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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-004394-10 | EudraCT Number |
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The results of the futility analysis led to the study termination. No unexpected safety findings were identified.
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Primary Objectives:
Secondary Objectives:
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lademirsen (SAR339375) | Drug | Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. | Baseline, Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion criteria:
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):
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:
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number :8400002 | Los Angeles | California | 90024 | United States | ||
| University of Minnesota Childrens' Hospital_Investigational Site Number :8400003 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38829703 | Derived | 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. | |
| 33159213 |
| Label | URL |
|---|---|
| ACT16248 Plain Language Results Summary | View source |
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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
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The study was planned with 2 Stages/Cohorts. Since the study was terminated early, Stage 2/Cohort 2 was not conducted. In Stage 1 analysis of double blind (DB) period performed until 48 weeks. In Stage 1 open label extension (OLE) period, only safety data was collected and assessed due to early study termination.
The study was conducted at 20 active centers in 7 countries. A total of 67 participants were screened between 02 November 2019 and 30 December 2021, out of which 43 participants were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/Lademirsen | Participants received subcutaneous (SC) doses of placebo (matched to lademirsen) every week (QW) during the 48 weeks of DB treatment period. Participants who received placebo and completed DB treatment period entered in 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| DB Period (up to 48 Weeks) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 8, 2021 | Sep 8, 2023 |
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| Placebo | Drug | Pharmaceutical form: Solution for injection Route of administration: Subcutaneous injection |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline, Weeks 24 and 48 |
| Minneapolis |
| Minnesota |
| 55454 |
| United States |
| Columbia University Medical Center_Investigational Site Number :8400004 | New York | New York | 10032 | United States |
| The Cleveland Clinic Foundation_Investigational Site Number :8400001 | Cleveland | Ohio | 44195 | United States |
| University of Utah_Investigational Site Number :8400005 | Salt Lake City | Utah | 84132 | United States |
| Investigational Site Number :0360003 | Herston | Queensland | 4029 | Australia |
| Investigational Site Number :0360001 | Parkville | Victoria | 3050 | Australia |
| Investigational Site Number :0360002 | Nedlands | Western Australia | 6009 | Australia |
| Investigational Site Number :1560001 | Beijing | 100034 | China |
| Investigational Site Number :1560002 | Beijing | 100730 | China |
| Investigational Site Number :1560004 | Guangzhou | 510080 | China |
| Investigational Site Number :2500001 | Paris | 75015 | France |
| Investigational Site Number :2500002 | Toulouse | 31403 | France |
| Uniklinik Köln, Innere Medizin II - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin_Investigational Site Number :2760001 | Cologne | 50937 | Germany |
| Universitätsmedizin Göttingen, Klinik für Nephrologie und Rheumatologie_Investigational Site Number :2760002 | Göttingen | 37075 | Germany |
| Investigational Site Number :7240005 | Córdoba | Andalusia | 14004 | Spain |
| Investigational Site Number :7240001 | Barcelona | Barcelona [Barcelona] | 08025 | Spain |
| Investigational Site Number :7240004 | Barcelona | Barcelona [Barcelona] | 08035 | Spain |
| Investigational Site Number :7240002 | Madrid / Madrid | Madrid, Comunidad de | 28040 | Spain |
| Investigational Site Number :7240003 | Granada | 18014 | Spain |
| Investigational Site Number :8260001 | London | London, City of | NW3 2QG | United Kingdom |
| Investigational Site Number :8260002 | Nottingham | Nottinghamshire | NG5 1PB | United Kingdom |
| Investigational Site Number :8260003 | Newcastle upon Tyne | NE7 7DN | United Kingdom |
| Derived |
| 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. |
| FG001 |
| 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). |
| COMPLETED |
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| NOT COMPLETED |
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| OLE Period (up to 96 Weeks) |
|
|
Analysis was performed on all randomized population.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/Lademirsen | Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period. Participants who received placebo and completed DB treatment period entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96). |
| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| eGFR value | 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. age=years, calculated at time of creatinine measurement. | Mean | Standard Deviation | mL/min/1.73m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Analysis was performed on safety population that included all participants who received at least one dose or partial of a dose of the IMP, analyzed according to the treatment actually received. | Posted | Count of Participants | Participants | 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) |
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| Primary | 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. | Analysis was performed on primary population that included all randomized participants who completed the double-blinded period (the first 48 weeks) or discontinued double-blinded period early. | Posted | Least Squares Mean | Standard Error | mL/min/1.73 m^2/year | Baseline, Week 48 |
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| Secondary | 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. | Analysis was performed on Intent-to-Treat (ITT) population that included all randomized participants analyzed according to the treatment group allocated by randomization. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Least Squares Mean | Standard Error | mL/min/1.73 m^2 | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Least Squares Mean | Standard Error | percent change | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'number analyzed' = participants considered for the analysis for each specified category. | Posted | Count of Participants | Participants | At Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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. | Analysis was performed on safety population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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. | Analysis was performed on safety population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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. | Analysis was performed on safety population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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. | Analysis was performed on safety population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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. | Analysis was performed on safety population. | Posted | Count of Participants | Participants | From Baseline up to Week 48 |
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| Secondary | 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). | Analysis was performed on PK population that included all participants who received at least one dose of IMP and had at least one post-dose PK sample. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo arm. | Posted | Mean | Standard Deviation | nanograms per milliliter | Post-dose (4 hours) on Day 1, Weeks 24 and 48 |
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| Secondary | 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). | Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo arm. | Posted | Mean | Standard Deviation | nanograms per milliliter | Pre-dose (up to 4 hours before study drug administration) on Weeks 4, 12, 24, 36 and 48 |
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| Secondary | 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. | Analysis was performed on ADA population that included all randomized participants who received at least one dose of study drugs and had at least one post-baseline ADA sample. | Posted | Count of Participants | Participants | 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) |
