Phase 3
N=21
A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1
Primary Hyperoxaluria Type 1 · Primary Hyperoxaluria
Bottom Line
View on ClinicalTrials.gov: NCT04152200 ↗Enrolled (actual)
21
Serious AEs
42.9%
Results posted
Jul 2022
Primary outcome: Primary: Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6 — -33.33 percent change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Lumasiran (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Alnylam Pharmaceuticals
- Primary completion
- May 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6 |
-33.33 | — |
| PRIMARY Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6 |
-42.43 | — |
| 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 |
-41.4 | — |
| SECONDARY Absolute Change in Plasma Oxalate From Baseline to Month 6 |
-35.28; -48.33 | — |
| SECONDARY Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6 |
-0.533 | — |
| SECONDARY Cohort A: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6 |
-10.557 | — |
| SECONDARY Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 |
-0.1879 | — |
| SECONDARY Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 |
-39.5136 | — |
| 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 |
-23.91; 0.10 | — |
| 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 |
-1.56; -2.06; -3.88; 1.58; -13.64; -5.73 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Lumasiran |
1019.9; 1820.5; 1542.8; 1038.2; 1289.3; 1211.9 | — |
| SECONDARY Time to Maximum Plasma Concentration (Tmax) of Lumasiran |
3.8083; 4.0000; 4.0000; 3.9083; 4.0167; 4.0000 | — |
| SECONDARY Elimination Half-life (t½β) of Lumasiran |
9.0246; 3.6670; 3.8302; 8.1069; 4.5131; 5.7484 | — |
| SECONDARY Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran |
13156.8031; 13170.3716; 13164.1075; 11417.0267; 20647.6317; 14856.4905 | — |
| SECONDARY Apparent Clearance (CL/F) of Lumasiran |
7.8440; 5.1003; 5.7356; 4.8496; 6.8556; 5.9104 | — |
| SECONDARY Apparent Volume of Distribution (V/F) of Lumasiran |
77.5329; 25.7429; 34.7734; 41.7081; 36.8305; 38.8468 | — |
| 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 |
— | — |
| SECONDARY Absolute Change in Plasma Oxalate From Baseline to Month 60 |
— | — |
| SECONDARY Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 |
— | — |
| SECONDARY Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60 |
— | — |
| SECONDARY Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 |
— | — |
| SECONDARY Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60 |
— | — |
| 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 |
— | — |
| 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 |
— | — |
| SECONDARY Percent Change in Plasma Oxalate From Baseline to End of Study |
— | — |
| SECONDARY Change in Nephrocalcinosis From Baseline to End of Study |
— | — |
| SECONDARY Change in Frequency of Dialysis From Baseline to End of Study |
— | — |
| SECONDARY Change in Mode of Dialysis From Baseline to End of Study |
— | — |
| SECONDARY Change in Frequency of Renal Stone Events From Baseline to End of Study |
— | — |
| SECONDARY Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study |
— | — |
| SECONDARY Change in Measures of Systemic Oxalosis From Baseline to End of Study |
— | — |
Summary
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).
Eligibility Criteria
Inclusion Criteria
- Has documented diagnosis of primary hyperoxaluria type 1 (PH1)
- Estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m^2 for patients ≥12 months of age (<12 months of age, must have serum creatinine considered elevated for age)
- Meets plasma oxalate level requirements
- If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
- If on dialysis, may be on hemodialysis therapy only and must have been on a stable regimen for at least 4 weeks
Exclusion Criteria
- Hemodialysis/peritoneal dialysis combination therapy or peritoneal dialysis alone
- Diagnosis of conditions other than PH1 contributing to renal insufficiency
- History of liver transplant
- History of kidney transplant and currently receiving immunosuppressants
Data sourced from ClinicalTrials.gov (NCT04152200). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.