Clinical trial NCT06350630: Therapeutic Effect of Hydroxychloroquine on Immunoglobulin A (IgA) Nephropathy Course QUIgAN Study
Official title: Therapeutic Effect of Hydroxychloroquine on Immunoglobulin A (IgA)Nephropathy Course QUIgAN Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: IgA Nephropathy
Keywords: Hydroxychloroquine
proteinuria
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2024-04-05
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind trial randomized
Primary purpose: TREATMENT

Brief summary: immunoglobulin A (IgA) nephropathy (Berger disease) is the most frequent primary glomerulonephritis worldwide. This disease accounts for about 5% of the causes of end stage renal disease in France, representing a major public health issue. Its pathophysiology seems to be triggered by mucosal immunity abnormalities leading to the systemic misaddressing of mucosal IgA, generation of circulating immunoglobulin A1 (IgA1) immune complexes finally deposited in renal glomeruli leading to renal tissue inflammation and scarring processes. Among this pathogeny, innate immunity is involved at several steps, including mucosal immunity.

In this regard, hydroxychloroquine has been shown to generate a global anti-inflammatory effect, particularly through its action on Toll like receptors and dendritic cells. This drug is well tolerated, widely used for other auto-immune diseases (e.g. Systemic Lupus Erythematosus) and very low priced.

One randomized controlled study conducted in China has recently shown a significant drop in proteinuria of IgA nephropathy patients treated with hydroxychloroquine (-48.4%) compared to the placebo group (+10.0%), after a quite short-term follow-up (6 months) and a moderate statistical power (30 patients in each group).

Considering (i) the potential mechanism of therapeutic effect on this disease, (ii) the well documented safety profile of the drug for rheumatologic indications and posologies, and its low cost (iii) its efficacy in reducing proteinuria in IgA nephropathy patients in a preliminary Chinese randomized control study, the investigators aim in this study at establishing the beneficial impact of hydroxychloroquine on IgA nephropathy in a double blind randomized controlled trial on a Caucasian French population with harder outcomes and a longer follow-up compared to the Chinese preliminary study.


Eligibility criteria: Inclusion Criteria:

* Social security affiliation
* Signed informed consent
* With biopsy proven IgA nephropathy (any vintage)
* With at least one Oxford lesion (M, E, S, T, C) on last available kidney biopsy - With urine albumin/creatinine \> 300mg/g,
* under maximal tolerated labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors for at least 3 months
* Sodium-Glucose Transport Protein 2 (SGLT-2) inhibitors initiated at least 1 month before inclusion visit
* Only patients treated with SGLT2i and RAAS dual therapy before inclusion
* With estimate GFR above 15 mL/min/1,73m² (Chronic Kidney Disease - EPIdemiology collaboration CKD-EPI formula)
* Woman in childbearing with a highly effective method of contraception
* Agreement of woman in childbearing potential (WOCBP) to perform a urine pregnancy test every month until three months after the end of study treatment
* Agreement of fertile male with WOCBP partner to use a condom for the duration of the study treatment up to 3 months after treatment the end of study treatment.

Exclusion Criteria:

* Secondary IgA nephropathy (Henoch Schonlein purpura, cirrhosis, inflammatory bowel disease)
* Corticosteroid or immunosuppressive therapies in the past year before screening
* Contra-indication to hydroxychloroquine (retinopathy, maculopathy, history of intolerance to hydroxychloroquine...)
* Uncontrolled hypertension (systolic blood pression\> 160 mmHg and/or diastolic blood pression \>110 mmHg )
* Long QT interval and/or QT prolonging medicines
* Pregnancy or lactation

Primary outcomes:
measure: Absolute difference in estimate Glomerular Filtration Rate (GFR) between hydroxychloroquine group and control group evolution
timeFrame: 3 years
Secondary outcomes:
measure: nephrological follow-up: proteinuria
timeFrame: 1 year
measure: nephrological follow-up: albuminuria
timeFrame: 1 year
measure: nephrological follow-up: GFR
timeFrame: 1 year
measure: nephrological follow-up: hematuria
timeFrame: 1 year
measure: nephrological follow-up: systolic and diastolic blood pressure
timeFrame: 1 year
measure: nephrological follow-up: proteinuria
timeFrame: 2 years
measure: nephrological follow-up: albuminuria
timeFrame: 2 years
measure: nephrological follow-up: GFR
timeFrame: 2 years
measure: nephrological follow-up: hematuria
timeFrame: 2 years
measure: nephrological follow-up: systolic and diastolic blood pressure
timeFrame: 2 years
measure: nephrological follow-up: proteinuria
timeFrame: 3 years
measure: nephrological follow-up: albuminuria
timeFrame: 3 years
measure: nephrological follow-up: hematuria
timeFrame: 3 years
measure: nephrological follow-up: systolic and diastolic blood pressure
timeFrame: 3 years
measure: end stage renal disease (GFR< 15mL/min/1.73m²)
timeFrame: 3 years
measure: death
timeFrame: 3 years
measure: adverse events (pruritus, gastro-intestinal disorders) and serious adverse events (QT enlargement, cardiomyopathy, ophthalmologic disorders, neuromyopathy, cytopenia)
timeFrame: 3 years
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: AP-HM Hôpital de la Conception
city: Paris
country: France
facility: APHP Hôpital Bichat
city: Paris
country: France
facility: APHP Hôpital de Tenon
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne
Study officials:
References: