Alport SyndromePhase 2HERANCT02855268
Study of Lademirsen (SAR339375) in Patients With Alport Syndrome
A Phase 2 study testing lademirsen (SAR339375) in people with Alport Syndrome, run by Genzyme, a Sanofi Company at 23 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Alport Syndrome
- What is being tested?
- lademirsen (SAR339375)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 23 sitesin 7 countries
- Study dates
- 2 Nov 2019to 22 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female.
- Confirmed diagnosis of Alport syndrome
- Clinical diagnosis (hematuria, family history, hearing loss, ocular change), AND
- Genetic confirmation of Alport Syndrome in the participant or the family member, OR
- Kidney biopsy showing glomerular basement membrane abnormalities (e.g., significant thinning, thickening, irregularity or lucencies) consistent with Alport Syndrome.
- Age 18-55 years old.
Show all 17Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
United States5 sites
The Cleveland Clinic Foundation_Investigational Site Number :8400001
Cleveland, Ohio, 44195
Investigational Site Number :8400002
Los Angeles, California, 90024
University of Minnesota Childrens' Hospital_Investigational Site Number :8400003
Minneapolis, Minnesota, 55454
Columbia University Medical Center_Investigational Site Number :8400004
New York, New York, 10032
University of Utah_Investigational Site Number :8400005
Salt Lake City, Utah, 84132
Spain5 sites
Investigational Site Number :7240001
Barcelona, Barcelona [Barcelona], 08025
Investigational Site Number :7240004
Barcelona, Barcelona [Barcelona], 08035
Investigational Site Number :7240005
Córdoba, Andalusia, 14004
Investigational Site Number :7240003
Granada, 18014
Investigational Site Number :7240002
Madrid / Madrid, Madrid, Comunidad de, 28040
Australia3 sites
Investigational Site Number :0360003
Herston, Queensland, 4029
Investigational Site Number :0360002
Nedlands, Western Australia, 6009
Investigational Site Number :0360001
Parkville, Victoria, 3050
China3 sites
Investigational Site Number :1560001
Beijing, 100034
Investigational Site Number :1560002
Beijing, 100730
Investigational Site Number :1560004
Guangzhou, 510080
United Kingdom3 sites
Investigational Site Number :8260001
London, London, City of, NW3 2QG
Investigational Site Number :8260003
Newcastle upon Tyne, NE7 7DN
Investigational Site Number :8260002
Nottingham, Nottinghamshire, NG5 1PB
France2 sites
Investigational Site Number :2500001
Paris, 75015
Investigational Site Number :2500002
Toulouse, 31403
Germany2 sites
Uniklinik Köln, Innere Medizin II - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin_Investigational Site Number :2760001
Cologne, 50937
Universitätsmedizin Göttingen, Klinik für Nephrologie und Rheumatologie_Investigational Site Number :2760002
Göttingen, 37075
About this study
Official 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
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.
Read the 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
- Being tested
- lademirsen (SAR339375), Placebo
- Keywords
- Kidney disease, Nephritis, Hereditary nephritis, Hereditary kidney disease
- Medical subject headings
- Nephritis, Hereditary, Kidney Diseases, Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lademirsen (SAR339375)Drug
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection
PlaceboDrug
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Lademirsen | Experimental | 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). Receives: Drug: lademirsen (SAR339375) |
| Lademirsen/Lademirsen | Experimental | 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs with onset after the first dose of investigational medicinal product (IMP) or existing AEs that worsened during TEAE Period (for DB Period: from first IMP administration up to first administration in OLE period for participant who entered OLE period; and up to 7 days post last IMP administration for participant not continuing OLE period; for open-label: time from 1st IMP administration in open-label to last IMP administration+ 10 weeks).
Measured: 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)
DB Period: Annualized Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 48
Annualized change in eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (for participants with age greater than 16 years) as: eGFR=142*min(Scr/K, 1)α*max(Scr/K, 1)^-1.200*0.9938^Age*1.012 [if female], where Scr = serum creatinine in milligrams per deciliter (mg/dL), K = 0.7 for females (F) and 0.9 for males (M), α = -0.241(F) and -0.302(M); age=years, calculated at time of creatinine measurement. eGFR measurements collected from baseline to Week 48 were the response variable and included fixed effects of treatment (lademirsen or placebo), screening eGFR stratification factor (less than [<]60 versus greater than or equal to [>=]60 milliliters per minute per 1.73 meters squared [mL/min/1.73 m^2]), time, and treatment-by-time interaction. Least square (LS) mean and standard error (SE) estimated by linear mixed effect model.
