Study of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)

NCT04937907 | Completed Phase 2

• 2 other identifiers: 2021SPNR0012019YLYM06
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 2 randomized controlled trial will study the safety, tolerability, and efficacy of Hydroxychloroquine in qualified patients with Alport syndrome. The trial will be open-label, randomized, controlled and will enroll up to 50 patients.

Conditions

Alport Syndrome, X-Linked

Keywords

Alport Syndrome; Hydroxychloroquine; Treatment

Outcome Measures

Primary Outcomes (1)

• Change in urinary erythrocyte count(/HP)

  To assess the change in urinary erythrocyte count(/HP) from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort.

  Baseline to maximum 48 weeks

Secondary Outcomes (6)

• Change in 24-hour urinary protein quantity

  Baseline to maximum 48 weeks

• Change in urinary albumin characterization

  Baseline to maximum 48 weeks

• Change in urinary albumin to creatinine ratio

  Baseline to maximum 48 weeks

• Change in urinary erythrocyte count(urinary sediment analyzer)

  Baseline to maximum 48 weeks

• Change in eGFR from baseline

  Baseline to maximum 48 weeks

Study Arms (2)

Hydroxychloroquine Cohort

EXPERIMENTAL

Patients in the cohort will receive Hydroxychloroquine(HCQ) throughout the study.Patients administered HCQ by oral at a dose of 6.5mg per kilogram twice a day for 6 months. During treatment with HCQ, patients also received enalapril(5-10mg qd).

Drug: Hydroxychloroquine Sulfate 100 milligram (mg) Tab; Drug: Benazepril hydrochloride 10 milligram (mg) Tab

Comparator Cohort

SHAM COMPARATOR

During treatment with HCQ, Patients randomized to Comparator Cohort only received enalapril(5-10mg qd).

Drug: Benazepril hydrochloride 10 milligram (mg) Tab

Interventions

Hydroxychloroquine Sulfate 100 milligram (mg) Tab DRUG

Patients administered HCQ by oral at a dose of 6.5mg per kilogram twice a day at least 6 months.

Also known as: HCQ

Hydroxychloroquine Cohort

Benazepril hydrochloride 10 milligram (mg) Tab DRUG

Patients administered Benazepril by oral at a dose of 5mg or 10mg once a day at least 6 months.

Also known as: Benazepril

Comparator Cohort; Hydroxychloroquine Cohort

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female;
• Age 3-18 years old;
• Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene associated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologic assessment using electron microscopy;
• Screening eGFR ≥ 90 mL/min/1.73 m2;
• ACE inhibitor and/or ARB, the dosing regimen should be stable for at least 4 weeks prior to screening;
• No antirheumatic drugs such as hydroxychloroquine have been used;
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;

You may not qualify if:

• Causes of chronic kidney disease aside from Alport syndrome (including but not limited to other heritable disorders leading to chronic kidney disease, diabetic nephropathy, hypertensive nephropathy, lupus nephritis, IgA nephropathy);
• Prior exposure to hydroxychloroquine;
• Ongoing chronic hemodialysis or peritoneal dialysis therapy;
• Renal transplant recipient;
• Any clinically significant illness within 4 weeks before screening or surgical or medical condition (other than Alport syndrome) that could interfere with the subject's study compliance; confound the study results; impact subject safety; or significantly alter the absorption, distribution, metabolism, or excretion of drugs;
• Participation in other interventional clinical studies;
• Known hypersensitivity to any component of the study drug.

Sponsors & Collaborators

• Shanghai Children's Hospital: lead

Study Sites (1)

Shanghai Children's Hospital

Shanghai, Shanghai Municipality, 200062, China

Location

Related Publications (5)

• Hertz JM, Thomassen M, Storey H, Flinter F. Clinical utility gene card for: Alport syndrome - update 2014. Eur J Hum Genet. 2015 Sep;23(9). doi: 10.1038/ejhg.2014.254. Epub 2014 Nov 12. No abstract available.

  PMID: 25388007 BACKGROUND

• Daga S, Donati F, Capitani K, Croci S, Tita R, Giliberti A, Valentino F, Benetti E, Fallerini C, Niccheri F, Baldassarri M, Mencarelli MA, Frullanti E, Furini S, Conticello SG, Renieri A, Pinto AM. New frontiers to cure Alport syndrome: COL4A3 and COL4A5 gene editing in podocyte-lineage cells. Eur J Hum Genet. 2020 Apr;28(4):480-490. doi: 10.1038/s41431-019-0537-8. Epub 2019 Nov 21.

  PMID: 31754267 BACKGROUND

• Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166. doi: 10.1038/s41584-020-0372-x. Epub 2020 Feb 7.

  PMID: 32034323 BACKGROUND

• Yang YZ, Chen P, Liu LJ, Cai QQ, Shi SF, Chen YQ, Lv JC, Zhang H. Comparison of the effects of hydroxychloroquine and corticosteroid treatment on proteinuria in IgA nephropathy: a case-control study. BMC Nephrol. 2019 Aug 5;20(1):297. doi: 10.1186/s12882-019-1488-6.

  PMID: 31382914 BACKGROUND

• Liu LJ, Yang YZ, Shi SF, Bao YF, Yang C, Zhu SN, Sui GL, Chen YQ, Lv JC, Zhang H. Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. Am J Kidney Dis. 2019 Jul;74(1):15-22. doi: 10.1053/j.ajkd.2019.01.026. Epub 2019 Mar 25.

  PMID: 30922594 BACKGROUND

MeSH Terms

Conditions

Nephritis, Hereditary

Interventions

Tablets; benazepril

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nephritis; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Wen-yan Huang, PhD

  Shanghai Children's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: June 24, 2021
• Study Start: September 8, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)