Biologics in refractory vasculitis (BIOVAS): A pragmatic, randomised, double-blind, placebo-controlled, modified-crossover trial of biologic therapy for refractory vasculitis in adults and children.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 140

Inclusion Criteria

1. Aged at least 5 years
2. Have given, or their parent/ legal guardian aged = 16 years old has given, written informed consent
3. Diagnosis of NAAV
4. Refractory disease defined by:
- Active disease, BVAS v3 modified for BIOVAS (BVAS v3-BIOVAS)/ PVAS with = 1 severe (new/worse) or =3 non-severe (new/worse) items despite 12 weeks of conventional therapy prior to screening visit (OR)
- Inability to reduce prednisolone below 15mg/day or (0.2mg/kg/day in case of children) without relapse in the 12 weeks prior to screening visit

Are the trial subjects under 18? yes
Number of subjects for this age range: 14
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 91
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

1.Previous treatment failure/contraindication to = 2 active trial IMPs
2.Increase in the dose or frequency of background immunosuppressive (e.g. methotrexate) or anti-cytokine therapy within 30 days of screening visit
3.Use of plasma exchange or intravenous immunoglobulins within 30 days, or cyclophosphamide or lymphocyte depleting biologic (e.g. rituximab) within 6 months of screening visit
4.Have an active systemic bacterial, viral or fungal infection, or active/latent tuberculosis
5.Hepatitis B (HB) core antibody (Ab) or HB surface antigen positive or hepatitis C antibody positive or human immunodeficiency virus (HIV) antibody test positive
6.History of malignancy within five years prior to screening visit or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure
7.Pregnant or breastfeeding
8.Severe disease, which in the opinion of the physician prevents randomisation to placebo
9.Recent or upcoming major surgery within 45 days of screening visit
10.Leukocyte count < 3.5 x 10^9, platelet count < 100 x 10^9 cells/l, neutrophil count of < 1 x 10^9 cells/l
11.ALT or ALP > 3 times the upper limit of normal
12.Symptomatic congestive heart failure (NYHA class III/IV) requiring prescription medication within 90 days of screening visit
13.Demyelinating disorders
14.History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the participant at unacceptable risk because of trial participation
15. Administration of live or live attenuated vaccines within 45 days of screening
16. Participation in any clinical trial of an investigational medicinal product within 30 days prior to screening or within 5 half-lives after taking the last dose
17. Diagnosis of adenosine deaminase type 2 (DADA2)
18. Hypersensitivity to the active IMP substance or to any of the formulation excipients

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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