Hydroxychloroquine in ANCA Vasculitis Evaluation

  • STATUS
    Recruiting
  • End date
    Jun 26, 2023
  • participants needed
    76
  • sponsor
    Guy's and St Thomas' NHS Foundation Trust
Updated on 26 January 2021

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 over 2 years.

Description

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 10 sites over 2 years.

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
  • Arrange for optician review

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 three 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.

Details
Condition Autoimmune disease, Autoimmune disease, Wegener's Granulomatosis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis With Polyangiitis, anca-associated vasculitides, anca associated vasculitis
Treatment Placebo, hydroxychloroquine
Clinical Study IdentifierNCT04316494
SponsorGuy's and St Thomas' NHS Foundation Trust
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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) 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
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 and normal baseline
visual fields at screening
\. 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

Exclusion Criteria

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
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
\. B cell depleting therapy (rituximab) for remission induction. 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
\. 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
\. 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
\. 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
\. 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
\. Participation in any other interventional trial within the last 6 months
\. Have a current symptomatic COVID-19 infection
\. Have been admitted to the ICU in the past 6 months due to a COVID-19
infection
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note