Hydroxychloroquine in ANCA Vasculitis Evaluation (HAVEN)

Phase 4

Conditions: Microscopic polyangiitis
Microscopic polyangiitis, ANCA vasculitis
Musculoskeletal Diseases

Registration Number: ISRCTN79334891

Lead Sponsor: Guy's and St Thomas' NHS Foundation Trust

Brief Summary: 2023 Protocol article in https://pubmed.ncbi.nlm.nih.gov/37024906/ (added 11/04/2023)

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 76

Inclusion Criteria

Patients:
1. Aged =18 years at screening
2. Clinical diagnosis of Granulomatosis Polyangiitis (GPA), Microscopic Polyangiitis (MPA), or Eosinophilic Granulomatosis with Polyangiitis (EGPA) according to the Chapel Hill criteria
3. Birmingham Vasculitis Activity Score (BVAS v.3) >3 with minor BVAS items only (no major BVAS items) at screening and randomisation
4. Receiving maintenance therapy at a stable dose for 4 weeks prior to randomisation
5. If receiving corticosteroids for reasons other than vasculitis must be on a stable regimen for 4 weeks prior to randomisation
6. Not pregnant or nursing. Is either: not of non-childbearing potential, for example, is postmenopausal (1 year without menses), or has had a hysterectomy, bilateral oophorectomy, documented tubal ligation, or other permanent sterilization procedure; or is of childbearing potential and has a negative urine pregnancy test at screening and at baseline and agrees to using an effective method of contraception. Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Partcipants of childbearing potential must consistently and correctly 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:
6.1. Oral contraceptive, either combined or progestogen alone
6.2. Injectable progestogen
6.3. Implants of levonorgestrel or etonogestrel
6.4. Estrogenic vaginal ring
6.5. Percutaneous contraceptive patches
6.6. Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label
7. No contraindications to hydroxychloroquine therapy and normal baseline visual fields at screening
8. Willing and able to give written informed consent to participate in the trial
9. Patients should have sufficient understanding of the English language to provide informed consent and complete the patient questionnaires
10. Negative urine drug screen should be performed prior to study entry

Exclusion Criteria

1. Currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine
2. Estimated Glomerular Filtration Rate (eGFR) <30 ml/min
3. Weighing <40 kg
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:
8.1. Tumour necrosis factor inhibitor treatment (e.g. etanercept)
8.2. Cyclophosphamide
8.3. Abatacept
8.4. Alemtuzumab
8.5. Any experimental or biological therapies
8.6. Intravenous, intramuscular or sub-cutaneous immunoglobin
8.7. Plasma exchange
8.8. Antithymocyte globulin
8.9. Tamoxifen
8.10. Live vaccines
9. B cell depleting therapy (rituximab) for remission induction. Rituximab maintenance therapy is permitted.
10. Severe or rapidly progressive ANCA vasculitis with at least one major Birmingham Vasculitis Activity Score (BVAS) item
11. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases 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 of the study or put the patient at undue risk
12. Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix
13. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to randomisation
14. Have a historically positive test, or test positive at screening,for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody, or are known to be HIV-1 positive
15. Have a Grade 3 or greater laboratory abnormality based on the CTCAE toxicity scale (version 5), unless considered by the investigator to be related to the underlying disease or induction therapy
16. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results, including QT interval corrected using the same consistent formula at each visit (QTc) of >470 msec (female participants) or >450 msec (male participants) demonstrated by at least two ECGs.
17. Participation in any other interventional trial within the last 6 months
18. Current symptomatic COVID-19 infection
19. Have been admitted to the ICU in the past 6 months due to a COVID-19 infection

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Percentage of patients with uncontrolled AAV disease activity measured using Birmingham Vasculitis Activity Score (BVAS), prednisolone dose records, and medication records at 44, 48, 52, and 56 weeks. Uncontrolled AAV is defined as one of the following:<br> 1. BVAS >3)<br> 2. BVAS =3, but prednisolone for AAV >7.5 mg daily<br> 3. BVAS =3, but corticosteroid use for any reason >7.5 mg daily 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.<br>

Secondary Outcome Measures

Name	Time	Method

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