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Hydroxychloroquine in ANCA Vasculitis Evaluation

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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. 3. 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. 4. 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. 5. Patients receiving corticosteroids for reasons other than vasculitis must be on a stable 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 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. 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 and complete the patient questionnaires.

Exclusion Criteria:

1. Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine 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) Cyclophosphamide Abatacept Alemtuzumab Any experimental biological therapies Intravenous, intramuscular or sub-cutaneous immunoglobin Plasma exchange Antithymocyte globulin Tamoxifen Live vaccines. 9. B cell depleting therapy (rituximab) for remission induction within the last six months. 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. Patients taking long term macrolide antibiotics for a chronic condition. This does not include topical preparations. 13. 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. 14. 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. 15. 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. 16. Have a Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale (version 5), unless considered by the investigator to be related to the underlying disease or induction therapy. 17. Screening 12-lead electrocardiogram (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.
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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04316494
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Guy's and St Thomas' NHS Foundation Trust
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

David D'Cruz
Principal Investigator Affiliation Guy's and St Thomas' NHS Foundation Trust
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United Kingdom
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

ANCA Associated Vasculitis, Microscopic Polyangiitis, Churg-Strauss Syndrome, Wegener Granulomatosis
Additional Details

This is a multi-centre, randomised, placebo-controlled, double-blind study to evaluate if hydroxychloroquine in combination with background maintenance therapy improves the clinical response and quality of life in patients with AAV. 76 participants who have Granulomatosis with Polyangiitis, Microscopic Polyangiitis or Eosinophilic Granulomatosis with Polyangiitis will be recruited from 20 sites. They will be randomised in a 1:1 ratio of hydroxychloroquine or placebo. Neither the patient nor the research team will know which treatment group the participant is in. Once the participant agrees to take part and has signed informed consent, they will undergo the following assessments, tests and procedures to find out if they can take part in the study. Some may be routinely done by the study doctor as part of regular vasculitis care even if the participants are not in the study:

  • - Medical history.
  • - Birmingham Vasculitis Activity Score (BVAS) - Physical exam.
  • - Blood tests.
  • - Pregnancy test.
  • - Urine drug test.
  • - Electrocardiogram.
If the patient is eligible to take part in the study, they will be randomised to receive either hydroxychloroquine or placebo in addition to background medication. Participants will receive 2 tablets to take once a day over the course of a year. Participants may have their dose reduced to 1 tablet dependent on their weight at baseline and renal function. All participants will have their prednisolone dose tapered down over the course of the study. Participants will be asked to fill in a patient diary on a weekly basis to record whether they've taken their medication, and if they've experienced any change of symptoms. Participants will be asked to attend the hospital at weeks 4, 16, 28, 40, 44, 48, 52 and 56. At each of these visits, participants will undertake some or all of the following tests/assessments:
  • - Physical exam including visual acuity.
  • - Weight and vital signs.
  • - BVAS assessment and Vasculitis Damage Index (VDI) - Patient questionnaires.
  • - If there are any changes to their medicines and health status.
  • - If they experiencing any side effects.
  • - Blood samples and urine tests to see how the study drug is affecting the body.
  • - At two visits, participants will also be asked to undergo an electrocardiogram (ECG).
Patients will be followed up by phone in weeks 10, 22, and 34. This phone call will be based on the ANCA-associated Vasculitis Patient Reported Outcome (AAV PRO) questionnaire and patients will also be encouraged to report any adverse events. Patients reporting new or worsening symptoms will be invited to the hospital for an unscheduled visit. In addition to clinical bloods, 76ml of blood will be taken for research purposes for all participants. These will be taken at the same time as clinical bloods to minimise discomfort for the participant. Participants at Guy's and St Thomas' will have an additional 200ml of blood taken for isolation of cells. These bloods will be stored and kept for future research, with the written consent of the participant.

Arms & Interventions

Arms

Experimental: Hydroxychloroquine

Patients will be 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.

Placebo Comparator: Placebo

Patients will be 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.