Measured: Baseline, Week 48
Secondary outcomes (26)
DB Period: Absolute Change From Baseline in eGFR Values at Week 24 and 48
eGFR was used to measure level of kidney function and determine the stage of kidney disease. eGFR was calculated using CKD-EPI Creatinine Equation as: eGFR =142*min (Scr/K, 1) α*max (Scr/K, 1)^-1.200*0.9938^Age*1.012 [if female], where Scr was serum creatinine in mg/dL, K is 0.7 for females and 0.9 for males, α was -0.241 for females and -0.302 for males. Unit of age was years, calculated to reflect the age at the time when creatinine was measured.
Measured: Baseline, Weeks 24 and 48
DB Period: Percent Change From Baseline in eGFR Values at Week 24 and 48
eGFR was used to measure level of kidney function and determine the stage of kidney disease. eGFR was calculated using CKD-EPI Creatinine Equation as: eGFR =142*min (Scr/K, 1) α*max (Scr/K, 1)^-1.200*0.9938^Age*1.012 [if female], where Scr was serum creatinine in mg/dL, K is 0.7 for females and 0.9 for males, α was -0.241 for females and -0.302 for males. Unit of age was years, calculated to reflect the age at the time when creatinine was measured.
Measured: Baseline, Weeks 24 and 48
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48
Estimated glomerular filtration rate was used to measure level of kidney function and determine the stage of kidney disease. eGFR was calculated using CKD-EPI Creatinine Equation as: eGFR = 142*min(Scr/K,1)α*max(Scr/K,1)^-1.200*0.9938^Age*1.012 [if female], where Scr was serum creatinine in mg/dL, K is 0.7 for females and 0.9 for males, α was -0.241 for females and -0.302 for males. Number of participants with a reduction from baseline in eGFR value of <10%, <20%, <30%, or <40% at Weeks 24 and 48 were reported in this outcome measure.
Measured: At Weeks 24 and 48
DB Period: Number of Participants Who Developed End Stage Renal Disease (ESRD)
ESRD was defined as: eGFR <=15 mL/min/1.73 m^2; or initiation of hemodialysis; or receiving a renal transplantation during the double-blind treatment period.
Measured: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters
Criteria for PCSA included: Hemoglobin (Hb): <= 115 grams per liter (g/L) (Male), <= 95 g/L (Female); greater than or equal to (>=) 185 g/L (18.5 g/dL) (Male), >= 165 g/L (16.5g/dL) (Female); decrease from Baseline (DFB) = 20 g/L (2g/dL); Hematocrit: <= 0.37 volume/volume (v/v) (Male); <= 0.32 v/v (Female); >= 0.55 v/v (Male); >= 0.5 v/v (Female); Red Blood Cells (RBCs):>=6 Tera/ liter (L) and Platelets: <100 Giga/L; >= 700 Giga/L.
Measured: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline; Blood urea nitrogen: >=17 millimoles per liter (mmol/L); Uric acid: <120 micromol/L; >408 micromol/L; Creatinine clearance: <15 mL/min; >=15 to <30 mL/min; >=30 to <60 mL/min; >=60 to <90 mL/min; >=90 mL/min; eGFR: < 15 mL/min/1.73m^2; >=15 to <30 mL/min/1.73m^2; >=30 to <60 mL/min/1.73m^2; >=60 to <90 mL/min/1.73m^2; >=90 mL/min. Participants might be counted more than once for specified categories.
Measured: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Criteria for PCSA: Total bilirubin (TBILI): >1.5 upper limit of normal (ULN); >2 ULN; Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN; >20 ULN; Aspartate aminotransferase (AST): >3ULN; >5 ULN; >10 ULN; >20 ULN; Alkaline phosphatase: >1.5 ULN; ALT>3 ULN and TBILI>2 ULN and Direct Bilirubin> 35% TBILI and TBILI> 1.5 ULN.
Measured: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP):<=95 mmHg and DFB >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg; SBP (Orthostatic): <=-20mmHg; Diastolic blood pressure (DBP): <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg; DBP (Orthostatic): <=10 mmHg; heart rate (HR): <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB>=20 bpm and Weight: >=5% DFB; >=5% IFB.
Measured: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Criteria for potentially clinically significant ECG abnormalities: HR: <50 bpm; <50 bpm and DFB >=20 bpm; <40 bpm; <40 bpm and DFB >=20 bpm; <30 bpm; <30 bpm and DFB >=20 bpm; >90 bpm; >=90 bpm and IFB >=20 bpm; >100 bpm; >=100bpm and IFB >=20 bpm; >120 bpm; >=120 bpm and IFB >=20 bpm; PR Interval: >200 millisecond(ms); >200 ms and IFB >=25%; >220 ms; >220 ms and IFB >=25%; >240 ms; >240 ms and IFB>=25%; QRS Interval: >110 ms; >110 ms and IFB >=25%; >120 ms; >120 ms and IFB >=25%; QT Interval: >500 ms and QTc Fridericia (QTc F): >450 ms; >480 ms; >500 ms; IFB >30 and <=60 ms; IFB >60 ms.
