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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Hydroxychloroquine in Patients With X-linked Alport Syndrome in China (CHXLAS)

Conditions
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Alport Syndrome, X-Linked

Intervention / Treatment
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* Drug: Hydroxychloroquine Sulfate 100 milligram (mg) Tab
* Drug: Benazepril hydrochloride 10 milligram (mg) Tab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine Cohort<br>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<br>* Patients administered HCQ by oral at a dose of 6.5mg per kilogram twice a day at least 6 months.<br>* Other names: HCQ;Drug: Benazepril hydrochloride 10 milligram (mg) Tab<br>* Patients administered Benazepril by oral at a dose of 5mg or 10mg once a day at least 6 months.<br>* Other names: Benazepril;|
| Sham Comparator: Comparator Cohort<br>During treatment with HCQ, Patients randomized to Comparator Cohort only received enalapril(5-10mg qd). | Drug: Benazepril hydrochloride 10 milligram (mg) Tab<br>* Patients administered Benazepril by oral at a dose of 5mg or 10mg once a day at least 6 months.<br>* Other names: Benazepril;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour urinary protein quantity | 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. | Baseline to maximum 48 weeks | 
| Change in urinary albumin characterization | To assess the change in urinary albumin characterization from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort. | Baseline to maximum 48 weeks | 
| Change in urinary albumin to creatinine ratio | 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. | Baseline to maximum 48 weeks | 
| Change in urinary erythrocyte count(urinary sediment analyzer) | 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. | Baseline to maximum 48 weeks | 
| Change in eGFR from baseline | To assess the increase in eGFR from baseline to week 48 for patients receiving active drug, compared to patients in Comparator Cohort. | Baseline to maximum 48 weeks | 
| Number of participants with treatment-related adverse events | Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 48 weeks. | Baseline to maximum 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alport Syndrome, Hydroxychloroquine, Treatment