOL between baseline (Day 1) and Day 42

Secondary ID(s)

AK801

Source(s) of Monetary Support

Akari Therapeutics Plc

Ethics review

Status: Approved
Approval date: 07/05/2018
Contact: