Clinical trial NCT04152200: A Study to Evaluate Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1
Official title: ILLUMINATE-C: A Single Arm Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Lumasiran in Patients With Advanced Primary Hyperoxaluria Type 1 (PH1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Hyperoxaluria Type 1
Primary Hyperoxaluria
Keywords: PH1
Primary Hyperoxaluria
Hyperoxaluria
RNAi Therapeutic
siRNA
AGT
Systemic Oxalosis
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-05
Enrollment: 21
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Cohort A: Percent Change in Plasma Oxalate From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Cohort B: Percent Change in Pre-dialysis Plasma Oxalate From Baseline to Month 6
timeFrame: Baseline to Month 6
Secondary outcomes:
measure: 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
timeFrame: Baseline to Month 6
measure: Absolute Change in Plasma Oxalate From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Cohort A: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Cohort A: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Cohort A: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: Cohort A: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
timeFrame: Baseline to Month 6
measure: 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
timeFrame: Baseline to Month 6
measure: 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
timeFrame: Baseline to Month 6
measure: Maximum Plasma Concentration (Cmax) of Lumasiran
timeFrame: Day 1; Month 6
measure: Time to Maximum Plasma Concentration (Tmax) of Lumasiran
timeFrame: Day 1; Month 6
measure: Elimination Half-life (t½β) of Lumasiran
timeFrame: Day 1; Month 6
measure: Area Under the Concentration-time Curve From 0 to 24 Hours [AUC(0-24)] for Lumasiran
timeFrame: Day 1; Month 6
measure: Apparent Clearance (CL/F) of Lumasiran
timeFrame: Day 1; Month 6
measure: Apparent Volume of Distribution (V/F) of Lumasiran
timeFrame: Day 1; Month 6
measure: Percent Change in Plasma Oxalate Area Under the Curve From 0-24 Hours [AUC(0-24)] Between Dialysis Sessions From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: Absolute Change in Plasma Oxalate From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: Absolute Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: Percent Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 60
timeFrame: Baseline to Month 60
measure: 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
timeFrame: Baseline to Month 60
measure: 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
timeFrame: Baseline to Month 60
measure: Percent Change in Plasma Oxalate From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Nephrocalcinosis From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Frequency of Dialysis From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Mode of Dialysis From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Frequency of Renal Stone Events From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Renal Function Assessed by Estimated Glomerular Filtration Rate (eGFR) From Baseline to End of Study
timeFrame: Baseline to Month 60
measure: Change in Measures of Systemic Oxalosis From Baseline to End of Study
timeFrame: Baseline to Month 60
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Garran
country: Australia
facility: Clinical Trial Site
city: Brussels
country: Belgium
facility: Clinical Trial Site
city: Bron
country: France
facility: Clinical Trial Site
city: Lyon
country: France
facility: Clinical Trial Site
city: Haifa
country: Israel
facility: Clinical Trial Site
city: Nahariya
country: Israel
facility: Clinical Trial Site
city: Rome
country: Italy
facility: Clinical Trial Site
city: Irbid
country: Jordan
facility: Clinical Trial Site
city: Beirut
country: Lebanon
facility: Clinical Trial Site
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: Yenimahalle
country: Turkey
facility: Clinical Trial Site
city: Dubai
country: United Arab Emirates
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Michael M, Groothoff JW, Shasha-Lavsky H, Lieske JC, Frishberg Y, Simkova E, Sellier-Leclerc AL, Devresse A, Guebre-Egziabher F, Bakkaloglu SA, Mourani C, Saqan R, Singer R, Willey R, Habtemariam B, Gansner JM, Bhan I, McGregor T, Magen D. Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial. Am J Kidney Dis. 2023 Feb;81(2):145-155.e1. doi: 10.1053/j.ajkd.2022.05.012. Epub 2022 Jul 14.