| Primary | 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. | Full Analysis Set (FAS): All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | percent change | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| Restricted maximum likelihood (REML) based Mixed Model Repeated Measures (MMRM) was used to test against the null hypothesis of mean change from baseline outcome being equal to 0. The model includes scheduled visits and baseline plasma oxalate (μmol/L) as fixed effects and patient as a random factor. Autoregressive (1) was used to model the within-patient variability. | Mixed model repeated measures (MMRM) | | | | Least Squares (LS) Mean | -33.33 | Standard Error of the Mean | 17.63 | 2-Sided | 95 | -81.82 | 15.16 | | | | | Other | |
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| Primary | 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. | FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | percent change | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort B: Lumasiran | Patients on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | percent change | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort B: Lumasiran | Patients on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | μmol/L | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran (with data available for analysis) and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. No analyses were performed for patients in Cohort B that were anuric (ie, patients able to continue to produce urine ≥100 mL per day). | Posted | | Least Squares Mean | Standard Error | mmol/24hr/1.73m^2 | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran (with data available for analysis) and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. No analyses were performed for patients in Cohort B that were anuric (ie, patients able to continue to produce urine ≥100 mL per day). | Posted | | Least Squares Mean | Standard Error | percent change | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | ratio | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | FAS: All patients who received any amount of lumasiran and had at least 1 evaluable plasma oxalate value (pre-dialysis in Cohort B) at baseline and at least 1 evaluable plasma oxalate value from assessment(s) at Month 3 through Month 6. | Posted | | Least Squares Mean | Standard Error | percent change | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | Participants from the FAS who were ≥2 to <18 years of age at the time of consent with data available for analysis. | Posted | | Mean | Standard Deviation | score on a scale | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | Participants from the FAS who were ≥18 years of age at the time of consent. | Posted | | Mean | Standard Deviation | score on a scale | | Baseline to Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | Maximum Plasma Concentration (Cmax) of Lumasiran | Cmax is the highest concentration of lumasiran in the plasma after a dose is given. | Pharmacokinetic (PK) Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | Time to Maximum Plasma Concentration (Tmax) of Lumasiran | Tmax is the time it takes for lumasiran to reach the maximum concentration (Cmax) after administration. | PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data. | Posted | | Median | Full Range | hours | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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%. | PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint. | Posted | | Median | Full Range | hours | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | Apparent Clearance (CL/F) of Lumasiran | CL/F is the rate at which lumasiran is eliminated from the body. | PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liters/hour (L/h) | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | 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. | PK Analysis Set: All patients who received any amount of lumasiran, have at least 1 postdose blood sample for PK parameters, and have evaluable PK data at the given timepoint. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Liters (L) | | Day 1; Month 6 | | | | ID | Title | Description |
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| OG000 | Cohort A: Lumasiran | Patients not on dialysis received open-label lumasiran based on weight. Patients weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg monthly during the 6-month primary analysis period and monthly during the 54-month extension period. Patients in maintenance dosing who transitioned from <10 kg to ≥10 kg continued to receive monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for patients weighing ≥10 kg. Thereafter, patients followed every-3-months dosing until the end of the study. Patients weighing ≥10 to <20 kg received loading doses of lumasiran SC injection 6.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 6.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients weighing ≥20 kg received loading doses of lumasiran SC injection 3.0 mg/kg monthly for 3 months, followed by maintenance doses of lumasiran SC injection 3.0 mg/kg at Months 3 and 6 in the 6-month primary analysis period and every three months during the 54-month extension period. Patients with weight increases crossing the threshold for the next weight-based dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new dosing regimen for the remainder of the study or until the next dosing category threshold was reached. |
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| Secondary | Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Absolute Change in Plasma Oxalate From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | 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. | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | 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. | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Percent Change in Plasma Oxalate From Baseline to End of Study | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Nephrocalcinosis From Baseline to End of Study | Nephrocalcinosis will be assessed by renal ultrasound. | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Frequency of Dialysis From Baseline to End of Study | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Mode of Dialysis From Baseline to End of Study | Modes of dialysis are defined as hemodialysis and peritoneal dialysis. | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Frequency of Renal Stone Events From Baseline to End of Study | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study | | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |
| Secondary | Change in Measures of Systemic Oxalosis From Baseline to End of Study | Systemic oxalosis will be assessed in cardiac, skeletal, ophthalmologic, and dermatologic systems. | | Not Posted | | | | | | Baseline to Month 60 | | Participants | | | | |