Clinical trial NCT04937907: Study of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)
Official title: Efficacy and Safety of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alport Syndrome, X-Linked
Keywords: Alport Syndrome
Hydroxychloroquine
Treatment
Lead sponsor: Shanghai Children's Hospital
Sponsor class: OTHER
First posted: 2021-06-24
Enrollment: 50
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Patients in the Phase 2 cohort will be randomized 1:1 to either Hydroxychloroquine Cohort or Comparator Cohort.

All patients in the study will follow the same visit and assessment schedule. Following randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks 4, 12, and 24. Patients will not receive study drug during a 24-week withdrawal period between Weeks 25 and 48. Patients will also be scheduled to be assessed at an in person follow up visit at Week 36, and 48.

Eligibility criteria: Inclusion Criteria:

* 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;

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in urinary erythrocyte count(/HP)
timeFrame: Baseline to maximum 48 weeks
Secondary outcomes:
measure: Change in 24-hour urinary protein quantity
timeFrame: Baseline to maximum 48 weeks
measure: Change in urinary albumin characterization
timeFrame: Baseline to maximum 48 weeks
measure: Change in urinary albumin to creatinine ratio
timeFrame: Baseline to maximum 48 weeks
measure: Change in urinary erythrocyte count(urinary sediment analyzer)
timeFrame: Baseline to maximum 48 weeks
measure: Change in eGFR from baseline
timeFrame: Baseline to maximum 48 weeks
measure: Number of participants with treatment-related adverse events
timeFrame: Baseline to maximum 48 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Children's Hospital
name: Wen-yan Huang, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.