Hydroxychloroquine in ANCA vasculitis

Phase 1

Conditions: 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: 20.0Level: SOCClassification code 10021428Term: Immune system disordersSystem Organ Class: 10021428 - Immune system disorders
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2018-001268-40-GB

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

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 76

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:
oOral contraceptive, either combined or progestogen alone
oInjectable progestogen
oImplants of levonorgestrel or etonogestrel
oEstrogenic vaginal ring
oPercutaneous contraceptive patches
oIntrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label
6. No contraindications to hydroxychloroquine therapy and normal baseline visual fields at screening.
7. Willing and able to give written informed consent to participate in the trial.
8. Patients should have sufficient English in order to provide informed consent and complete the patient questionnaires.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 76

Exclusion Criteria

1. Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine.
2. Patients with 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:
•Tumour necrosis factor inhibitor treatment (e.g. etanercept)
•Cyclophosphamide
•Abatacept
•Alemtuzumab
•Any experimental or biological therapies
•Intravenous, intramuscular or sub-cutaneous immunoglobin
•Plasma exchange
•Antithymocyte globulin
•Tamoxifen
•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 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. A urine drug screen should be performed and confirmed negative prior to study entry.
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) > 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.

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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