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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: Hydroxychloroquine Oral Tablet; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • CHU Gabriel Montpied
  • Lyon, France, 69437
    • Hospices Civils de Lyon
  • Marseille, France, 13385
    • AP-HM Hôpital de la Conception
    • Contact: Thomas ROBERT, MD; Phone Number: +33 0662426166; Email: thomas.robert@ap-hm.fr
  • Paris, France, 75018
    • APHP Hôpital Bichat
    • Contact: Eric DAUGAS, PU-PH; Phone Number: +33 0140257101; Email: eric.daugas@aphp.fr
  • Paris, France, 75020
    • APHP Hôpital de Tenon
    • Contact: Khalil EL KAROUI, PU-PH; Phone Number: +33 0156016317; Email: khalil.el-karoui@aphp.fr
  • Pierre-Bénite, France, 69495
    • CHU Lyon Sud
    • Contact: Sarah MEZAACHE, MD; Phone Number: +33 0478863712; Email: sarah.mezaache@chu-lyon.fr
  • Saint-Étienne, France, 42055
    • CHU de Saint-Etienne
    • Contact: Nicolas MAILLARD, MD; Phone Number: +33 0477828127; Email: nicolas.maillard@chu-st-etienne.fr
    • Contact: Carine LABRUYERE; Phone Number: +33 0477120469; Email: carine.labruyere@chu-st-etienne.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo oral tablet; placebo once daily by oral route (no active drug - same dosage as hydroxychloroquine )
Experimental: Hydroxychloroquine; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute difference in estimate Glomerular Filtration Rate (GFR) between hydroxychloroquine group and control group evolution	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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
nephrological follow-up: proteinuria	2 years
nephrological follow-up: albuminuria	2 years
nephrological follow-up: GFR	2 years
nephrological follow-up: hematuria	2 years
nephrological follow-up: systolic and diastolic blood pressure	2 years
nephrological follow-up: proteinuria	3 years
nephrological follow-up: albuminuria	3 years
nephrological follow-up: hematuria	3 years
nephrological follow-up: systolic and diastolic blood pressure	3 years
end stage renal disease (GFR< 15mL/min/1.73m²)	3 years
death	3 years
adverse events (pruritus, gastro-intestinal disorders) and serious adverse events (QT enlargement, cardiomyopathy, ophthalmologic disorders, neuromyopathy, cytopenia)	3 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: proteinuria; Hydroxychloroquine
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 20PH284; 2024-512653-25-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No