Measured: From Baseline up to Week 48
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005)
Post-dose (4 hours) plasma concentration of lademirsen, its active major metabolite (RG0005), and SUM (lademirsen+RG0005) on Day 1, and at Weeks 24 and 48 are reported in the outcome measure. 4-hour SUM concentrations are calculated values (sum of measured lademirsen+RG0005).
Measured: Post-dose (4 hours) on Day 1, Weeks 24 and 48
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005)
Ctrough was measured from the pre-dose (up to 4 hours before study drug administration) plasma samples collected at Weeks 4, 12, 24, 36 and 48. SUM concentrations (lademirsen+RG0005) are measured values (assay measures lademirsen+ RG0005).
Measured: Pre-dose (up to 4 hours before study drug administration) on Weeks 4, 12, 24, 36 and 48
DB Period: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) Response
ADA responses were categorized as: treatment-induced, and treatment-boosted response. Participant whose ADA status was negative at baseline but positive (ADA titer value >=50) anytime post-baseline or missing at baseline was considered to have treatment-induced ADA. Participant whose ADA status was positive at baseline (pre-existing ADA) and the ADA titer level anytime post-baseline was significantly higher (>= twice the minimum required dilution) than that at baseline was considered to have treatment-boosted ADA.
Measured: 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)
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Anti-drug Antibody (ADA) Responses
TEAEs: AE developed/worsened/became serious during TEAE period (from first IMP administration in DB period to first administration in OLE period for those who entered OLE (i.e., up to W48), up to 7 days post last dose for those not continuing to OLE period (i.e., up to W49). TESAEs: any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization/prolongation of hospitalization, resulted in persistent/significant disability, was a congenital anomaly/birth defect, or a medically important event. ADA response was categorized as treatment-induced (participant whose ADA status was positive [ADA titer value >=50] anytime post-baseline and was negative/missing at baseline), treatment-boosted (participant whose ADA status was positive at baseline \& ADA titer level anytime post-baseline was significantly higher). In this outcome measure, number of participants with TEAEs as per ADA responses (positive or negative) were reported.
Measured: 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)
DB Period: Change From Baseline in Circulating MicroRNA-21 at Weeks 24 and 48
Circulating microRNA-21 were the supportive biomarkers assessed in study.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Urea Nitrogen (BUN) Values at Weeks 24 and 48
BUN was the supportive biomarker assessed during the study. Change from Baseline in BUN at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 24 and 48
Urine protein and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine protein to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Albumin/Creatinine Ratio at Weeks 24 and 48
Urine albumin and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine albumin to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Epidermal Growth Factor (EGF)/Creatinine Ratio at Weeks 24 and 48
EGF and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine EGF to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Creatinine Values at Weeks 24 and 48
Creatinine was the supportive biomarker assessed during the study. Change from Baseline in blood creatinine values at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Creatinine Values at Weeks 24 and 48
Creatinine was the supportive biomarker assessed during the study. Change from Baseline in urine creatinine values at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Cystatine C Values at Weeks 24 and 48
Cystatine C was the supportive biomarker assessed during the study. Change from Baseline in blood cystatine C values at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Cystatin C/Creatinine Ratio at Weeks 24 and 48
Cystatin C and Creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine cystatin C to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Transforming Growth Factor Beta 1 Values at Week 24 and 48
Transforming growth factor beta 1 was the supportive biomarker assessed during the study. Change from Baseline in blood transforming growth factor beta 1 values at Week 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Transforming Growth Factor Beta 1/Creatinine Ratio at Week 24 and 48
Transforming growth factor beta 1 and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine transforming growth factor beta 1 to creatinine ratio at Week 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Lipocalin-2 Values at Weeks 24 and 48
Blood Lipocalin-2 was the supportive biomarker assessed during the study. Change from Baseline in blood lipocalin-2 at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Lipocalin-2/Creatinine Ratio at Weeks 24 and 48
Lipocalin-2 and Creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine lipocalin-2 to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.
Measured: Baseline, Weeks 24 and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2016 (estimated)
- Study start2 Nov 2019
- Primary completion22 Sep 2022
- Study completion22 Sep 2022
Why it stopped: The results of the futility analysis led to the study termination. No unexpected safety findings were identified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alport SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02855268
- Sponsor's protocol ID
- ACT16248
- Other IDs
- 2019-004394-10, 2019
- Acronym
- HERA
- Status last verified
- Sep 2025
- First submitted
- 28 Jul 2016
- Last updated
- 11 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 38829703Kashtan 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.
