A Study of Lumasiran in Infants and Young Children With Primary Hyperoxaluria Type 1
- Conditions
- Primary HyperoxaluriaPrimary Hyperoxaluria Type 1 (PH1)
- Interventions
- Registration Number
- NCT03905694
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- Has genetic confirmation of primary hyperoxaluria type 1 (PH1)
- Meets urinary oxalate excretion requirements
- If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
- If <12 months old at screening, has an abnormally high serum creatinine
- If ≥12 months old at screening, has an estimated glomerular filtration rate (GFR) of ≤45 mL/min/1.73m^2
- Clinical evidence of systemic oxalosis
- History of kidney or liver transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lumasiran Lumasiran Lumasiran will be administered by subcutaneous (SC) injection.
- Primary Outcome Measures
Name Time Method Percentage Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 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.
- Secondary Outcome Measures
Name Time Method Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60]) From Month 6 to Month 60 A negative change from baseline indicates a favorable outcome.
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) Up to 60 months 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.
Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline From Baseline to Month 6 and Month 60 The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine.
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age Up to 60 months 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.
Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age Up to 60 months 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.
Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60) From Baseline to Month 6 and 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.
Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60) From Baseline to Month 6 and Month 60 The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome.
Maximum Observed Plasma Concentration (Cmax) of Lumasiran 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 Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure.
Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran 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 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.
Elimination Half-life (t1/2beta) of Lumasiran 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 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.
Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 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.
Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran 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 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).
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran 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 AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity.
Apparent Clearance (CL/F) of Lumasiran 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 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.
Apparent Volume of Distribution (V/F) of Lumasiran 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 generally indicates the extent of drug distribution in the body.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Month 6 and Month 60 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.
Number of Participants With Adverse Events (AEs) Up to 60 months 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.
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧London, United Kingdom