E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to Moderate Bullous Pemphigoid |
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E.1.1.1 | Medical condition in easily understood language |
Mild to Moderate Bullous Pemphigoid, an acute or chronic autoimmune skin disease, involving the formation of blisters at the space between the epidermis and dermis skin layers. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006567 |
E.1.2 | Term | Bullous pemphigoid |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to assess the safety of rVA576 in adult subjects with mild to moderate BP. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of rVA576 and its effect on the quality of life of adult subjects with mild to moderate BP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult male or female ≥18 -old patients 2. Subject with newly presenting mild to moderate cutaneous bullous pemphigoid (BP) with or without receiving treatment for the current episode of BP (as indicated in section 5.3). 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 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% (patient with disability can be included at the investigator`s judgement if the score is ≥ 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 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 |
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E.4 | Principal 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 systemic 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 or other treatment for the current BP episode (including azatioprine, dapsone, doxycycline, etc) provided the treatment cannot be discontinued before Day 1 (as indicated in section 5.3) 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 for the treatment of the current episode of BP prior to study entry. Prior topical or systemic treatment with corticosteroids is permitted. This must be discontinued and study medications started on Day 1 (section 5.3)
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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | 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
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |