Hydroxychloroquine in ANCA Vasculitis Evaluation

NCT04316494 | Terminated Phase 4 DMC

• 2 other identifiers: 2519872018-001268-40
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 18

Brief Summary

The purpose of this study is to find out whether hydroxychloroquine, in addition to background treatments, reduces disease activity in patients with Anti-Neutrophilic Cytoplasmic Autoantibodies (ANCA) Vasculitis, a group of autoimmune diseases. Hydroxychloroquine and is an established, effective, safe and inexpensive therapy, widely used in other autoimmune diseases such as lupus and rheumatoid arthritis. The study is open to adults diagnosed with certain types of vasculitis, called Granulomatosis Polyangiitis (GPA), Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA). Participants will be eligible if they are treated with background medication to control their vasculitis disease and have a low level of disease activity as defined by a Birmingham Vasculitis Activity Score (BVAS) of greater than 3. Participants will be randomly placed in 1 of 2 groups. Both groups will be given background medication. One group will receive hydroxychloroquine and the other will receive placebo. Participants will be on treatment for 1 year. 76 ANCA Vasculitis participants will be recruited (38 in each treatment arm) from UK vasculitis specialist centres.

Conditions

Microscopic Polyangiitis; ANCA Associated Vasculitis; Churg-Strauss Syndrome; Wegener Granulomatosis

Keywords

Granulomatosis Polyangiitis; Eosinophilic Granulomatosis with Polyangiitis

Outcome Measures

Primary Outcomes (1)

• The percentage of patients with • uncontrolled AAV disease activity OR • controlled AAV disease activity but prednisolone dose >7.5mg daily OR • controlled AAV disease activity but any corticosteroid use >7.5mg daily for any reason

  The primary endpoint will be the percentage of patients with: EITHER * uncontrolled AAV disease activity (defined as BVAS \> 3) OR * controlled AAV disease activity (BVAS ≤ 3) but prednisolone dose \>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 (±7 days) of the study. Inhaled corticosteroids will not contribute to the primary endpoint, nor will methylprednisolone given for rituximab maintenance therapy.

  BVAS will be assessed during the final 12 (±7 days) weeks that the patient is on the study drug in the trial.

Secondary Outcomes (12)

• Cumulative number of visits BVAS = 0

  Week 4 through to week 52

• Proportion of patients with treatment failure at week 52

  Week 52

• Cumulative prednisolone dosage

  From date of randomisation through to week 56 follow up

• Total number of adverse events

  From date of randomisation through to week 56 follow up

• Total number of infections per patient

  From date of randomisation through to week 56 follow up

Study Arms (2)

Hydroxychloroquine

EXPERIMENTAL

Patients will receive 400mg of Hydroxychloroquine (2 x 200mg) to take daily for 52 weeks. Hydroxychloroquine will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg. Patients weighing \<50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

Patients will receive 400mg of Placebo (2 x 200mg) to take daily for 52 weeks. Placebo will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg. Patients weighing \<50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.

Drug: Placebo

Interventions

Hydroxychloroquine DRUG

White, round, film-coated tablets marked 'HCQ' on one side and 200' on the other side. Excipients: Lactose monohydrate Maize Starch Magnesium Stearate Polyvidone Opadry OY-L-28900

Also known as: Plaquenil

Hydroxychloroquine

Placebo DRUG

Placebo to match Hydroxychloroquine. Excipients: Microcrystalline cellulose Lactose Magnesium Stearate

Also known as: Control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are at least 18 years of age at screening.
• 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.
• Have a Birmingham Vasculitis Activity Score \>3 BVAS v.3 (Appendix 2) with minor BVAS items only (no major BVAS items).BVAS should be \>3 at screening and at randomisation.
• Patients should be receiving maintenance therapy at a stable dose for 4 weeks prior to randomisation. Maintenance therapy is defined as prednisolone and/or azathioprine, methotrexate, mycophenolate, co-trimoxazole or maintenance rituximab therapy.
• Patients receiving corticosteroids for reasons other than vasculitis must be on a stable regimen for four weeks prior to randomisation.
• 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 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:
• Oral contraceptive, either combined or progestogen alone Injectable progestogen Implants of levonorgestrel or etonogestrel Estrogenic vaginal ring Percutaneous contraceptive patches Intrauterine device (IUD) or intrauterine system (IUS) with \<1% failure rate as stated in the product label
• No contraindications to hydroxychloroquine therapy.
• Willing and able to give written informed consent to participate in the trial.
• Patients should have sufficient English in order to provide informed consent and complete the patient questionnaires.

You may not qualify if:

• Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine.
• Patients with an estimated glomerular filtration rate (eGFR) \<30 ml/min.
• Patients weighing \<40kg.
• Sensitivity, anaphylaxis or allergy to hydroxychloroquine or any other 4-aminoquinoline compound.
• Known glucose 6 phosphate dehydrogenase deficiency.
• Known lactose intolerance.
• Evidence of plaque psoriasis.
• Concomitant use of the following medications within the last six months:
• Tumour necrosis factor inhibitor treatment (e.g. etanercept) Cyclophosphamide Abatacept Alemtuzumab Any experimental biological therapies Intravenous, intramuscular or sub-cutaneous immunoglobin Plasma exchange Antithymocyte globulin Tamoxifen Live vaccines
• B cell depleting therapy (rituximab) for remission induction within the last six months. Rituximab maintenance therapy is permitted.
• Severe or rapidly progressive ANCA vasculitis with at least one major BVAS item.
• 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.
• Patients taking long term macrolide antibiotics for a chronic condition. This does not include topical preparations.
• 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.
• 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.

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• Medical Research Council: collaborator

Study Sites (18)

Royal Berkshire NHS Foundation Trust

Reading, Berkshire, RG1 5AN, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

East and North Hertfordshire NHS Trust

Stevenage, Hertfordshire, SG1 4AB, United Kingdom

Location

NHS Highland

Inverness, Inverness-shire, IV2 3JH, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Liverpool University Hospitals NHS Foundation Trust

Liverpool, Merseyside, L9 7AL, United Kingdom

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, Somerset, BA1 3NG, United Kingdom

Location

Surrey and Sussex Healthcare NHS Trust

Redhill, Surrey, RH1 5RH, United Kingdom

Location

University Hospitals Sussex NHS Foundation Trust

Brighton, Sussex, BN2 5BE, United Kingdom

Location

Cardiff & Vale University Health Board

Cardiff, CF14 4XW, United Kingdom

Location

Epsom and St Helier University Hospitals NHS Trust

Epsom, United Kingdom

Location

Cwm Taf Morgannwg University Health Board

Llantrisant, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

South Tyneside and Sunderland NHS Foundation Trust

Sunderland, United Kingdom

Location

Torbay and South Devon NHS Foundation Trust

Torquay, United Kingdom

Location

Related Publications (1)

• Learoyd AE, Arnold L, Reid F, Beckley-Hoelscher N, Casian A, Sangle S, Morton N, Nel L, Cape A, John S, Kim S, Shivapatham D, Luqmani R, Jayne D, Galloway J, Douiri A, D'Cruz D; HAVEN study group. The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation-a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan. Trials. 2023 Apr 6;24(1):261. doi: 10.1186/s13063-023-07108-3.

  PMID: 37024906 DERIVED

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David D'Cruz

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Central trial pharmacist will be unblinded during trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 20, 2020
• Study Start: December 17, 2020
• Primary Completion: May 15, 2025
• Study Completion: May 15, 2025
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (18)