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

NCT ID: NCT06350630

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2030-12-31

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.

Conditions

IgA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hydroxychloroquine

Active hydroxychloroquine once daily by oral route at 6.5 mg/kg of ideal weight/day, with maximal dose of 400/mg day

Group Type: EXPERIMENTAL

Hydroxychloroquine Oral Tablet

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

placebo once daily by oral route (no active drug - same dosage as hydroxychloroquine )

Interventions

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

Intervention Type: DRUG

Placebo oral tablet

placebo once daily by oral route (no active drug - same dosage as hydroxychloroquine )

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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-Etienne, , France

Countries

France

Facility Contacts

Thomas ROBERT, MD

Role: primary

thomas.robert@ap-hm.fr

0662426166 ext. +33

Eric DAUGAS, PU-PH

Role: primary

eric.daugas@aphp.fr

0140257101 ext. +33

Khalil EL KAROUI, PU-PH

Role: primary

khalil.el-karoui@aphp.fr

0156016317 ext. +33

Sarah MEZAACHE, MD

Role: primary

sarah.mezaache@chu-lyon.fr

0478863712 ext. +33

Nicolas MAILLARD, MD

Role: primary

nicolas.maillard@chu-st-etienne.fr

0477828127 ext. +33

Carine LABRUYERE

Role: backup

carine.labruyere@chu-st-etienne.fr

0477120469 ext. +33

Other Identifiers

2024-512653-25-00

Identifier Type: CTIS

Identifier Source: secondary_id

20PH284

Identifier Type: -

Identifier Source: org_study_id