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

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.

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.