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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02855268
Ethics application status
Date submitted
28/07/2016
Date registered
4/08/2016
Date last updated
14/09/2020

Titles & IDs
Public title
Study of 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 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's 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: Lademirsen (SAR339375) - Eligible participants will receive subcutaneous injection every week for 48 weeks

Placebo Comparator: Placebo - Eligible participants will receive subcutaneous injection every week for 48 weeks


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 adverse events - Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Timepoint [1] 0 0
Baseline to maximum 102 weeks
Primary outcome [2] 0 0
Annualized change in estimated glomerular filtration rate eGFR from baseline - Annualized change in estimated glomerular filtration rate eGFR from baseline to 48 weeks
Timepoint [2] 0 0
Baseline to 48 weeks
Secondary outcome [1] 0 0
Pharmacokinetics (PK) : Maximum concentration in plasma (Cmax) - Plasma concentrations (Cmax) of parent SAR339375 and its metabolites
Timepoint [1] 0 0
24 weeks and 48 weeks
Secondary outcome [2] 0 0
Pharmacokinetics (PK) : Trough plasma concentration (Ctrough) - Plasma concentrations (Ctrough) of parent SAR339375 and its metabolites
Timepoint [2] 0 0
24 weeks and 48 weeks
Secondary outcome [3] 0 0
Number of participants with anti-drug antibodies (ADAs) - Number of participants with ADAs incidents and titer
Timepoint [3] 0 0
Baseline to maximum 102 weeks
Secondary outcome [4] 0 0
Number of participant with adverse events associated to ADAs - Association of ADAs with adverse events per participants will be collected.
Timepoint [4] 0 0
Baseline to maximum 102 weeks
Secondary outcome [5] 0 0
Percent change in eGFR values - Percent change in eGFR values from baseline to 24 weeks and 48 weeks
Timepoint [5] 0 0
Baseline to 24 weeks and 48 weeks
Secondary outcome [6] 0 0
Proportion of subjects who reach end staged renal disease (ESRD) - Proportion of participants who reach ESRD as defined by an eGFR =15 mL/min/1.73 m^2 or initiation of hemodialysis or renal transplantation from baseline to 48 weeks -
Timepoint [6] 0 0
Baseline to 48 weeks

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 subject or the family member, OR

3. Kidney biopsy showing glomerular basement membrane abnormalities (eg, 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 (patients must meet 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 should be
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 subjects of childbearing potential and sexually mature male
subjects must agree 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, subjects prescribed benzodiazepines, cannabinoids, or
opiates with positive results on a drug screen may be 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 willing
to comply with all aspects of the protocol
Minimum age
18 Years
Maximum age
55 Years
Gender
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)

- 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 subject's
study compliance; confound the study results; impact subject 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 subject'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 is
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 (eg, other oligonucleotide products)

- Any other condition or circumstance that, in the opinion of the Investigator, may make
the subject unlikely to complete the study or comply with study procedures and
requirements, or may pose a risk to the subject's safety and well-being

The above information is not intended to contain all considerations relevant to a patient'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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360003 - Herston
Recruitment hospital [2] 0 0
Investigational Site Number 0360001 - Parkville
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Minnesota
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
China
State/province [4] 0 0
Beijing
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Toulouse
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Newcastle Upon Tyne
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objectives:

- To assess the efficacy of SAR339375 in reducing the decline in renal function

- To assess the safety and tolerability of SAR339375

Secondary Objectives:

- To assess plasma pharmacokinetic (PK) parameters of the parent compound and its
metabolites

- To assess the immunogenicity of the SAR339375
Trial website
https://clinicaltrials.gov/show/NCT02855268
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
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02855268