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

Primary Purpose

Alport Syndrome, X-Linked

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Hydroxychloroquine Sulfate 100 milligram (mg) Tab

Benazepril hydrochloride 10 milligram (mg) Tab

About this trial

This is an interventional treatment trial for Alport Syndrome, X-Linked focused on measuring Alport Syndrome, Hydroxychloroquine, Treatment

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Shanghai Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Hydroxychloroquine Cohort

Comparator Cohort

Arm Description

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).

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04937907

First Posted

June 17, 2021

Last Updated

September 8, 2021

Sponsor

Shanghai Children's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04937907

Brief Title

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

Acronym

CHXLAS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 8, 2021 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alport Syndrome, X-Linked

Keywords

Alport Syndrome, Hydroxychloroquine, Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hydroxychloroquine Cohort

Arm Type

Experimental

Arm Description

Arm Title

Comparator Cohort

Arm Type

Sham Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Hydroxychloroquine Sulfate 100 milligram (mg) Tab

Other Intervention Name(s)

HCQ

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Benazepril hydrochloride 10 milligram (mg) Tab

Other Intervention Name(s)

Benazepril

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in urinary erythrocyte count(/HP)

Description

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.

Time Frame

Baseline to maximum 48 weeks

Secondary Outcome Measure Information:

Title

Change in 24-hour urinary protein quantity

Description

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.

Time Frame

Baseline to maximum 48 weeks

Title

Change in urinary albumin characterization

Description

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

Time Frame

Baseline to maximum 48 weeks

Title

Change in urinary albumin to creatinine ratio

Description

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.

Time Frame

Baseline to maximum 48 weeks

Title

Change in urinary erythrocyte count(urinary sediment analyzer)

Description

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.

Time Frame

Baseline to maximum 48 weeks

Title

Change in eGFR from baseline

Description

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

Time Frame

Baseline to maximum 48 weeks

Title

Number of participants with treatment-related adverse events

Description

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

Time Frame

Baseline to maximum 48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wen-yan Huang, PhD

Phone

+8618964025491

huangwenyan@sjtu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Lei Sun, MD

Phone

+8618817821787

sunlei@shchildren.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wen-yan Huang, PhD

Organizational Affiliation

Shanghai Children's Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Shanghai Children's Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200062

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wen-yan Huang, PHD

Phone

+8618964025491

huangwenyan@sjtu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25388007

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.

Results Reference

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PubMed Identifier

31754267

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. Erratum In: Eur J Hum Genet. 2023 Jan 18;:

Results Reference

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PubMed Identifier

32034323

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.

Results Reference

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PubMed Identifier

31382914

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.

Results Reference

background

PubMed Identifier

30922594

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.

Results Reference

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

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