The term ANCA-associated vasculitis (AAV) describes a subset of primary small vessel vasculitides characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA): Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA). AAV are serious multisystem autoimmune disorders that can affect any organ in the body and commonly involve the ear-nose-throat, lungs, kidneys, eyes and joints MedDRA version: 20.0 Level: SOC
Conditions
Interventions
Trade Name: Plaquenil - Hydroxychloroquine 200mg Film coated tablets
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral us
Sponsors
Guy's and St. Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are at least 18 years of age at screening. 2. Have a clinical diagnosis of Granulomatosis Polyangiitis (GPA) or a diagnosis of Microscopic Polyangiitis (MPA) or a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA) according to the Chapel Hill criteria (Appendix 1). 3. Have a Birmingham Vasculitis Activity Score >3 BVAS v.3 (Appendix 2) with minor BVAS items only (no major BVAS items) and be receiving maintenance therapy at a stable dose for 4 weeks prior to randomisation. BVAS should be > 3 at screening and at randomisation. 4. Patients receiving corticosteroids for reasons other than vasculitis must be on a stable regimen for four weeks prior to randomisation. 5. A female patient is eligible to enter the study if she is: • Not pregnant or nursing • Of non-childbearing potential (i.e., women who have had a hysterectomy, are postmenopausal, defined as =1 year without menses, have both ovaries surgically removed or have documented tubal ligation or other permanent sterilization procedure); or • Of childbearing potential. These women must have a negative urine pregnancy test at screening and at baseline and be using at least one effective method of contraception. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Consistent and correct use of one of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent: o Oral contraceptive, either combined or progestogen alone o Injectable progestogen o Implants of levonorgestrel or etonogestrel o Estrogenic vaginal ring o Percutaneous contraceptive patches o Intrauterine device (IUD) or intrauterine system (IUS) with =65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine. 2. Patients with eGFR 470 msec for female > 450 msec for male patients demonstrated by at least two ECGs. 17. Participation in any other interventional trial within the last 6 months. 18. Have a current symptomatic COVID-19 infection. 19. Have been admitted to the ICU in the past 6 months due to a COVID-19 infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate if adjunctive hydroxychloroquine is ranked superior to placebo in controlling active disease. ;Secondary Objective: To investigate if adjunctive hydroxychloroquine reduces the cumulative prednisolone dosage, vasculitis related damage, adverse events, ANCA titres and improves quality of life. ;Primary end point(s): The primary endpoint will be the percentage of patients with • uncontrolled AAV disease activity (defined as BVAS>3) OR • controlled AAV disease activity (BVAS =3) but prednisolone dose for AAV> 7.5mg daily OR • controlled AAV disease activity (BVAS =3) but any corticosteroid use > 7.5mg daily for any reason at any point during the final 12 weeks of the study (±7 days). Inhaled corticosteroids will not contribute to the primary endpoint, nor will methylprednisolone given for rituximab maintenance therapy. BVAS will be scored every 4 weeks during the final 12 weeks (±7 days). The assessment of BVAS in the final 12 weeks (±7 days) will come from the week 44, 48, and 52 visits, at each of which BVAS will be assessed for the previous 4 weeks. ;Timepoint(s) of evaluation of this end point: during the final 12 weeks (+-7 days) of the study. BVAS will be scored every 4 weeks during the final 12 weeks (±7 days). The assessment of BVAS in the final 12 weeks (±7 days) will come from the week 44, 48, and 52 visits, at each of which BVAS will be assessed for the previous 4 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes will evaluate: • Cumulative number of visits where BVAS = 0 (excluding screening, baseline and week 56) • Proportion of patients with treatment failure at week 52 • Cumulative prednisolone dosage • Total number of adverse events • Total number of infections per patient • Total number of vasculitis flares (major and minor) per patient excluding screening, baseline and week 56 • Time to remission • Time to first severe flare • Time to first limited flare • Proportion of patients categorized as having a severe flare at each of the time points in the trial schedule (section 5.4) excluding screening, baseline and week 56 • Proportion of patients categorized as having a limited flare at each of the time points in the trial schedule (section 5.4) excluding screening, baseline and week 56 • Absolute values and relative change from baseline in the Vasculitis Damage Index (VDI) at each time point outlined in the trial schedule (section 5.4). Exploratory outcomes will evaluate: • Incidence of new diabetes mellitus • Prevalence of dyslipidaemia • Fatigue (FACIT score) • Quality of life (SF-36, EQ5D, HAQ, AAV PRO (patient reported outcome) forms) • Glucocorticoid toxicity index • Physician’s Global Assessment (PGA) as per trial schedule 5.4 • ANCA titres as per trial schedule 5.4 • Proportion of patients with medicine compliance of =80% (see section 8.10) • Absolute values and relative change from baseline in the renal variables: serum creatinine, serum albumin, urine protein: creatinine ratio at each time point outlined in the trial schedule (section 5.4). ;Timepoint(s) of evaluation of this end point: Throughout the trial | — |
Countries
United Kingdom
Contacts
Public ContactProf David D'Cruz
Guy's and St Thomas' NHS Foundation Trust
Outcome results
None listed