Interventions

Drug: - Hydroxychloroquine

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

Drug: - Placebo

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Royal Berkshire NHS Foundation Trust, Reading, Berkshire, United Kingdom

Status

Recruiting

Address

Royal Berkshire NHS Foundation Trust

Reading, Berkshire, RG1 5AN

Site Contact

Oliver Flossmann, MD

david.d'cruz@kcl.ac.uk

02071889756

Cambridge, Cambridgeshire, United Kingdom

Status

Recruiting

Address

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ

Site Contact

David Jayne, MD

david.d'cruz@kcl.ac.uk

02071889756

East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire, United Kingdom

Status

Recruiting

Address

East and North Hertfordshire NHS Trust

Stevenage, Hertfordshire, SG1 4AB

Site Contact

Gayathri Rajakaruna, MD

david.d'cruz@kcl.ac.uk

02071889756

NHS Highland, Inverness, Inverness-shire, United Kingdom

Status

Recruiting

Address

NHS Highland

Inverness, Inverness-shire, IV2 3JH

Site Contact

Jan Sznajd, MD

david.d'cruz@kcl.ac.uk

02071889756

Leicester, Leicestershire, United Kingdom

Status

Recruiting

Address

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE3 9QP

Site Contact

Chee Kay Cheung, MD

david.d'cruz@kcl.ac.uk

02071889756

Liverpool, Merseyside, United Kingdom

Status

Recruiting

Address

Liverpool University Hospitals NHS Foundation Trust

Liverpool, Merseyside, L9 7AL

Site Contact

Jagdish Nair, MD

david.d'cruz@kcl.ac.uk

02071889756

Bath, Somerset, United Kingdom

Status

Recruiting

Address

Royal United Hospitals Bath NHS Foundation Trust

Bath, Somerset, BA1 3NG

Site Contact

Sarah Tansley, MD

david.d'cruz@kcl.ac.uk

02071889756

Surrey and Sussex Healthcare NHS Trust, Redhill, Surrey, United Kingdom

Status

Recruiting

Address

Surrey and Sussex Healthcare NHS Trust

Redhill, Surrey, RH1 5RH

Site Contact

Raad Makadsi, MD

david.d'cruz@kcl.ac.uk

02071889756

Brighton, Sussex, United Kingdom

Status

Recruiting

Address

University Hospitals Sussex NHS Foundation Trust

Brighton, Sussex, BN2 5BE

Site Contact

Teresa Doherty, MD

david.d'cruz@kcl.ac.uk

02071889756

Cardiff & Vale University Health Board, Cardiff, United Kingdom

Status

Recruiting

Address

Cardiff & Vale University Health Board

Cardiff, , CF14 4XW

Site Contact

Siân Griffin, MD

david.d'cruz@kcl.ac.uk

02071889756

Epsom, United Kingdom

Status

Recruiting

Address

Epsom and St Helier University Hospitals NHS Trust

Epsom, ,

Site Contact

Bhrigu Sood, MD

david.d'cruz@kcl.ac.uk

02071889756

Llantrisant, United Kingdom

Status

Recruiting

Address

Cwm Taf Morgannwg University Health Board

Llantrisant, ,

Site Contact

Ceril Rhys-Dillon, MD

david.d'cruz@kcl.ac.uk

02071889756

London, United Kingdom

Status

Recruiting

Address

Guy's and St Thomas' NHS Foundation Trust

London, , SE1 9RT

Site Contact

Shirish Sangle, MD

david.d'cruz@kcl.ac.uk

02071889756

London, United Kingdom

Status

Recruiting

Address

King's College Hospital NHS Foundation Trust

London, , SE5 9RS

Site Contact

Arti Mahto, MD

david.d'cruz@kcl.ac.uk

02071889756

Imperial College Healthcare NHS Trust, London, United Kingdom

Status

Recruiting

Address

Imperial College Healthcare NHS Trust

London, , W12 0HS

Site Contact

Stephen McAdoo, MD

david.d'cruz@kcl.ac.uk

02071889756

Maidstone and Tunbridge Wells NHS Trust, Maidstone, United Kingdom

Status

Withdrawn

Address

Maidstone and Tunbridge Wells NHS Trust

Maidstone, ,

Oxford, United Kingdom

Status

Recruiting

Address

Oxford University Hospitals NHS Foundation Trust

Oxford, ,

Site Contact

Raashid Luqmani, MD

david.d'cruz@kcl.ac.uk

02071889756

Sunderland, United Kingdom

Status

Recruiting

Address

South Tyneside and Sunderland NHS Foundation Trust

Sunderland, ,

Site Contact

Rebecca Batten, MD

david.d'cruz@kcl.ac.uk

02071889756

Torquay, United Kingdom

Status

Recruiting

Address

Torbay and South Devon NHS Foundation Trust

Torquay, ,

Site Contact

Kirsten Mackay, MD

david.d'cruz@kcl.ac.uk

02071889756