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| Secondary | 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. | Analysis was performed on ADA population. For this outcome measure analysis was done separately for TE-ADA positive and negative participants for placebo and lademirsen arms respectively. Here, "0" in the "overall number of participants analyzed" signifies that no participants had ADA positive response in the placebo arm. | Posted | Count of Participants | Participants | 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) |
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| Secondary | DB Period: Change From Baseline in Circulating MicroRNA-21 at Weeks 24 and 48 | Circulating microRNA-21 were the supportive biomarkers assessed in study. | Data for this outcome measure could not be analyzed and reported as the samples for circulating microRNA-21 at the predefined timepoints, Weeks 24 and 48 were not collected and analyzed due to early study termination. | Posted | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | milligrams per deciliter (mg/dL) | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | micrograms per liter (mcg/L) | Baseline, Weeks 24 and 48 |
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| Secondary | 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. | Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Mean | Standard Deviation | ratio | Baseline, Weeks 24 and 48 |
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DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106)
Analysis was performed on safety population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DB Period: Placebo | Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period. | 0 | 14 | 0 | 14 | 14 | 14 |
| EG001 | DB Period: Lademirsen | Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. | 0 | 29 | 2 | 29 | 29 | 29 |
| EG002 | OLE Period: Placebo/Lademirsen | Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96). | 0 | 9 | 2 | 9 | 8 | 9 |
| EG003 | OLE Period: Lademirsen/Lademirsen | Participants who completed DB treatment period with lademirsen 110 mg QW, 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). | 0 | 19 | 1 | 19 | 19 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory Tract Infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Complex Regional Pain Syndrome | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Blood Creatinine Increased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Glomerular Filtration Rate Decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Hand Fracture | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Covid-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis Salmonella | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Tooth Abscess | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Allergic Eosinophilia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nephrogenic Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperchloraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Iron Deficiency | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Metabolic Acidosis | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vitamin B12 Deficiency | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vitamin D Deficiency | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Burning Sensation | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ophthalmic Migraine | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dry Eye | Eye disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Periorbital Swelling | Eye disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ear Pain | Ear and labyrinth disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Asthmatic Crisis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nasal Obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Anal Incontinence | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Gastrointestinal Disorder | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Mouth Ulceration | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Plicated Tongue | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Rash Erythematous | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Skin Discolouration | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Joint Laxity | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Muscle Contracture | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
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| Urinary Incontinence | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
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| Menstruation Delayed | Reproductive system and breast disorders | MedDRA 25.0 | Systematic Assessment |
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| Ovarian Cyst | Reproductive system and breast disorders | MedDRA 25.0 | Systematic Assessment |
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| Ovarian Cyst Ruptured | Reproductive system and breast disorders | MedDRA 25.0 | Systematic Assessment |
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| Vaginal Haemorrhage | Reproductive system and breast disorders | MedDRA 25.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Chills | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Feeling Abnormal | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection Site Bruising | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection Site Erythema | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection Site Haemorrhage | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection Site Pain | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Injection Site Reaction | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Vessel Puncture Site Bruise | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Blood Bicarbonate Decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Blood Parathyroid Hormone Increased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Blood Pressure Increased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Glomerular Filtration Rate Decreased | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Heart Rate Irregular | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Sars-Cov-2 Test Positive | Investigations | MedDRA 25.0 | Systematic Assessment |
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| Accidental Overdose | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Back Injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Head Injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Joint Injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Ligament Sprain | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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Due to early study termination, Stage 2/Cohort 2 was not conducted. In Stage 1 analysis of DB period was performed until 48 weeks. In Stage 1 OL period, only safety data was collected and assessed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi-Aventis Recherche & Développement | 800-633-1610 | 6# | Contact-US@sanofi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2022 | Sep 8, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D009394 | Nephritis, Hereditary |
| D007674 | Kidney Diseases |
| D009393 | Nephritis |
| ID | Term |
|---|---|
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| Early study termination by sponsor |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| TESAE |
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Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.
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Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period. ADA positive were participants with treatment induced or treatment boosted ADAs that occurred at any time after the first administration of IMP during the DB treatment period. |
| OG001 | Placebo: TE-ADA Negative | Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period. ADA negative were participants with neither treatment induced nor treatment boosted ADAs at all time after the first administration of IMP during the DB treatment period. |
| OG002 | Lademirsen: TE-ADA Positive | Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. ADA positive were participants with treatment induced or treatment boosted ADAs that occurred at any time after the first administration of IMP during the DB treatment period. |
| OG003 | Lademirsen: TE-ADA Negative | Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. ADA negative were participants with neither treatment induced nor treatment boosted ADAs at all time after the first administration of IMP during the DB treatment period. |
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