Study of Lademirsen (SAR339375) in Patients With Alport Syndrome

NCT ID: NCT02855268

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-02
• Study Completion Date: 2022-09-22

Brief Summary

Primary Objectives:

• To assess the efficacy of lademirsen (SAR339375) in reducing the decline in renal function.
• To assess the safety and tolerability of lademirsen (SAR339375) in participants with Alport syndrome.

Secondary Objectives:

• To assess plasma pharmacokinetic (PK) parameters of the parent compound and its active major metabolite.
• To assess the potential formation of anti-drug antibodies (ADAs) following administration of lademirsen (SAR339375).
• To assess the pharmacodynamic effect of lademirsen (SAR339375) on miR-21 and on changes in renal injury and function biomarkers.

Detailed Description

The planned length of participation in the study for each participant was up to approximately 110 weeks (from screening through completion of follow-up). This included:

• Screening/baseline period of up to 4 weeks
• Double-blind, placebo-controlled treatment period of 48 weeks
• Open-label extension treatment period of 48 weeks (all participant to enter a 48-week open label extension period and receive active treatment with lademirsen [SAR339375]).
• Post-treatment follow-up period of 10 weeks.

Conditions

Alport Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo/Lademirsen

Participants received subcutaneous (SC) doses of placebo (matched to lademirsen) every week (QW) during the 48 weeks of double blind (DB) treatment period. Participants who received placebo and completed DB treatment period entered in open-label extension (OLE) treatment period and received lademirsen at a dose of 110 milligrams (mg) QW for an additional 48 weeks (i.e., up to Week 96).

Group Type: EXPERIMENTAL

lademirsen (SAR339375)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Lademirsen/Lademirsen

Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. Participants who completed DB treatment period entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Interventions

lademirsen (SAR339375)

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female.
• Confirmed diagnosis of Alport syndrome

1. Clinical diagnosis (hematuria, family history, hearing loss, ocular change), AND

2. Genetic confirmation of Alport Syndrome in the participant or the family member, OR

3. Kidney biopsy showing glomerular basement membrane abnormalities (e.g., significant thinning, thickening, irregularity or lucencies) consistent with Alport Syndrome.

• Age 18-55 years old.
• eGFR > 35 ml/min/1.73m^2 and <90 mL/min/1.73m^2 (based on CKD-EPI) at screening.
• Renal Function Criteria (participants must have met at least one of the following CRITERIA A, B or C):

• A) Decline in eGFR of >=4 mL/min/1.73 m^2/year (eGFR slope <= -4) based on a linear regression slope analysis of >=4 eGFR measurements within 3 years prior to the study and with a minimum of 2-year time span (the last, of the screening measurement, and first eGFR measurements should be separated by at least 2 years). eGFR was calculated by using either the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
• B) proteinuria (UPCR) >2000 mg/g (UACR>1000 mg/g).
• C) Age and sex adjusted eGFR (based on CKD-Epi; male 18-23 eGFR<90 mL/min/1.73m^2
• ACE inhibitor and/or ARB, the dosing regimen should be stable for at least 30 days prior to screening.
• Sexually active female participants of childbearing potential and sexually mature male participants must have agreed to practice true abstinence in line with their preferred and usual lifestyle or to use two acceptable effective methods of contraception for the entire duration of the study and for at least 6 weeks after last dose.
• Negative drug screen for opiates, cocaine, heroin, phencyclidine, amphetamines (including ecstasy), barbiturates, benzodiazepines, and cannabinoids. At the Investigator's discretion, participants prescribed benzodiazepines, cannabinoids, or opiates with positive results on a drug screen were allowed.
• Negative screening results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV) antibody.
• Normal biological tests.
• Able to understand all study procedures in the informed consent form (ICF) and to comply with all aspects of the protocol.

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).
• End stage renal disease (ESRD) as evidenced by ongoing dialysis therapy or history of renal transplantation.
• Any clinically significant illness within 30 days before screening or surgical or medical condition (other than Alport syndrome) that could interfere with the participant's study compliance; confound the study results; impact participant safety; or significantly alter the absorption, distribution, metabolism, or excretion of drugs.
• Weight > 110 kg.
• Any history of active malignancy within the last 1 year (history of localized basal cell or squamous cell carcinoma and cervical carcinoma in situ that has been excised/appropriately treated or a fully excised malignant lesion with a low probability of recurrence will not be considered exclusionary).
• Prior treatment with Bardoxolone within 90 days prior to screening.
• History or presence of alcoholism or drug abuse within 2 years before screening or other concurrent social conditions that would potentially interfere with the participant's study compliance, at the discretion of the Investigator.
• Participation in a recent investigational study and receipt of an investigational drug or investigational use of a licensed drug within 30 days or 5 half-lives, whichever was longer, prior to screening.
• History or presence of hypersensitivity or idiosyncratic, allergic, or other clinically significant reaction to the study drug (including placebo), inactive ingredients, or related compounds (e.g., other oligonucleotide products).
• Any other condition or circumstance that, in the opinion of the Investigator, may make the participant unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the participant's safety and well-being.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number :8400002

Los Angeles, California, United States

University of Minnesota Childrens' Hospital_Investigational Site Number :8400003

Minneapolis, Minnesota, United States

Columbia University Medical Center_Investigational Site Number :8400004

New York, New York, United States

The Cleveland Clinic Foundation_Investigational Site Number :8400001

Cleveland, Ohio, United States

University of Utah_Investigational Site Number :8400005

Salt Lake City, Utah, United States

Investigational Site Number :0360003

Herston, Queensland, Australia

Investigational Site Number :0360001

Parkville, Victoria, Australia

Investigational Site Number :0360002

Nedlands, Western Australia, Australia

Investigational Site Number :1560001

Beijing, , China

Investigational Site Number :1560002

Beijing, , China

Investigational Site Number :1560004

Guangzhou, , China

Investigational Site Number :2500001

Paris, , France

Investigational Site Number :2500002

Toulouse, , France

Uniklinik Köln, Innere Medizin II - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin_Investigational Site Number :2760001

Cologne, , Germany

Universitätsmedizin Göttingen, Klinik für Nephrologie und Rheumatologie_Investigational Site Number :2760002

Göttingen, , Germany

Investigational Site Number :7240005

Córdoba, Andalusia, Spain

Investigational Site Number :7240001

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240004

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240002

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240003

Granada, , Spain

Investigational Site Number :8260001

London, London, City of, United Kingdom

Investigational Site Number :8260002

Nottingham, Nottinghamshire, United Kingdom

Investigational Site Number :8260003

Newcastle upon Tyne, , United Kingdom

Countries

United States; Australia; China; France; Germany; Spain; United Kingdom

References

Gale DP, Gross O, Wang F, Esteban de la Rosa RJ, Hall M, Sayer JA, Appel G, Hariri A, Liu S, Maski M, Shen Y, Zhang Q, Iqbal S, Kowthalam MU, Lin J, Ding J; HERA Clinical Trial Group. A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome. Clin J Am Soc Nephrol. 2024 Aug 1;19(8):995-1004. doi: 10.2215/CJN.0000000000000458. Epub 2024 Jun 3.

Reference Type: DERIVED

PMID: 38829703 (View on PubMed)

Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.

Reference Type: DERIVED

PMID: 33159213 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25190&tenant=MT_SNY_9011

ACT16248 Plain Language Results Summary

Other Identifiers

2019-004394-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT16248

Identifier Type: -

Identifier Source: org_study_id