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

NCT06350630 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 20PH2842024-512653-25-00
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 7

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

Keywords

Hydroxychloroquine; proteinuria

Outcome Measures

Primary Outcomes (1)

• Absolute difference in estimate Glomerular Filtration Rate (GFR) between hydroxychloroquine group and control group evolution

  3 years

Secondary Outcomes (17)

• nephrological follow-up: proteinuria

  1 year

• nephrological follow-up: albuminuria

  1 year

• nephrological follow-up: GFR

  1 year

• nephrological follow-up: hematuria

  1 year

• nephrological follow-up: systolic and diastolic blood pressure

  1 year

Study Arms (2)

Hydroxychloroquine

EXPERIMENTAL

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

Drug: Hydroxychloroquine Oral Tablet

Placebo

PLACEBO COMPARATOR

Drug: Placebo oral tablet

Interventions

Hydroxychloroquine Oral Tablet 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

Hydroxychloroquine

Placebo oral tablet DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Ministry of Health, France: collaborator

Study Sites (7)

CHU Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Hospices Civils de Lyon

Lyon, 69437, France

Location

AP-HM Hôpital de la Conception

Marseille, 13385, France

Location

APHP Hôpital Bichat

Paris, 75018, France

Location

APHP Hôpital de Tenon

Paris, 75020, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Glomerulonephritis, IGA; Proteinuria

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double blind trial randomized

Study Record Dates

• First Submitted: March 28, 2024
• First Posted: April 5, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

FR (7)