Hydroxychloroquine in ANCA Vasculitis Evaluation

Inclusion Criteria

1. Are at least 18 years of age at screening.

2. Have a clinical diagnosis of Granulomatosis Polyangiitis (GPA) or a diagnosis ofMicroscopic Polyangiitis (MPA) or a diagnosis of Eosinophilic Granulomatosis withPolyangiitis (EGPA) according to the Chapel Hill criteria.

3. Have a Birmingham Vasculitis Activity Score >3 BVAS v.3 (Appendix 2) with minor BVASitems only (no major BVAS items).BVAS should be >3 at screening and atrandomisation.

4. Patients should be receiving maintenance therapy at a stable dose for 4 weeks priorto randomisation. Maintenance therapy is defined as prednisolone and/orazathioprine, methotrexate, mycophenolate, co-trimoxazole or maintenance rituximabtherapy.

5. Patients receiving corticosteroids for reasons other than vasculitis must be on astable regimen for four weeks prior to randomisation.

6. A female patient is eligible to enter the study if she is: Not pregnant or nursing; OR Of non-childbearing potential (i.e., women who have hada hysterectomy, are postmenopausal defined as ≥1 year without menses, have bothovaries surgically removed or have documented tubal ligation or other permanentsterilization procedure); OR Of childbearing potential. These women must have a negative urine pregnancy test atscreening and at baseline and be using at least one effective method ofcontraception. 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 birthcontrol for 1 month prior to the start of the study agent, during the study, and 16weeks after the last dose of study agent: Oral contraceptive, either combined or progestogen alone Injectable progestogenImplants of levonorgestrel or etonogestrel Estrogenic vaginal ring Percutaneouscontraceptive patches Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label

7. No contraindications to hydroxychloroquine therapy.

8. Willing and able to give written informed consent to participate in the trial.

9. Patients should have sufficient English in order to provide informed consent andcomplete the patient questionnaires.

Exclusion Criteria:

1. Patients currently taking hydroxychloroquine or related antimalarial such asmepacrine or chloroquine.

2. Patients with an estimated glomerular filtration rate (eGFR) <30 ml/min.

3. Patients weighing <40kg.

4. Sensitivity, anaphylaxis or allergy to hydroxychloroquine or any other 4-aminoquinoline compound.

5. Known glucose 6 phosphate dehydrogenase deficiency.

6. Known lactose intolerance.

7. Evidence of plaque psoriasis.

8. Concomitant use of the following medications within the last six months: Tumour necrosis factor inhibitor treatment (e.g. etanercept) CyclophosphamideAbatacept Alemtuzumab Any experimental biological therapies Intravenous,intramuscular or sub-cutaneous immunoglobin Plasma exchange Antithymocyte globulinTamoxifen Live vaccines

9. B cell depleting therapy (rituximab) for remission induction within the last sixmonths. Rituximab maintenance therapy is permitted.

10. Severe or rapidly progressive ANCA vasculitis with at least one major BVAS item.

11. Have clinical evidence of significant unstable or uncontrolled acute or chronicdiseases not due to vasculitis (i.e., cardiovascular, pulmonary, hematologic,gastrointestinal, hepatic, renal, neurological, malignancy or infectious disease)which, in the opinion of the principal investigator, could confound the results ofthe study or put the patient at undue risk.

12. Patients taking long term macrolide antibiotics for a chronic condition. This doesnot include topical preparations.

13. Have a history of malignant neoplasm within the last 5 years, except for adequatelytreated cancers of the skin (basal or squamous cell) or carcinoma in situ of theuterine cervix.

14. Have current drug or alcohol abuse or dependence, or a history of drug or alcoholabuse or dependence within 364 days prior to randomisation. A urine drug screenshould be performed and confirmed negative prior to study entry.

15. Have a historically positive test or test positive at screening for hepatitis Bsurface antigen, hepatitis B core antibody or hepatitis C antibody or are known tobe HIV-1 positive.

16. Have a Grade 3 or greater laboratory abnormality based on the Common TerminologyCriteria for Adverse Events (CTCAE) toxicity scale (version 5), unless considered bythe investigator to be related to the underlying disease or induction therapy.

17. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevantabnormalities that may affect patient safety or interpretation of study results,including: - QT interval corrected using the same consistent formula at each visit (QTc) > 470 msec for female > 450 msec for male patients demonstrated by at leasttwo ECGs.

18. Participation in any other interventional trial within the last 6 months.

19. Have a current symptomatic COVID-19 infection.

20. Have been admitted to the ICU in the past 6 months due to a COVID-19 infection.