The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in infants and young children with confirmed primary hyperoxaluria type 1 (PH1).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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
Lyon, France
Clinical Trial Site
Paris, France
Percentage 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.
Time frame: Baseline to Month 6
Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60])
A negative change from baseline indicates a favorable outcome.
Time frame: From Month 6 to Month 60
Percentage of Time That Spot Urinary Oxalate: Creatinine Ratio is at or Below the Near-normalization Threshold (≤1.5 × Upper Limit of Normal (ULN) for Age)
Percentage of time that spot urinary oxalate: creatinine (UOx:Cr) ratio level is at or below ≤ 1.5xULN is calculated as (cumulative months at or below near normalization threshold divided by cumulative months of assessments)\*100. Cumulative months in near-normalization is defined as the summation across all intervals that met the near-normal threshold and cumulative months of valid assessments is defined as the summation across all valid post-baseline collections. ULN levels of spot urinary oxalate to creatinine ratio where urine oxalate levels were analyzed using enzymatic assay. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.
Time frame: Up to 60 months
Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline
The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine.
Time frame: From Baseline to Month 6 and Month 60
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Clinical Trial Site
Bonn, Germany
Clinical Trial Site
Haifa, Israel
Clinical Trial Site
Jerusalem, Israel
Clinical Trial Site
Nahariya, Israel
Clinical Trial Site
London, United Kingdom
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age
The percentage of participants meeting the criteria (UOx:Cr ratio ≤ the ULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.
Time frame: Up to 60 months
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age
The percentage of participants meeting the criteria (UOx:Cr ratio ≤ 1.5xULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073.
Time frame: Up to 60 months
Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60)
The lower limit of quantification (LLOQ) was 5.55 micromoles per liter (μmol/L). A negative change from baseline indicates a favorable outcome.
Time frame: From Baseline to Month 6 and Month 60
Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60)
The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome.
Time frame: From Baseline to Month 6 and Month 60
Maximum Observed Plasma Concentration (Cmax) of Lumasiran
Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran
Tmax was estimated by calculating the time required to reach the maximum plasma concentration (Cmax) after the drug administration. Lower Tmax generally indicates faster drug absorption from the administration site.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Elimination Half-life (t1/2beta) of Lumasiran
Elimination half-life was estimated from the terminal phase of the plasma concentration-time profile post-dose. Shorter half-life generally indicates rapid drug elimination from the body.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran
AUC0-24 was the total drug exposure calculated as the area under the plasma concentration-time curve from the time of dosing (t = 0) to 24 hours.
Time frame: 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran
AUC0-last was the total drug exposure calculated as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (quantifiable) concentration (C\_last).
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran
AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Apparent Clearance (CL/F) of Lumasiran
Apparent clearance was calculated by dividing the area under the plasma concentration-time curve from zero infinity by the dose administered. A higher clearance generally indicates faster elimination from the body.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Apparent Volume of Distribution (V/F) of Lumasiran
Apparent Volume of Distribution generally indicates the extent of drug distribution in the body.
Time frame: 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
eGFR \[in milliliters per minute per 1.73 meters square (mL/min/1.73m\^2)\] was calculated from serum creatinine (SCr) based on the Schwartz Bedside Formula for participants ≥12 months of age at the time of assessment.
Time frame: From Baseline to Month 6 and Month 60
Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Time frame: Up to 60 months