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

NCT ID: NCT04937907

Last Updated: 2023-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-08

Study Completion Date

2024-12-31

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.

Conditions

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Alport Syndrome, X-Linked

Keywords

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Alport Syndrome Hydroxychloroquine Treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hydroxychloroquine Cohort

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).

Group Type EXPERIMENTAL

Hydroxychloroquine Sulfate 100 milligram (mg) Tab

Intervention Type DRUG

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

Benazepril hydrochloride 10 milligram (mg) Tab

Intervention Type DRUG

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

Comparator Cohort

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

Group Type SHAM_COMPARATOR

Benazepril hydrochloride 10 milligram (mg) Tab

Intervention Type DRUG

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

Interventions

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Hydroxychloroquine Sulfate 100 milligram (mg) Tab

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

Intervention Type DRUG

Benazepril hydrochloride 10 milligram (mg) Tab

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

Intervention Type DRUG

Other Intervention Names

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HCQ Benazepril

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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wen-yan Huang, PhD

Role: STUDY_DIRECTOR

Shanghai Children's Hospital

Locations

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Shanghai Children's Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wen-yan Huang, PhD

Role: CONTACT

Phone: +8618964025491

Email: [email protected]

Lei Sun, MD

Role: CONTACT

Phone: +8618817821787

Email: [email protected]

Facility Contacts

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Wen-yan Huang, PHD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 25388007 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31754267 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32034323 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31382914 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30922594 (View on PubMed)

Other Identifiers

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2019YLYM06

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2021SPNR001

Identifier Type: -

Identifier Source: org_study_id