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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02855268




Registration number
NCT02855268
Ethics application status
Date submitted
28/07/2016
Date registered
4/08/2016

Titles & IDs
Public title
Study of Lademirsen (SAR339375) in Patients With Alport Syndrome
Scientific title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, Pharmacodynamics, and Pharmacokinetics of Lademirsen (SAR339375) for Subcutaneous Injection Administered Every Week in Patients With Alport Syndrome
Secondary ID [1] 0 0
2019-004394-10
Secondary ID [2] 0 0
ACT16248
Universal Trial Number (UTN)
Trial acronym
HERA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alport Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lademirsen (SAR339375)
Treatment: Drugs - Placebo

Experimental: 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).

Experimental: 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).


Treatment: Drugs: lademirsen (SAR339375)
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection

Treatment: Drugs: Placebo
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
DB: from 1st dose of IMP upto 1st dose of IMP in OLE for participant who entered OLE (Week 48); up to 7 days post last dose for participant not continuing to OLE (Week 49); OLE:1st dose of IMP (at Week 48) in OLE upto 10 weeks post last dose (Week 106)
Primary outcome [2] 0 0
DB Period: Annualized Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 48
Timepoint [2] 0 0
Baseline, Week 48
Secondary outcome [1] 0 0
DB Period: Absolute Change From Baseline in eGFR Values at Week 24 and 48
Timepoint [1] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [2] 0 0
DB Period: Percent Change From Baseline in eGFR Values at Week 24 and 48
Timepoint [2] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [3] 0 0
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48
Timepoint [3] 0 0
At Weeks 24 and 48
Secondary outcome [4] 0 0
DB Period: Number of Participants Who Developed End Stage Renal Disease (ESRD)
Timepoint [4] 0 0
From Baseline up to Week 48
Secondary outcome [5] 0 0
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters
Timepoint [5] 0 0
From Baseline up to Week 48
Secondary outcome [6] 0 0
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Timepoint [6] 0 0
From Baseline up to Week 48
Secondary outcome [7] 0 0
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Timepoint [7] 0 0
From Baseline up to Week 48
Secondary outcome [8] 0 0
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Timepoint [8] 0 0
From Baseline up to Week 48
Secondary outcome [9] 0 0
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Timepoint [9] 0 0
From Baseline up to Week 48
Secondary outcome [10] 0 0
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005)
Timepoint [10] 0 0
Post-dose (4 hours) on Day 1, Weeks 24 and 48
Secondary outcome [11] 0 0
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005)
Timepoint [11] 0 0
Pre-dose (up to 4 hours before study drug administration) on Weeks 4, 12, 24, 36 and 48
Secondary outcome [12] 0 0
DB Period: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) Response
Timepoint [12] 0 0
From first IMP administration (Day 1) up to first administration in OLE period for participant who entered OLE period (i.e., up to W48) & up to 7 days post last IMP administration for participant not continuing OLE period (i.e., up to W49)
Secondary outcome [13] 0 0
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Anti-drug Antibody (ADA) Responses
Timepoint [13] 0 0
From first IMP administration (Day 1) up to first administration in OLE period for participant who entered OLE period (i.e., up to W48) & up to 7 days post last IMP administration for participant not continuing OLE period (i.e., up to W49)
Secondary outcome [14] 0 0
DB Period: Change From Baseline in Circulating MicroRNA-21 at Weeks 24 and 48
Timepoint [14] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [15] 0 0
DB Period: Change From Baseline in Blood Urea Nitrogen (BUN) Values at Weeks 24 and 48
Timepoint [15] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [16] 0 0
DB Period: Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 24 and 48
Timepoint [16] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [17] 0 0
DB Period: Change From Baseline in Urine Albumin/Creatinine Ratio at Weeks 24 and 48
Timepoint [17] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [18] 0 0
DB Period: Change From Baseline in Urine Epidermal Growth Factor (EGF)/Creatinine Ratio at Weeks 24 and 48
Timepoint [18] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [19] 0 0
DB Period: Change From Baseline in Blood Creatinine Values at Weeks 24 and 48
Timepoint [19] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [20] 0 0
DB Period: Change From Baseline in Urine Creatinine Values at Weeks 24 and 48
Timepoint [20] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [21] 0 0
DB Period: Change From Baseline in Blood Cystatine C Values at Weeks 24 and 48
Timepoint [21] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [22] 0 0
DB Period: Change From Baseline in Urine Cystatin C/Creatinine Ratio at Weeks 24 and 48
Timepoint [22] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [23] 0 0
DB Period: Change From Baseline in Blood Transforming Growth Factor Beta 1 Values at Week 24 and 48
Timepoint [23] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [24] 0 0
DB Period: Change From Baseline in Urine Transforming Growth Factor Beta 1/Creatinine Ratio at Week 24 and 48
Timepoint [24] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [25] 0 0
DB Period: Change From Baseline in Blood Lipocalin-2 Values at Weeks 24 and 48
Timepoint [25] 0 0
Baseline, Weeks 24 and 48
Secondary outcome [26] 0 0
DB Period: Change From Baseline in Urine Lipocalin-2/Creatinine Ratio at Weeks 24 and 48
Timepoint [26] 0 0
Baseline, Weeks 24 and 48

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2022
Sample size
Target
Accrual to date
Final
43
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Investigational Site Number :0360003 - Herston
Recruitment hospital [2] 0 0
Investigational Site Number :0360001 - Parkville
Recruitment hospital [3] 0 0
Investigational Site Number :0360002 - Nedlands
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Utah
Country [6] 0 0
China
State/province [6] 0 0
Beijing
Country [7] 0 0
China
State/province [7] 0 0
Guangzhou
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Toulouse
Country [10] 0 0
Germany
State/province [10] 0 0
Göttingen
Country [11] 0 0
Germany
State/province [11] 0 0
Köln
Country [12] 0 0
Spain
State/province [12] 0 0
Andalucia
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona [Barcelona]
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid, Comunidad De
Country [15] 0 0
Spain
State/province [15] 0 0
Granada
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London, City Of
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Nottinghamshire
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02855268