The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in patients with Advanced Primary Hyperoxaluria Type 1 (PH1).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Lumasiran will be administered by subcutaneous (SC) injection.
Clinical Trial Site
Rochester, Minnesota, United States
Clinical Trial Site
Houston, Texas, United States
Clinical Trial Site
Garran, Australia
Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran.
Time frame: Baseline to Month 6
Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6
Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort B, the baseline is defined as the mean of the last four pre-dialysis plasma oxalate samples collected prior to the first dose of lumasiran. In Cohort B, only pre-dialysis samples are utilized.
Time frame: Baseline to Month 6
Cohort B: Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 6
Percent change in plasma oxalate AUC(0-24) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean value of all valid AUC (μmol/L/24h) profiles being computed prior to the first dose of lumasiran.
Time frame: Baseline to Month 6
Absolute Change in Plasma Oxalate From Baseline to Month 6
Absolute change in plasma oxalate was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. For Cohort A, the baseline was defined as the mean of all plasma oxalate level values collected prior to the first dose of lumasiran; for Cohort B, the baseline was defined as the mean of the last 4 pre-dialysis plasma oxalate level values collected prior to the first dose of lumasiran. In Cohort B patients, the plasma oxalate baseline was similarly defined except that the values obtained from the plasma oxalate profile assessment visits only included the pre-dialysis sample collected per visit.
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Clinical Trial Site
Brussels, Belgium
Clinical Trial Site
Bron, France
Clinical Trial Site
Lyon, France
Clinical Trial Site
Haifa, Israel
Clinical Trial Site
Nahariya, Israel
Clinical Trial Site
Rome, Italy
Clinical Trial Site
Irbid, Jordan
...and 4 more locations
Time frame: Baseline to Month 6
Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome. Baseline is defined as the median of all valid 24-hr urine assessments collected prior to the first dose date/time of lumasiran without any non-protocol-related sample issues.
Time frame: Baseline to Month 6
Cohort A: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome. Baseline is defined as the mean of all assessments prior to the first dose date/time of lumasiran.
Time frame: Baseline to Month 6
Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Absolute change in spot urinary oxalate:creatinine ratio was estimated by an average absolute change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean of all assessments prior to the first dose date/time of lumasiran.
Time frame: Baseline to Month 6
Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Baseline was defined as the mean of all assessments prior to the first dose date/time of lumasiran.
Time frame: Baseline to Month 6
Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score From Baseline to Month 6 in Patients >=2 to 18 Years of Age at Time of Informed Consent
Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are ≥2 to \<18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.
Time frame: Baseline to Month 6
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 6 in Patients ≥18 Years of Age at Time of Informed Consent
The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are ≥18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.
Time frame: Baseline to Month 6
Maximum Plasma Concentration (Cmax) of Lumasiran
Cmax is the highest concentration of lumasiran in the plasma after a dose is given.
Time frame: Day 1; Month 6
Time to Maximum Plasma Concentration (Tmax) of Lumasiran
Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration.
Time frame: Day 1; Month 6
Elimination Half-life (t½β) of Lumasiran
t½β is the time it takes for the concentration of the drug in the plasma to be reduced by 50%.
Time frame: Day 1; Month 6
Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran
AUC(0-24) is the area under the plasma concentration-time curve over the last 24-h dosing interval.
Time frame: Day 1; Month 6
Apparent Clearance (CL/F) of Lumasiran
CL/F is the rate at which lumasiran is eliminated from the body.
Time frame: Day 1; Month 6
Apparent Volume of Distribution (V/F) of Lumasiran
V/F is the propensity of lumasiran to either remain in the plasma or redistribute to other tissues.
Time frame: Day 1; Month 6
Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60
Time frame: Baseline to Month 60
Absolute Change in Plasma Oxalate From Baseline to Month 60
Time frame: Baseline to Month 60
Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Time frame: Baseline to Month 60
Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
Time frame: Baseline to Month 60
Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Time frame: Baseline to Month 60
Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
Time frame: Baseline to Month 60
Change in Quality of Life As Assessed by Pediatric Quality of Life Inventory (PedsQL) Total Score From Baseline to Month 60 in Patients >=2 to 18 Years of Age at Time of Informed Consent
Peds-QL is a modular approach to measuring quality of life (QOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL Generic Core Scales contain 23 items designed to measure core domains of health (physical, emotional, and social functioning) and role (school functioning). Scores are summarized as Total Scale Score, Physical Health Summary Score, and Psychosocial Health Summary Score. The Total Scale Score will be reported for this study. The PedsQL will be completed by patients (or caregivers, as appropriate) who are ≥2 to \<18 years of age at the time of consent. Total score range: 0 - 100, with higher scores indicating better health-related quality of life (HRQoL). Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.
Time frame: Baseline to Month 60
Change in Quality of Life As Assessed by Kidney Disease and Quality of Life (KDQOL) Scores From Baseline to Month 60 in Patients ≥18 Years of Age at Time of Informed Consent
The KDQOL questionnaire is used to assess 3 core domains of kidney disease including: burden, symptoms/problems, and effects of kidney disease on daily life. The KDQOL subscales (Burden of Kidney Disease, Effect of Kidney Disease on Daily Life, and Symptoms and Problems of Kidney Disease), and the accompanying Short Form-12 (SF-12) Physical Component Summary and Mental Component Summary will be assessed for this study. These will be completed by patients who are ≥18 years of age at the time of consent. Score range (per domain): 0 - 100; higher scores indicate better HRQoL. Baseline is defined as last non-missing value collected prior to the first dose of lumasiran.
Time frame: Baseline to Month 60
Percent Change in Plasma Oxalate From Baseline to End of Study
Time frame: Baseline to Month 60
Change in Nephrocalcinosis From Baseline to End of Study
Nephrocalcinosis will be assessed by renal ultrasound.
Time frame: Baseline to Month 60
Change in Frequency of Dialysis From Baseline to End of Study
Time frame: Baseline to Month 60
Change in Mode of Dialysis From Baseline to End of Study
Modes of dialysis are defined as hemodialysis and peritoneal dialysis.
Time frame: Baseline to Month 60
Change in Frequency of Renal Stone Events From Baseline to End of Study
Time frame: Baseline to Month 60
Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study
Time frame: Baseline to Month 60
Change in Measures of Systemic Oxalosis From Baseline to End of Study
Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems.
Time frame: Baseline to Month 60