PubMed 33159213
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02855268
- Acronym / sponsor ID
- HERA / ACT16248
- Conditions
- Alport Syndrome
- Keywords
- Kidney disease, Nephritis, Hereditary nephritis, Hereditary kidney disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The results of the futility analysis led to the study termination. No unexpected safety findings were identified.
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2019 (actual)
- Primary completion
- 22 Sep 2022 (actual)
- Study completion
- 22 Sep 2022 (actual)
- First posted
- 4 Aug 2016 (estimated)
- Results
- Posted 23 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo/Lademirsen | Experimental | Drug: lademirsen (SAR339375)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). |
| Lademirsen/Lademirsen | Experimental | Drug: PlaceboParticipants 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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Male or female.
- Confirmed diagnosis of 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):
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lademirsen (SAR339375)Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection | Drug | Placebo/Lademirsen |
| PlaceboPharmaceutical form: Solution for injection Route of administration: Subcutaneous injection | Drug | Lademirsen/Lademirsen |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: 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)
Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs with onset after the first dose of investigational medicinal product (IMP) or existing AEs that worsened during TEAE Period (for DB Period: from first IMP administration up to first administration in OLE period for participant who entered OLE period; and up to 7 days post last IMP administration for participant not continuing OLE period; for open-label: time from 1st IMP administration in open-label to last IMP administration+ 10 weeks).
DB Period: Annualized Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 48
Time frame: Baseline, Week 48
Annualized change in eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (for participants with age greater than 16 years) as: eGFR=142*min(Scr/K, 1)α*max(Scr/K, 1)^-1.200*0.9938^Age*1.012 [if female], where Scr = serum creatinine in milligrams per deciliter (mg/dL), K = 0.7 for females (F) and 0.9 for males (M), α = -0.241(F) and -0.302(M); age=years, calculated at time of creatinine measurement. eGFR measurements collected from baseline to Week 48 were the response variable and included fixed effects of treatment (lademirsen or placebo), screening eGFR stratification factor (less than [<]60 versus greater than or equal to [>=]60 milliliters per minute per 1.73 meters squared [mL/min/1.73 m^2]), time, and treatment-by-time interaction. Least square (LS) mean and standard error (SE) estimated by linear mixed effect model.
26 secondary outcomes
DB Period: Absolute Change From Baseline in eGFR Values at Week 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Percent Change From Baseline in eGFR Values at Week 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48
Time frame: At Weeks 24 and 48
DB Period: Number of Participants Who Developed End Stage Renal Disease (ESRD)
Time frame: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters
Time frame: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Time frame: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Time frame: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Time frame: From Baseline up to Week 48
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Time frame: From Baseline up to Week 48
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005)
Time frame: Post-dose (4 hours) on Day 1, Weeks 24 and 48
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005)
Time frame: Pre-dose (up to 4 hours before study drug administration) on Weeks 4, 12, 24, 36 and 48
DB Period: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) Response
Time frame: 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)
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Anti-drug Antibody (ADA) Responses
Time frame: 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)
DB Period: Change From Baseline in Circulating MicroRNA-21 at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Urea Nitrogen (BUN) Values at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Albumin/Creatinine Ratio at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Epidermal Growth Factor (EGF)/Creatinine Ratio at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Creatinine Values at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Creatinine Values at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Cystatine C Values at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Cystatin C/Creatinine Ratio at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Transforming Growth Factor Beta 1 Values at Week 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Transforming Growth Factor Beta 1/Creatinine Ratio at Week 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Blood Lipocalin-2 Values at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
DB Period: Change From Baseline in Urine Lipocalin-2/Creatinine Ratio at Weeks 24 and 48
Time frame: Baseline, Weeks 24 and 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38829703Gale 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.
- Derived from this study: PubMed 33159213Kashtan 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.
- ACT16248 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
Related trials for Alport Syndrome
Active, not recruitingPhase 2
A Study to Learn About How Well BAY 3401016 Works in Adults With Alport Syndrome
Alport Syndrome
Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
RecruitingPhase 3
Phase 3 Clinical Trial With Dapagliflozin in Chronic Kidney Disease in Adolescents and Young Adult Patients
Chronic Kidney Failure in Children and Young Adults
RecruitingPhase 2
EXACT Study: A Blinded Study in Patients With Alport Syndrome to Evaluate Exaluren Efficacy and Safety
Alport Syndrome, X-Linked, Alport Syndrome, Autosomal Recessive
RecruitingObservational study
Eurbio-Alport (RaDiCo Cohort) (RaDiCo Eurbio-Alport)
Alport Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lademirsen (SAR339375) in people with Alport Syndrome, run by Genzyme, a Sanofi Company at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Spain, Australia, China, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02855268, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.