Therapeutic Effect of Hydroxychloroquine on Immunoglobulin A (IgA) Nephropathy Course QUIgAN Study

IgA Nephropathy Clinical Trial

— QUIgAN  

Official title:

Therapeutic Effect of Hydroxychloroquine on Immunoglobulin A (IgA)Nephropathy Course QUIgAN Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06350630
• Other study ID #: 20PH284
• Secondary ID: 2024-512653-25-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: December 31, 2030

Study information

• Verified date: May 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 334
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Social security affiliation

• Signed informed consent

• With biopsy proven IgA nephropathy (any vintage)

• With urine albumin/creatinine > 300mg/g,

• under maximal tolerated labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors for at least 3 months

• With at least one Oxford lesion (M, E, S, T, C) on last available kidney biopsy

• With estimate GFR above 15 mL/min/1,73m² (Chronic Kidney Disease - EPIdemiology collaboration CKD-EPI formula)

• With at least one contraceptive method for women of childbearing age

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Drug:
• Hydroxychloroquine Oral Tablet
Active hydroxychloroquine once daily by oral route at 6.5 mg/kg of ideal weight/day, with maximal dose of 400mg/day for 3 years
• Placebo oral tablet
placebo once daily by oral route (no active drug - same dosage as hydroxychloroquine )

Locations

Country	Name	City	State
France	CHU Gabriel Montpied	Clermont-Ferrand
France	Hospices Civils de Lyon	Lyon
France	AP-HM Hôpital de la Conception	Marseille
France	APHP Hôpital Bichat	Paris
France	APHP Hôpital de Tenon	Paris
France	CHU Lyon Sud	Pierre-Bénite
France	CHU de Saint-Etienne	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute difference in estimate Glomerular Filtration Rate (GFR) between hydroxychloroquine group and control group evolution		3 years
Secondary	nephrological follow-up: proteinuria		1 year
Secondary	nephrological follow-up: albuminuria		1 year
Secondary	nephrological follow-up: GFR		1 year
Secondary	nephrological follow-up: hematuria		1 year
Secondary	nephrological follow-up: systolic and diastolic blood pressure		1 year
Secondary	nephrological follow-up: proteinuria		2 years
Secondary	nephrological follow-up: albuminuria		2 years
Secondary	nephrological follow-up: GFR		2 years
Secondary	nephrological follow-up: hematuria		2 years
Secondary	nephrological follow-up: systolic and diastolic blood pressure		2 years
Secondary	nephrological follow-up: proteinuria		3 years
Secondary	nephrological follow-up: albuminuria		3 years
Secondary	nephrological follow-up: hematuria		3 years
Secondary	nephrological follow-up: systolic and diastolic blood pressure		3 years
Secondary	end stage renal disease (GFR< 15mL/min/1.73m²)		3 years
Secondary	death		3 years
Secondary	adverse events (pruritus, gastro-intestinal disorders) and serious adverse events (QT enlargement, cardiomyopathy, ophthalmologic disorders, neuromyopathy, cytopenia)		3 years