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

Registration Number
NCT04937907
Lead Sponsor
Shanghai Children's Hospital
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Hydroxychloroquine CohortBenazepril hydrochloride 10 milligram (mg) TabPatients 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).
Hydroxychloroquine CohortHydroxychloroquine Sulfate 100 milligram (mg) TabPatients 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).
Comparator CohortBenazepril hydrochloride 10 milligram (mg) TabDuring treatment with HCQ, Patients randomized to Comparator Cohort only received enalapril(5-10mg qd).
Primary Outcome Measures
NameTimeMethod
Change in urinary erythrocyte count(/HP)Baseline to maximum 48 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Change in eGFR from baselineBaseline to maximum 48 weeks

To assess the increase in eGFR from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort.

Change in urinary albumin characterizationBaseline to maximum 48 weeks

To assess the change in urinary albumin characterization from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort.

Change in urinary erythrocyte count(urinary sediment analyzer)Baseline to maximum 48 weeks

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

Number of participants with treatment-related adverse eventsBaseline to maximum 48 weeks

Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 48 weeks.

Change in 24-hour urinary protein quantityBaseline to maximum 48 weeks

To assess the change in 24-hour urinary protein quantity from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort.

Change in urinary albumin to creatinine ratioBaseline to maximum 48 weeks

To assess the change in urinary albumin to creatinine ratio from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort.

Trial Locations

Locations (1)

Shanghai Children's Hospital

🇨🇳

Shanghai, Shanghai, China

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